FLT3
gene geneOn this page
Also known as STK1FLK2CD135
Summary
FLT3 (fms related receptor tyrosine kinase 3, HGNC:3765) is a protein-coding gene on chromosome 13q12.2, encoding Receptor-type tyrosine-protein kinase FLT3 (P36888). Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells. In precision oncology, FLT3 ITD confers sensitivity to Gilteritinib in Acute Myeloid Leukemia (CIViC Level A); 80 further curated variant–drug associations are listed below.
This gene encodes a class III receptor tyrosine kinase that regulates hematopoiesis. This receptor is activated by binding of the fms-related tyrosine kinase 3 ligand to the extracellular domain, which induces homodimer formation in the plasma membrane leading to autophosphorylation of the receptor. The activated receptor kinase subsequently phosphorylates and activates multiple cytoplasmic effector molecules in pathways involved in apoptosis, proliferation, and differentiation of hematopoietic cells in bone marrow. Mutations that result in the constitutive activation of this receptor result in acute myeloid leukemia and acute lymphoblastic leukemia.
Source: NCBI Gene 2322 — RefSeq curated summary.
At a glance
- Gene–disease (curated): leukemia, acute myeloid, susceptibility to (Limited, ClinGen)
- GWAS associations: 63 (top 1% of genes corpus-wide)
- Clinical variants (ClinVar): 247 total — 10 pathogenic, 4 likely-pathogenic
- GTEx eGene: eQTL in 33 tissues, sQTL in 1 (q < 0.05)
- Phenotypes (HPO): 5
- Drug target: yes — 39 curated mechanism-of-action drugs; 143 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
- Approved drugs (ChEMBL mechanism of action): 8 — Fedratinib, Gilteritinib, Midostaurin, +5 more
- Precision-oncology evidence (CIViC): 81 curated variant–drug associations
- Cancer driver (intOGen): activating (oncogene-like) across 2 cancer types (inferred from mutation patterns)
- Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.47 (moderately constrained)
- Transcription factor: yes — 19 downstream targets (CollecTRI)
- MANE Select transcript:
NM_004119 - Interaction hub: 2,904 STRING partners (top 3% of genes corpus-wide)
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:3765 |
| Approved symbol | FLT3 |
| Name | fms related receptor tyrosine kinase 3 |
| Location | 13q12.2 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | STK1, FLK2, CD135 |
| Ensembl gene | ENSG00000122025 |
| Ensembl biotype | protein_coding |
| OMIM | 136351 |
| Entrez | 2322 |
Gene structure
Transcript identifiers
Ensembl transcripts: 6 — 3 protein_coding, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined
MANE Select: ENST00000241453
Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 3: 1
ENST00000241453, ENST00000380987, ENST00000469894, ENST00000864668, ENST00001004561, ENST00001131816
RefSeq mRNA: 1 — MANE Select: NM_004119
NM_004119
CCDS: CCDS31953
Canonical transcript exons
ENST00000241453 — 24 exons
| Exon | Start | End |
|---|---|---|
| ENSE00000827401 | 28037185 | 28037288 |
| ENSE00000827402 | 28035935 | 28036043 |
| ENSE00000827403 | 28035495 | 28035673 |
| ENSE00000827404 | 28034301 | 28034407 |
| ENSE00000827405 | 28034082 | 28034214 |
| ENSE00000827406 | 28033887 | 28033991 |
| ENSE00000827407 | 28028178 | 28028288 |
| ENSE00000827408 | 28027088 | 28027241 |
| ENSE00000906608 | 28048275 | 28048443 |
| ENSE00000906609 | 28049384 | 28049537 |
| ENSE00000906610 | 28049635 | 28049774 |
| ENSE00000906611 | 28050095 | 28050222 |
| ENSE00000906612 | 28052545 | 28052674 |
| ENSE00000906613 | 28057347 | 28057462 |
| ENSE00000906614 | 28061867 | 28062069 |
| ENSE00000906615 | 28070491 | 28070612 |
| ENSE00001487116 | 28003274 | 28004174 |
| ENSE00003513156 | 28014452 | 28014557 |
| ENSE00003519436 | 28023350 | 28023477 |
| ENSE00003552851 | 28015590 | 28015701 |
| ENSE00003565636 | 28024861 | 28024943 |
| ENSE00003598146 | 28018467 | 28018589 |
| ENSE00003692016 | 28015157 | 28015256 |
| ENSE00003896396 | 28100468 | 28100576 |
Expression profiles
Bgee: expression breadth ubiquitous, 166 present calls, max score 86.25.
FANTOM5 (CAGE): breadth broad, TPM avg 2.7806 / max 577.0111, expressed in 297 samples.
Highest expression (Bgee): male germ line stem cell (sensu Vertebrata) in testis, cerebellar hemisphere, cerebellar cortex, monocyte, mononuclear cell.
Genetic regulation across tissues (GTEx eQTL / sQTL)
FLT3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 33 tissues and its splicing (sQTL) in 1 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.
showing 20 of 34 significant tissue × QTL associations:
| Tissue | QTL | q-value | Slope | Lead variant |
|---|---|---|---|---|
| Brain Cerebellum | eqtl | 1.9e-71 | +1.21 | 13:28027857:G:A |
| Brain Cerebellar Hemisphere | eqtl | 4.6e-67 | +1.21 | 13:28027514:T:C |
| Brain Cortex | eqtl | 6.8e-51 | +1.00 | 13:28027514:T:C |
| Brain Anterior cingulate cortex BA24 | eqtl | 2.6e-38 | +0.94 | 13:28033573:G:C |
| Brain Frontal Cortex BA9 | eqtl | 2.1e-36 | +1.00 | 13:28033573:G:C |
| Pancreas | eqtl | 3.2e-25 | -0.75 | 13:28086023:T:A |
| Skin Sun Exposed Lower leg | eqtl | 1.0e-22 | +0.39 | 13:28028119:C:T |
| Brain Hypothalamus | eqtl | 1.1e-20 | +0.69 | 13:28028467:T:C |
| Skin Not Sun Exposed Suprapubic | eqtl | 1.8e-13 | +0.34 | 13:28028119:C:T |
| Nerve Tibial | eqtl | 5.4e-11 | +0.33 | 13:28033573:G:C |
| Brain Putamen basal ganglia | eqtl | 6.0e-09 | +0.63 | 13:28031877:G:A |
| Brain Caudate basal ganglia | eqtl | 1.3e-08 | +0.64 | 13:28032042:T:A |
| Lung | eqtl | 1.5e-08 | +0.29 | 13:28018990:G:A |
| Brain Nucleus accumbens basal ganglia | eqtl | 2.1e-08 | +0.62 | 13:28027857:G:A |
| Brain Hippocampus | eqtl | 2.4e-08 | +0.54 | 13:28027857:G:A |
| Brain Spinal cord cervical c-1 | eqtl | 4.2e-08 | +0.46 | 13:28033380:T:C |
| Small Intestine Terminal Ileum | eqtl | 6.4e-08 | +0.40 | 13:28060647:T:C |
| Adipose Subcutaneous | eqtl | 7.5e-08 | -0.28 | 13:28037601:G:A |
| Esophagus Mucosa | eqtl | 4.4e-07 | +0.20 | 13:28020665:T:C |
| Spleen | eqtl | 9.1e-07 | +0.43 | 13:28027514:T:C |
FANTOM5 promoters
2 alternative TSS:
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 136527 | 2.7297 | 296 |
| 136526 | 0.0509 | 21 |
Top tissues by expression
showing 100 of 285 tissues by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| male germ line stem cell (sensu Vertebrata) in testis | CL:0000089 ∩ UBERON:0000473 | 86.25 | gold quality |
| cerebellar hemisphere | UBERON:0002245 | 81.49 | gold quality |
| cerebellar cortex | UBERON:0002129 | 81.37 | gold quality |
| monocyte | CL:0000576 | 81.07 | gold quality |
| mononuclear cell | CL:0000842 | 80.55 | gold quality |
| leukocyte | CL:0000738 | 80.03 | gold quality |
| right hemisphere of cerebellum | UBERON:0014890 | 80.01 | gold quality |
| cerebellum | UBERON:0002037 | 79.31 | gold quality |
| bone marrow cell | CL:0002092 | 73.72 | silver quality |
| bone marrow | UBERON:0002371 | 72.76 | gold quality |
| lymph node | UBERON:0000029 | 71.18 | gold quality |
| granulocyte | CL:0000094 | 70.09 | gold quality |
| body of pancreas | UBERON:0001150 | 69.61 | gold quality |
| spleen | UBERON:0002106 | 68.87 | gold quality |
| vermiform appendix | UBERON:0001154 | 68.31 | gold quality |
| C1 segment of cervical spinal cord | UBERON:0006469 | 67.90 | gold quality |
| gall bladder | UBERON:0002110 | 66.94 | gold quality |
| pancreas | UBERON:0001264 | 66.82 | gold quality |
| right lung | UBERON:0002167 | 66.38 | gold quality |
| blood | UBERON:0000178 | 66.37 | gold quality |
| pigmented layer of retina | UBERON:0001782 | 66.30 | gold quality |
| spinal cord | UBERON:0002240 | 65.24 | gold quality |
| caecum | UBERON:0001153 | 63.82 | gold quality |
| cerebellar vermis | UBERON:0004720 | 63.55 | silver quality |
| tibialis anterior | UBERON:0001385 | 63.36 | silver quality |
| islet of Langerhans | UBERON:0000006 | 62.86 | gold quality |
| rectum | UBERON:0001052 | 62.02 | gold quality |
| prefrontal cortex | UBERON:0000451 | 61.12 | gold quality |
| small intestine Peyer’s patch | UBERON:0003454 | 61.08 | gold quality |
| epithelial cell of pancreas | CL:0000083 | 59.89 | gold quality |
| upper leg skin | UBERON:0004262 | 59.81 | gold quality |
| nephron tubule | UBERON:0001231 | 59.24 | gold quality |
| small intestine | UBERON:0002108 | 59.09 | gold quality |
| smooth muscle tissue | UBERON:0001135 | 58.93 | gold quality |
| secondary oocyte | CL:0000655 | 58.77 | gold quality |
| right frontal lobe | UBERON:0002810 | 58.72 | gold quality |
| cingulate cortex | UBERON:0003027 | 58.32 | gold quality |
| anterior cingulate cortex | UBERON:0009835 | 58.04 | gold quality |
| primary visual cortex | UBERON:0002436 | 57.99 | gold quality |
| Brodmann (1909) area 9 | UBERON:0013540 | 57.98 | gold quality |
| neocortex | UBERON:0001950 | 57.43 | gold quality |
| frontal cortex | UBERON:0001870 | 57.42 | gold quality |
| colonic epithelium | UBERON:0000397 | 57.33 | silver quality |
| trabecular bone tissue | UBERON:0002483 | 57.07 | gold quality |
| hypothalamus | UBERON:0001898 | 56.70 | gold quality |
| decidua | UBERON:0002450 | 56.55 | gold quality |
| upper lobe of left lung | UBERON:0008952 | 56.51 | gold quality |
| renal glomerulus | UBERON:0000074 | 56.36 | silver quality |
| dorsolateral prefrontal cortex | UBERON:0009834 | 56.04 | gold quality |
| superficial temporal artery | UBERON:0001614 | 55.91 | gold quality |
| kidney epithelium | UBERON:0004819 | 55.86 | silver quality |
| mucosa of stomach | UBERON:0001199 | 55.85 | gold quality |
| pons | UBERON:0000988 | 55.84 | gold quality |
| tonsil | UBERON:0002372 | 55.35 | gold quality |
| upper lobe of lung | UBERON:0008948 | 55.12 | gold quality |
| paraflocculus | UBERON:0005351 | 54.62 | silver quality |
| skin of hip | UBERON:0001554 | 54.56 | gold quality |
| pancreatic ductal cell | CL:0002079 | 54.34 | silver quality |
| left uterine tube | UBERON:0001303 | 54.04 | gold quality |
| cerebral cortex | UBERON:0000956 | 53.92 | gold quality |
| cortical plate | UBERON:0005343 | 53.80 | gold quality |
| right testis | UBERON:0004534 | 53.72 | gold quality |
| left testis | UBERON:0004533 | 53.69 | gold quality |
| pleura | UBERON:0000977 | 53.65 | silver quality |
| right coronary artery | UBERON:0001625 | 53.64 | gold quality |
| occipital lobe | UBERON:0002021 | 53.62 | gold quality |
| transverse colon | UBERON:0001157 | 53.48 | gold quality |
| parietal pleura | UBERON:0002400 | 53.34 | silver quality |
| deltoid | UBERON:0001476 | 53.31 | gold quality |
| testis | UBERON:0000473 | 53.20 | gold quality |
| hair follicle | UBERON:0002073 | 53.13 | gold quality |
| intestine | UBERON:0000160 | 52.80 | gold quality |
| lung | UBERON:0002048 | 52.70 | gold quality |
| Brodmann (1909) area 46 | UBERON:0006483 | 52.20 | gold quality |
| central nervous system | UBERON:0001017 | 52.16 | gold quality |
| thymus | UBERON:0002370 | 52.14 | silver quality |
| substantia nigra | UBERON:0002038 | 52.08 | gold quality |
| brain | UBERON:0000955 | 51.73 | gold quality |
| ileal mucosa | UBERON:0000331 | 51.67 | silver quality |
| cortex of kidney | UBERON:0001225 | 51.20 | gold quality |
| midbrain | UBERON:0001891 | 51.03 | gold quality |
| colon | UBERON:0001155 | 50.99 | gold quality |
| visceral pleura | UBERON:0002401 | 50.90 | gold quality |
| muscle tissue | UBERON:0002385 | 50.86 | gold quality |
| quadriceps femoris | UBERON:0001377 | 50.82 | gold quality |
| large intestine | UBERON:0000059 | 50.77 | gold quality |
| minor salivary gland | UBERON:0001830 | 50.69 | gold quality |
| anatomical system | UBERON:0000467 | 50.66 | gold quality |
| material anatomical entity | UBERON:0000465 | 50.49 | gold quality |
| multicellular organism | UBERON:0000468 | 50.49 | gold quality |
| skin of leg | UBERON:0001511 | 50.47 | gold quality |
| frontal pole | UBERON:0002795 | 50.41 | gold quality |
| zone of skin | UBERON:0000014 | 50.33 | gold quality |
| middle frontal gyrus | UBERON:0002702 | 50.30 | gold quality |
| mucosa of transverse colon | UBERON:0004991 | 50.30 | gold quality |
| skin of abdomen | UBERON:0001416 | 50.28 | gold quality |
| Brodmann (1909) area 10 | UBERON:0013541 | 50.18 | gold quality |
| left coronary artery | UBERON:0001626 | 49.87 | gold quality |
| male germ cell | CL:0000015 | 49.86 | gold quality |
| esophagus mucosa | UBERON:0002469 | 49.84 | gold quality |
Single-cell (SCXA)
Detected in 5 experiment(s), a significant marker in 4.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-MTAB-6678 | yes | 171.14 |
| E-HCAD-6 | yes | 29.00 |
| E-ANND-3 | yes | 10.72 |
| E-MTAB-9801 | yes | 8.15 |
| E-GEOD-99795 | no | 21.87 |
HPA expression
RNA tissue specificity: Tissue enhanced
showing 60 of 68 HPA tissues / cells by nTPM:
| Tissue / cell | Axis | nTPM |
|---|---|---|
| Corpus callosum | tissue | 14.0 |
| Spinal cord | tissue | 12.6 |
| Pons | tissue | 12.5 |
| Midbrain | tissue | 12.5 |
| Medulla oblongata | tissue | 12.4 |
| Thalamus | tissue | 11.0 |
| Superior colliculi | tissue | 10.9 |
| Cerebellum | tissue | 10.1 |
| Substantia nigra | tissue | 8.8 |
| Periaqueductal gray | tissue | 7.7 |
| Hypothalamus | tissue | 7.6 |
| Lymph node | tissue | 6.1 |
| Cerebral cortex | tissue | 5.7 |
| Somatosensory cortex | tissue | 5.7 |
| Occipital cortex | tissue | 5.6 |
| Spleen | tissue | 5.3 |
| Bone marrow | tissue | 5.0 |
| Thymus | tissue | 4.3 |
| Septum | tissue | 4.3 |
| Ventral forebrain | tissue | 4.0 |
| Retrosplenial cortex | tissue | 4.0 |
| Hippocampal formation | tissue | 3.9 |
| Retrosplenial and cingulate cortex | tissue | 3.9 |
| Motor cortex | tissue | 3.8 |
| Prefrontal cortex | tissue | 3.5 |
| Tonsil | tissue | 3.4 |
| Olfactory bulb | tissue | 3.4 |
| Entorhinal cortex | tissue | 3.3 |
| Insular cortex | tissue | 3.3 |
| Temporal cortex | tissue | 3.0 |
| Amygdala | tissue | 2.8 |
| Appendix | tissue | 2.8 |
| Putamen | tissue | 2.7 |
| Pancreas | tissue | 2.6 |
| Postcentral gyrus | tissue | 2.0 |
| Locus coeruleus | tissue | 1.8 |
| Frontal cortex | tissue | 1.7 |
| Gallbladder | tissue | 1.5 |
| Breast | tissue | 1.4 |
| Kidney | tissue | 1.4 |
| Urinary bladder | tissue | 1.2 |
| Basal ganglia | tissue | 1.2 |
| Small intestine | tissue | 0.9 |
| Smooth muscle | tissue | 0.8 |
| Caudate putamen | tissue | 0.8 |
| Skin 1 | tissue | 0.7 |
| Rectum | tissue | 0.7 |
| Colon | tissue | 0.7 |
| Stomach 1 | tissue | 0.6 |
| Esophagus | tissue | 0.6 |
| Adipose tissue | tissue | 0.5 |
| Cervix | tissue | 0.4 |
| Testis | tissue | 0.4 |
| Choroid plexus | tissue | 0.4 |
| Lung | tissue | 0.4 |
| Liver | tissue | 0.4 |
| Nucleus accumbens | tissue | 0.3 |
| Seminal vesicle | tissue | 0.2 |
| Salivary gland | tissue | 0.2 |
| Endometrium 1 | tissue | 0.2 |
Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — White matter (14.0), Ventral spinal cord (12.6), Dorsal spinal cord (11.6), Cerebellar cortex (10.7), Flocculonodular lobe (9.6).
Regulation
Is transcription factor: yes
Downstream targets (CollecTRI)
19 targets:
| Target | Regulation |
|---|---|
| BCL2L1 | Activation |
| BCL2L11 | Repression |
| CDKN1A | Activation |
| CDKN1B | Repression |
| CEBPA | Unknown |
| CEBPB | Repression |
| CISH | Activation |
| FZD4 | Unknown |
| ID1 | Activation |
| PARP1 | Activation |
| PIM1 | Activation |
| PIM2 | Activation |
| PTPN6 | Unknown |
| RAD51 | Activation |
| SOCS2 | Activation |
| SOCS3 | Activation |
| SPI1 | Unknown |
| USP22 | Activation |
| XRCC5 | Activation |
Upstream regulators (CollecTRI, top): CEBPA, HES1, HOXA9, IKZF1, KAT6B, MEIS1, MYB, NCOR1, PAX5, PML, RUNX1, SPI1, STAT3, TXK
miRNA regulators (miRDB)
Targeting FLT3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).
showing 30 of 56 miRNAs:
| miRNA | Max score | Avg score | miRNA target_count |
|---|---|---|---|
| HSA-MIR-4533 | 100.00 | 69.48 | 2758 |
| HSA-MIR-518D-5P | 100.00 | 67.51 | 979 |
| HSA-MIR-518E-5P | 100.00 | 67.66 | 954 |
| HSA-MIR-518F-5P | 100.00 | 67.51 | 979 |
| HSA-MIR-519A-5P | 100.00 | 67.66 | 954 |
| HSA-MIR-519B-5P | 100.00 | 67.66 | 954 |
| HSA-MIR-519C-5P | 100.00 | 67.66 | 954 |
| HSA-MIR-520C-5P | 100.00 | 67.51 | 979 |
| HSA-MIR-522-5P | 100.00 | 67.66 | 954 |
| HSA-MIR-523-5P | 100.00 | 67.66 | 954 |
| HSA-MIR-526A-5P | 100.00 | 67.51 | 979 |
| HSA-MIR-3924 | 100.00 | 72.09 | 2394 |
| HSA-MIR-3163 | 100.00 | 77.23 | 8605 |
| HSA-MIR-1277-5P | 100.00 | 73.95 | 5056 |
| HSA-MIR-6798-5P | 100.00 | 65.77 | 699 |
| HSA-MIR-548C-3P | 99.99 | 74.01 | 7587 |
| HSA-MIR-520G-5P | 99.99 | 66.76 | 658 |
| HSA-MIR-548P | 99.98 | 72.25 | 3784 |
| HSA-MIR-570-3P | 99.96 | 72.41 | 4910 |
| HSA-MIR-497-5P | 99.92 | 71.83 | 2674 |
| HSA-MIR-15A-5P | 99.90 | 72.80 | 2787 |
| HSA-MIR-15B-5P | 99.90 | 72.78 | 2798 |
| HSA-MIR-16-5P | 99.90 | 72.80 | 2780 |
| HSA-MIR-195-5P | 99.90 | 72.81 | 2805 |
| HSA-MIR-4493 | 99.90 | 66.48 | 977 |
| HSA-MIR-424-5P | 99.89 | 71.90 | 2641 |
| HSA-MIR-6838-5P | 99.89 | 71.94 | 2690 |
| HSA-MIR-3140-3P | 99.88 | 68.47 | 2069 |
| HSA-MIR-4698 | 99.84 | 71.41 | 4303 |
| HSA-MIR-139-5P | 99.80 | 69.50 | 1399 |
Functional genomics
gnomAD constraint: pLI 0.997, LOEUF 0.468, missense Z 1.55 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD
Regional missense constraint (gnomAD RMC): no regional variation along ENST00000241453 — one region, missense o/e 0.90.
Literature-anchored findings (GeneRIF, showing 40)
- First report of D835X mutations in human. Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies. (PMID:11290608)
- Flt3/Flk-2-ligand in synergy with thrombopoietin may slow down megakaryocyte development by causing increased proliferation of megakaryocyte progenitor cells. (PMID:11983110)
- induces acute promyelocytic leukemia in a mouse model (PMID:12060771)
- Analysis of FLT3 length mutations in 1003 patients with acute myeloid leukemia (PMID:12070009)
- duplicated in relapsed acute myeloid leukemia (PMID:12239146)
- mutations occur in paired presentation and relapse samples from patients with acute myeloid leukemia (PMID:12239147)
- 767 of 6586 genes differed in expression between FLT3-WT- and FLT-ITD(internal tandem duplication)-expressing cell lines. ITD mutations of Flt3 activate transcriptional programs that partially mimic IL-3 activity. (PMID:12468433)
- Internal tandem duplication of the Flt3 gene appearing or altering at time of AML relapse suggests Flt3-gene abnormalities are very important in the pathogenesis of chemotherapy-resistant AML (PMID:12481903)
- The striking difference in flt3 and c-kit expression on hematopoietic stem cells translated into a corresponding difference in flt3 and c-kit function because FL was more efficient than SCF at supporting the survival of HSCs (PMID:12676789)
- Intracellular signaling initiated by Flt3 ligation modulates the functional phenotype for native human AML blasts both with and without genetic Flt3 abnormalities. (PMID:12681969)
- FLT3 mutations that lead to constitutive receptor activation and confer a poor prognosis in AML (PMID:12691136)
- FLT3/ITD is less common in pediatric than in adult acute myeloid leukemia and FLT3/ITD is a strong and independent adverse prognostic factor, and high ratios between mutant and WT-FLT3 further compromise prognosis. (PMID:12816873)
- antiapoptotic pathways from FLT3 with internal tandem duplication are more divergent than those from WtFLT3 (PMID:12842996)
- Mutations in the FLT3 gene are common in AML, including tandem repeats or a mutation in the kinase domain. (PMID:12854887)
- No significant correlation was found between FLT3 mutations and high levels of MDR1 in acute myeloid leukemia. (PMID:12926083)
- REVIEW: The role of FLT3 mutations in APL and other AML (PMID:12935959)
- wtFLT3 is often constitutively activated by FLT3 ligand in AML and thus, like its mutated form, might contribute to the altered signaling that characterizes leukemogenesis. (PMID:12969963)
- FLT3-D835/I836 mutations are one of the second genetic events in infant ALL with MLL rearrangements or pediatric ALL with hyperdiploidy (PMID:14504097)
- reduced AML1 activities predispose cells to the acquisition of the activating FLT3 mutation as a secondary event leading to full transformation in acute myeloblastic leukemia M0 (PMID:14562119)
- distinct activating FLT3-TKD mutations at position D835 mediate primary resistance to FLT3 PTK inhibitors in FLT3-transformed cell lines (PMID:14604974)
- FLT3 mutations are associated with molecular lesions in acute myeloid leukemias (PMID:14630076)
- Phosphorylation is inhibited by SU11248 in acute myeloid leukemia. (PMID:14654525)
- search for the presence of FLT3 mutations in leukemic blasts from 71 patients with childhood acute lymphoblastic leukemia discovered three novel in-frame deletions within a 7-amino acid region of the receptor juxtamembrane domain. (PMID:14670924)
- FLT3 analysis shows the autoinhibitory conformation of its complete juxtamembrane domain (PMID:14759363)
- FLT3 Asp(835) mutations may have a role in relapse of acute myeloid leukemia (PMID:14977832)
- FLT3 can negatively regulate Foxo transcription factors, thereby promoting cell survival and proliferation. (PMID:14981546)
- Mutations of Flt3 may disrupt transcriptional repressor function resulting in aberrant gene regulation and abnormal leukemia cell growth. (PMID:14982881)
- Activating mutations in the FLT3 RTK gene were found in each of 3 CD117/KIT(+) cases that were analyzed, but not in 52 other adult T-acute lymphoblastic leukemia (PMID:15044257)
- CXCR-4 expression was significantly higher in fetal liver tyrosine kinase-3 (Flt3)/internal tandem duplication (ITD) acute myeloid leukemia (PMID:15054042)
- Internal tandem duplication of the juxtamembrane domain or by activating point mutations in the second tyrosine kinase domain in FLT3 are associated with leukocytosis and the monocytic FAB subtypes M4 and M5. (PMID:15059064)
- Flt3 mutations identify patients at high risk of relapse (PMID:15061200)
- FLT3/internal tandem duplication(ITD) mutations confer a particularly poor prognosis in pediatric acute myelogenous leukemia patients (PMID:15166029)
- high frequency of FLT3 mutations in adult acute myelocytic leukemia without recurrent cytogenetic translocations. (PMID:15167911)
- FLT3 autoinhibited structure showed that N841 is the key residue in a hydrogen-bonding network that likely stabilizes the activation loop (PMID:15178581)
- Wild-type Flt3-overexpressing CD34+ cells exposed to high levels of its physiologic ligand did not produce early cobblestone areas (PMID:15242879)
- FLT3 has roles in different signal transduction pathways that control proliferation, survival and other processes in hematopoietic cells [review] (PMID:15253381)
- The loss of a clone with a mutation in the FLT3 gene at relapse did not improve the prognosis. (PMID:15289019)
- Inspection of the FLT3 structure revealed that Y842 is the key residue in regulating the switch from the closed to the open (= active) conformation of the FLT3 activation loop (PMID:15345593)
- mutations of specific residues located in the activation loop (D835X and 836-deletion in Flt-3; D816V in c-Kit) as well as a 6-base pair (6-bp) insertion at residue 840 in Flt-3 operate in a similar way (PMID:15363457)
- transformation of TF-1 cells with FLT3/ITD mutations suppressed the activity of SHP-1 by approximately 3-fold (PMID:15574429)
Cross-species orthologs
2 orthologs
| Organism | Symbol | Gene ID |
|---|---|---|
| mus_musculus | Flt3 | ENSMUSG00000042817 |
| rattus_norvegicus | Flt3 | ENSRNOG00000054764 |
Paralogs (53): INSRR (ENSG00000027644), MUSK (ENSG00000030304), FLT4 (ENSG00000037280), EPHA3 (ENSG00000044524), ROS1 (ENSG00000047936), LTK (ENSG00000062524), ERBB3 (ENSG00000065361), TIE1 (ENSG00000066056), FGFR2 (ENSG00000066468), FGFR3 (ENSG00000068078), EPHA8 (ENSG00000070886), FGFR1 (ENSG00000077782), EPHA6 (ENSG00000080224), TYRO3 (ENSG00000092445), FLT1 (ENSG00000102755), MET (ENSG00000105976), EPHB6 (ENSG00000106123), PDGFRB (ENSG00000113721), EPHA4 (ENSG00000116106), TEK (ENSG00000120156), KDR (ENSG00000128052), EPHB2 (ENSG00000133216), PDGFRA (ENSG00000134853), EPHA7 (ENSG00000135333), IGF1R (ENSG00000140443), NTRK3 (ENSG00000140538), ERBB2 (ENSG00000141736), EPHA2 (ENSG00000142627), EPHA5 (ENSG00000145242), EGFR (ENSG00000146648), EPHA1 (ENSG00000146904), NTRK2 (ENSG00000148053), MERTK (ENSG00000153208), EPHB1 (ENSG00000154928), KIT (ENSG00000157404), FGFR4 (ENSG00000160867), DDR2 (ENSG00000162733), RYK (ENSG00000163785), MST1R (ENSG00000164078), LMTK2 (ENSG00000164715), RET (ENSG00000165731), AXL (ENSG00000167601), ROR2 (ENSG00000169071), ALK (ENSG00000171094), INSR (ENSG00000171105), ERBB4 (ENSG00000178568), CSF1R (ENSG00000182578), EPHB3 (ENSG00000182580), EPHA10 (ENSG00000183317), ROR1 (ENSG00000185483), EPHB4 (ENSG00000196411), NTRK1 (ENSG00000198400), DDR1 (ENSG00000204580)
Mouse-model phenotypes
Observed phenotypes of the mouse ortholog (MGI:95559) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 79 distinct phenotype terms.
| Mouse phenotype (MP) | Records |
|---|---|
| increased leukocyte cell number | 3 |
| enlarged spleen | 3 |
| abnormal definitive hematopoiesis | 3 |
| abnormal B cell differentiation | 3 |
| increased monocyte cell number | 2 |
| extramedullary hematopoiesis | 2 |
| increased bone marrow cell number | 2 |
| increased granulocyte number | 2 |
| abnormal spleen morphology | 2 |
| arrested B cell differentiation | 2 |
| premature death | 2 |
| decreased B cell number | 2 |
| decreased NK cell number | 2 |
| increased pro-B cell number | 2 |
| decreased pre-B cell number | 2 |
| intermingled spleen red and white pulp | 2 |
| increased spleen white pulp amount | 2 |
| abnormal bone marrow cell number | 1 |
| increased neutrophil cell number | 1 |
| decreased leukocyte cell number | 1 |
| decreased neutrophil cell number | 1 |
| abnormal heart morphology | 1 |
| enlarged heart | 1 |
| decreased bone marrow cell number | 1 |
| abnormal skeletal muscle morphology | 1 |
+54 more (showing top 25).
Additional cross-species homologs
Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.
| Organism | UniProt | Identity | Method |
|---|---|---|---|
| Bos taurus | P43481 | 99.4% | Diamond |
| Capra hircus | Q28317 | 99.4% | Diamond |
| Felis catus | Q28889 | 99.2% | Diamond |
| Canis lupus familiaris | O97799 | 98.4% | Diamond |
| Sus scrofa | Q2HWD6 | 98.1% | Diamond |
| Callithrix jacchus | Q76II0 | 94.6% | Diamond |
| Gallus gallus | P18461 | 92.7% | Diamond |
| Notophthalmus viridescens | Q91147 | 87.9% | Diamond |
| Pleurodeles waltl | Q91285 | 87.8% | Diamond |
| Danio rerio | O73791 | 81.5% | Diamond |
| Coturnix coturnix | Q90330 | 81.0% | Diamond |
| Xenopus laevis | P22182 | 80.6% | Diamond |
| Takifugu rubripes | Q8AXC7 | 73.2% | Diamond |
| Coturnix japonica | P52583 | 73.1% | Diamond |
| Ciona intestinalis | Q4H3K6 | 60.1% | Diamond |
| Halocynthia roretzi | Q95YM9 | 59.9% | Diamond |
| Drosophila melanogaster | Q09147 | 55.0% | Diamond |
| Dugesia japonica | Q8MY86 | 51.0% | Diamond |
| Hydra vulgaris | Q86PM4 | 50.2% | Diamond |
| Caenorhabditis elegans | Q21038 | 49.5% | Diamond |
| Strongylocentrotus purpuratus | Q26614 | 46.4% | Diamond |
| Bombyx mori | D2IYS2 | 44.0% | Diamond |
| Feline sarcoma virus (STRAIN HARDY-ZUCKERMAN 4) | P04048 | 99.2% | Diamond |
| Feline sarcoma virus (STRAIN MCDONOUGH) | P00545 | 99.1% | Diamond |
Genomic neighbors (locus context)
Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).
| Symbol | Type | Entrez |
|---|---|---|
| PAN3 | protein-coding | 255967 |
| PAN3-AS1 | ncRNA | 100288730 |
| URAD | protein-coding | 646625 |
| LINC00543 | ncRNA | 100132234 |
| CDX2 | protein-coding | 1045 |
| FLT1 | protein-coding | 2321 |
Protein
Protein identifiers
Receptor-type tyrosine-protein kinase FLT3 — P36888 (reviewed: P36888)
Alternative names: FL cytokine receptor, Fetal liver kinase-2, Fms-like tyrosine kinase 3, Stem cell tyrosine kinase 1
All UniProt accessions (2): E7ER61, P36888
UniProt curated annotations — full annotation on UniProt →
Function. Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells. Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. Promotes activation of RAS signaling and phosphorylation of downstream kinases, including MAPK1/ERK2 and/or MAPK3/ERK1. Promotes phosphorylation of FES, FER, PTPN6/SHP, PTPN11/SHP-2, PLCG1, and STAT5A and/or STAT5B. Activation of wild-type FLT3 causes only marginal activation of STAT5A or STAT5B. Mutations that cause constitutive kinase activity promote cell proliferation and resistance to apoptosis via the activation of multiple signaling pathways.
Subunit / interactions. Monomer in the absence of bound FLT3LG. Homodimer in the presence of bound FLT3LG. Interacts with FIZ1 following ligand activation. Interacts with FES, FER, LYN, FGR, HCK, SRC and GRB2. Interacts with PTPRJ/DEP-1 and PTPN11/SHP2. Interacts with RNF115 and RNF126. (Microbial infection) Interacts with human cytomegalovirus protein UL7.
Subcellular location. Membrane. Endoplasmic reticulum lumen.
Tissue specificity. Detected in bone marrow, in hematopoietic stem cells, in myeloid progenitor cells and in granulocyte/macrophage progenitor cells (at protein level). Detected in bone marrow, liver, thymus, spleen and lymph node, and at low levels in kidney and pancreas. Highly expressed in T-cell leukemia.
Post-translational modifications. N-glycosylated, contains complex N-glycans with sialic acid. Autophosphorylated on several tyrosine residues in response to FLT3LG binding. FLT3LG binding also increases phosphorylation of mutant kinases that are constitutively activated. Dephosphorylated by PTPRJ/DEP-1, PTPN1, PTPN6/SHP-1, and to a lesser degree by PTPN12. Dephosphorylation is important for export from the endoplasmic reticulum and location at the cell membrane. Rapidly ubiquitinated by UBE2L6 and the E3 ubiquitin-protein ligase SIAH1 after autophosphorylation, leading to its proteasomal degradation.
Disease relevance. Leukemia, acute myelogenous (AML) [MIM:601626] A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes. The gene represented in this entry may be involved in disease pathogenesis. Somatic mutations that lead to constitutive activation of FLT3 are frequent in AML patients. These mutations fall into two classes, the most common being in-frame internal tandem duplications of variable length in the juxtamembrane region that disrupt the normal regulation of the kinase activity. Likewise, point mutations in the activation loop of the kinase domain can result in a constitutively activated kinase.
Activity regulation. Present in an inactive conformation in the absence of bound ligand. FLT3LG binding leads to dimerization and activation by autophosphorylation.
Domain organisation. The juxtamembrane autoregulatory region is important for normal regulation of the kinase activity and for maintaining the kinase in an inactive state in the absence of bound ligand. Upon tyrosine phosphorylation, it mediates interaction with the SH2 domains of numerous signaling partners. In-frame internal tandem duplications (ITDs) result in constitutive activation of the kinase. The activity of the mutant kinase can be stimulated further by FLT3LG binding.
Miscellaneous. Can be used as diagnostic tool to establish the exact cause of acute myeloid leukemia, and to determine the optimal therapy.
Similarity. Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.
Isoforms (2)
| UniProt ID | Names | Canonical? |
|---|---|---|
| P36888-1 | 1 | yes |
| P36888-2 | 2 |
RefSeq proteins (1): NP_004110* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR000719 | Prot_kinase_dom | Domain |
| IPR001245 | Ser-Thr/Tyr_kinase_cat_dom | Domain |
| IPR001824 | Tyr_kinase_rcpt_3_CS | Conserved_site |
| IPR007110 | Ig-like_dom | Domain |
| IPR008266 | Tyr_kinase_AS | Active_site |
| IPR011009 | Kinase-like_dom_sf | Homologous_superfamily |
| IPR013151 | Immunoglobulin_dom | Domain |
| IPR013783 | Ig-like_fold | Homologous_superfamily |
| IPR017441 | Protein_kinase_ATP_BS | Binding_site |
| IPR020635 | Tyr_kinase_cat_dom | Domain |
| IPR036179 | Ig-like_dom_sf | Homologous_superfamily |
| IPR050122 | RTK | Family |
Pfam: PF00047, PF07714
Enzyme classification (BRENDA)
- EC 2.7.10.1 — receptor protein-tyrosine kinase (BRENDA: 44 organisms, 214 substrates, 574 inhibitors, 11 Km, 0 kcat entries)
Substrate kinetics (BRENDA)
4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.
| Substrate | Km (mM) | Measurements |
|---|---|---|
| ATP | 0.0011–0.129 | 4 |
| AC-DYFE-6-CHLORO-W-NHME | 0.0051 | 1 |
| AC-DYFGW-NHME | 0.07 | 1 |
| YFEW | 0.232 | 1 |
Catalyzed reactions (Rhea)
- L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)
UniProt features (103 total): helix 18, strand 16, sequence variant 14, modified residue 13, glycosylation site 10, disulfide bond 7, sequence conflict 6, mutagenesis site 4, turn 3, binding site 2, topological domain 2, domain 2, signal peptide 1, chain 1, transmembrane region 1, splice variant 1, region of interest 1, active site 1
Structure
Experimental structures (PDB)
11 structures by resolution:
| PDB | Title | Method | Resolution (Å) |
|---|---|---|---|
| 1RJB | Crystal Structure of FLT3 | X-RAY DIFFRACTION | 2.1 |
| 6JQR | Crystal structure of FLT3 in complex with gilteritinib | X-RAY DIFFRACTION | 2.2 |
| 5X02 | Crystal structure of the FLT3 kinase domain bound to the inhibitor FF-10101 | X-RAY DIFFRACTION | 2.4 |
| 6IL3 | Crystal structure of the FLT3 kinase bound to a small molecule inhibitor | X-RAY DIFFRACTION | 2.5 |
| 8XB1 | Crystal structure of FLT3 in complex with a Pyrazinamide Macrocycle derivative | X-RAY DIFFRACTION | 2.85 |
| 4RT7 | Crystal Structure of FLT3 with a small molecule inhibitor | X-RAY DIFFRACTION | 3.1 |
| 4XUF | Crystal structure of the FLT3 kinase domain bound to the inhibitor quizartinib (AC220) | X-RAY DIFFRACTION | 3.2 |
| 7QDP | Crystal structure of FLT3 T343I in complex with the canonical ligand FL | X-RAY DIFFRACTION | 3.69 |
| 3QS7 | Crystal structure of a human Flt3 ligand-receptor ternary complex | X-RAY DIFFRACTION | 4.3 |
| 7ZV9 | Crystal structure of FLT3 in complex with a monomeric FLT3 Ligand variant | X-RAY DIFFRACTION | 4.51 |
| 3QS9 | Crystal structure of a human Flt3 ligand-receptor ternary complex | X-RAY DIFFRACTION | 7.8 |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-P36888-F1 | 76.19 | 0.30 |
Human Protein Atlas
Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, Tyr protein kinases, CD markers, Predicted membrane proteins, RAS pathway related proteins, Cancer-related genes, Mutated cancer genes, Mutational cancer driver genes, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes
Protein evidence: Evidence at protein level
Subcellular location (HPA, imaging): endoplasmic reticulum
Antibody reliability (HPA): IF approved
Functional residue map
Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.
Catalytic / active sites (1)
| Position | Role |
|---|---|
| 811 | proton acceptor |
Ligand- & substrate-binding residues (2)
| Position | Role |
|---|---|
| 644 | ATP |
| 616–624 | ATP |
Post-translational modifications (13)
| Type | Positions |
|---|---|
| Phosphotyrosine | 572, 589, 591, 599, 726, 768, 793, 842, 955, 969 |
| Phosphoserine | 574, 759, 993 |
Disulfide bonds (7)
| Type | Positions |
|---|---|
| Disulfide bond | 35–65, 103–114, 199–206, 232–241, 272–330, 368–407, 381–392 |
Glycosylation sites (10)
| Type | Positions |
|---|---|
| N-linked (glcnac…) asparagine | 43, 100, 151, 306, 323, 351, 354, 473, 502, 541 |
Mutagenesis-validated functional residues (4)
| Position | Phenotype |
|---|---|
| 589 | reduced phosphorylation of the wild-type kinase in response to ligand binding. no effect on the phosphorylation of the constitutively … |
| 591 | no significant effect on tyrosine phosphorylation. abolishes activation of stat5a. |
| 599 | abolishes interaction with ptpn11/shp2 and phosphorylation of ptpn11/shp2. |
| 644 | abolishes kinase activity. |
Function
Pathways and Gene Ontology
Reactome pathways
23 curated (TAS) of 46; 24 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).
46 pathways:
| ID | Pathway | Evidence |
|---|---|---|
| R-HSA-2219530 | Constitutive Signaling by Aberrant PI3K in Cancer ⚕ | curated |
| R-HSA-9702509 | FLT3 mutants bind TKIs ⚕ | curated |
| R-HSA-9706377 | FLT3 signaling by CBL mutants ⚕ | curated |
| R-HSA-9702569 | KW2449-resistant FLT3 mutants ⚕ | curated |
| R-HSA-9702518 | STAT5 activation downstream of FLT3 ITD mutants ⚕ | curated |
| R-HSA-9702581 | crenolanib-resistant FLT3 mutants ⚕ | curated |
| R-HSA-9702590 | gilteritinib-resistant FLT3 mutants ⚕ | curated |
| R-HSA-9702596 | lestaurtinib-resistant FLT3 mutants ⚕ | curated |
| R-HSA-9702998 | linifanib-resistant FLT3 mutants ⚕ | curated |
| R-HSA-9702600 | midostaurin-resistant FLT3 mutants ⚕ | curated |
| R-HSA-9702605 | pexidartinib-resistant FLT3 mutants ⚕ | curated |
| R-HSA-9702614 | ponatinib-resistant FLT3 mutants ⚕ | curated |
| R-HSA-9702620 | quizartinib-resistant FLT3 mutants ⚕ | curated |
| R-HSA-9702577 | semaxanib-resistant FLT3 mutants ⚕ | curated |
| R-HSA-9702624 | sorafenib-resistant FLT3 mutants ⚕ | curated |
| R-HSA-9702632 | sunitinib-resistant FLT3 mutants ⚕ | curated |
| R-HSA-9703009 | tamatinib-resistant FLT3 mutants ⚕ | curated |
| R-HSA-9702636 | tandutinib-resistant FLT3 mutants ⚕ | curated |
| R-HSA-9706369 | Negative regulation of FLT3 | curated |
| R-HSA-109704 | PI3K Cascade | curated |
| R-HSA-6811558 | PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling | curated |
| R-HSA-1257604 | PIP3 activates AKT signaling | curated |
| R-HSA-5673001 | RAF/MAP kinase cascade | curated |
| R-HSA-1643685 | Disease ⚕ | — |
| R-HSA-5663202 | Diseases of signal transduction by growth factor receptors and second messengers ⚕ | — |
| R-HSA-9702506 | Drug resistance of FLT3 mutants ⚕ | — |
| R-HSA-9682385 | FLT3 signaling in disease ⚕ | — |
| R-HSA-2219528 | PI3K/AKT Signaling in Cancer ⚕ | — |
| R-HSA-9703648 | Signaling by FLT3 ITD and TKD mutants ⚕ | electronic |
| R-HSA-1280215 | Cytokine Signaling in Immune system | — |
| R-HSA-9607240 | FLT3 Signaling | electronic |
| R-HSA-9706374 | FLT3 signaling through SRC family kinases | electronic |
| R-HSA-2428924 | IGF1R signaling cascade | — |
| R-HSA-112399 | IRS-mediated signalling | — |
| R-HSA-2428928 | IRS-related events triggered by IGF1R | — |
| R-HSA-168256 | Immune System | — |
| R-HSA-74751 | Insulin receptor signalling cascade | — |
| R-HSA-9006925 | Intracellular signaling by second messengers | — |
| R-HSA-5683057 | MAPK family signaling cascades | — |
| R-HSA-5684996 | MAPK1/MAPK3 signaling | — |
| R-HSA-199418 | Negative regulation of the PI3K/AKT network | — |
| R-HSA-9645135 | STAT5 Activation | electronic |
| R-HSA-162582 | Signal Transduction | — |
| R-HSA-74752 | Signaling by Insulin receptor | — |
| R-HSA-9006934 | Signaling by Receptor Tyrosine Kinases | — |
| R-HSA-2404192 | Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) | — |
MSigDB gene sets: 0 (showing top):
GO Biological Process (26): leukocyte homeostasis (GO:0001776), myeloid progenitor cell differentiation (GO:0002318), pro-B cell differentiation (GO:0002328), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), positive regulation of cell population proliferation (GO:0008284), cell migration (GO:0016477), peptidyl-tyrosine phosphorylation (GO:0018108), cytokine-mediated signaling pathway (GO:0019221), hemopoiesis (GO:0030097), B cell differentiation (GO:0030183), common myeloid progenitor cell proliferation (GO:0035726), positive regulation of tyrosine phosphorylation of STAT protein (GO:0042531), regulation of apoptotic process (GO:0042981), positive regulation of MAP kinase activity (GO:0043406), positive regulation of MAPK cascade (GO:0043410), lymphocyte proliferation (GO:0046651), protein autophosphorylation (GO:0046777), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), cellular response to cytokine stimulus (GO:0071345), cellular response to glucocorticoid stimulus (GO:0071385), dendritic cell differentiation (GO:0097028), liver regeneration (GO:0097421), protein phosphorylation (GO:0006468), cell surface receptor signaling pathway (GO:0007166), positive regulation of macromolecule metabolic process (GO:0010604), vascular endothelial growth factor signaling pathway (GO:0038084)
GO Molecular Function (15): protein tyrosine kinase activity (GO:0004713), transmembrane receptor protein tyrosine kinase activity (GO:0004714), cytokine receptor activity (GO:0004896), vascular endothelial growth factor receptor activity (GO:0005021), ATP binding (GO:0005524), growth factor binding (GO:0019838), nuclear glucocorticoid receptor binding (GO:0035259), protein-containing complex binding (GO:0044877), phosphatidylinositol 3-kinase activator activity (GO:0141038), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), transmembrane signaling receptor activity (GO:0004888), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)
GO Cellular Component (6): endoplasmic reticulum lumen (GO:0005788), plasma membrane (GO:0005886), endosome membrane (GO:0010008), signaling receptor complex (GO:0043235), membrane (GO:0016020), protein-containing complex (GO:0032991)
Reactome top-level categories
10 top-level categories:
| Category | Pathways |
|---|---|
| Drug resistance of FLT3 mutants | 11 |
| IRS-mediated signalling | 1 |
| Intracellular signaling by second messengers | 1 |
| PI3K/AKT Signaling in Cancer | 1 |
| MAPK1/MAPK3 signaling | 1 |
| Negative regulation of the PI3K/AKT network | 1 |
| Cytokine Signaling in Immune system | 1 |
| FLT3 Signaling | 1 |
| FLT3 signaling in disease | 1 |
| Signaling by FLT3 ITD and TKD mutants | 1 |
GO top-level categories
showing 60 of 69 GO namespaces:
| Category | Terms |
|---|---|
| cell population proliferation | 2 |
| protein phosphorylation | 2 |
| positive regulation of intracellular signal transduction | 2 |
| binding | 2 |
| immune system process | 1 |
| homeostasis of number of cells | 1 |
| hematopoietic progenitor cell differentiation | 1 |
| lymphoid progenitor cell differentiation | 1 |
| enzyme-linked receptor protein signaling pathway | 1 |
| regulation of cell population proliferation | 1 |
| positive regulation of cellular process | 1 |
| cell motility | 1 |
| cell surface receptor signaling pathway | 1 |
| cellular response to cytokine stimulus | 1 |
| cell development | 1 |
| lymphocyte differentiation | 1 |
| B cell activation | 1 |
| tyrosine phosphorylation of STAT protein | 1 |
| regulation of tyrosine phosphorylation of STAT protein | 1 |
| positive regulation of peptidyl-tyrosine phosphorylation | 1 |
| apoptotic process | 1 |
| regulation of programmed cell death | 1 |
| MAP kinase activity | 1 |
| regulation of MAP kinase activity | 1 |
| positive regulation of MAPK cascade | 1 |
| positive regulation of protein serine/threonine kinase activity | 1 |
| MAPK cascade | 1 |
| regulation of MAPK cascade | 1 |
| mononuclear cell proliferation | 1 |
| lymphocyte activation | 1 |
| phosphatidylinositol 3-kinase/protein kinase B signal transduction | 1 |
| regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | 1 |
| response to cytokine | 1 |
| response to glucocorticoid | 1 |
| cellular response to corticosteroid stimulus | 1 |
| protein kinase activity | 1 |
| protein tyrosine kinase activity | 1 |
| transmembrane receptor protein kinase activity | 1 |
| transmembrane signaling receptor activity | 1 |
| cytokine-mediated signaling pathway | 1 |
| cytokine binding | 1 |
| immune receptor activity | 1 |
| transmembrane receptor protein tyrosine kinase activity | 1 |
| vascular endothelial growth factor signaling pathway | 1 |
| vascular endothelial growth factor binding | 1 |
| adenyl ribonucleotide binding | 1 |
| purine ribonucleoside triphosphate binding | 1 |
| anion binding | 1 |
| protein binding | 1 |
| nuclear receptor binding | 1 |
| phosphatidylinositol 3-kinase regulator activity | 1 |
| nucleoside phosphate binding | 1 |
| heterocyclic compound binding | 1 |
| kinase activity | 1 |
| phosphotransferase activity, alcohol group as acceptor | 1 |
| catalytic activity, acting on a protein | 1 |
| signaling receptor activity | 1 |
| transferase activity, transferring phosphorus-containing groups | 1 |
| catalytic activity | 1 |
| endoplasmic reticulum | 1 |
Experimentally-supported GO annotations
GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 47 annotations. The rest are phylogenetic / computational / electronic (IEA).
1 experimentally-supported GO terms:
| GO term | NS | Evidence |
|---|---|---|
| hemopoiesis | BP | direct assay |
Protein interactions and networks
STRING
showing 15 of 2,904 interactions by confidence (×1000):
| Protein A | Protein B | Partner UniProt | Score |
|---|---|---|---|
| FLT3 | NPM1 | P06748 | 930 |
| FLT3 | CD34 | P28906 | 865 |
| FLT3 | FLT3LG | P49771 | 863 |
| FLT3 | ASXL1 | Q8IXJ9 | 862 |
| FLT3 | DNMT3A | Q9Y6K1 | 844 |
| FLT3 | TET2 | Q6N021 | 840 |
| FLT3 | IL7R | P16871 | 822 |
| FLT3 | SLAMF1 | Q13291 | 820 |
| FLT3 | IDH1 | O75874 | 800 |
| FLT3 | CEBPA | P49715 | 800 |
| FLT3 | RUNX1 | Q01196 | 800 |
| FLT3 | IL3 | P08700 | 798 |
| FLT3 | KITLG | P21583 | 792 |
| FLT3 | IDH2 | P48735 | 792 |
| FLT3 | PHF6 | Q8IWS0 | 780 |
IntAct
Human interaction partners of FLT3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).
22 partners by confidence:
| Partner | Interaction type | MIscore | Records |
|---|---|---|---|
| SYK | direct interaction | 0.740 | 22 |
| GRB10 | physical association | 0.590 | 6 |
| ABL2 | direct interaction | 0.540 | 3 |
| PTPN11 | association | 0.460 | 2 |
| ABL1 | direct interaction | 0.440 | 2 |
| CRK | direct interaction | 0.440 | 2 |
| CRKL | direct interaction | 0.440 | 2 |
| FYN | direct interaction | 0.440 | 2 |
| LCK | direct interaction | 0.440 | 2 |
| RASA1 | direct interaction | 0.440 | 2 |
| BLK | direct interaction | 0.440 | 1 |
| FLT3LG | direct interaction | 0.440 | 1 |
| SOCS6 | direct interaction | 0.440 | 1 |
| TNS1 | direct interaction | 0.440 | 1 |
| YES1 | direct interaction | 0.440 | 1 |
| PIK3R1 | physical association | 0.400 | 2 |
| MRPS28 | physical association | 0.400 | 1 |
| CLGN | association | 0.350 | 1 |
| LANCL1 | association | 0.350 | 1 |
| PTPRJ | proximity | 0.270 | 3 |
| KIF2A | proximity | 0.270 | 1 |
| IKBKG | direct interaction | 0.000 | 2 |
BioGRID (330 interactions; top human partners by supporting records): CBL (Affinity Capture-Western; 3 records), CTNNB1 (Affinity Capture-Western; 3 records), PTPN11 (Reconstituted Complex; 3 records), SLA (Affinity Capture-Western; 3 records), CALM3 (Affinity Capture-MS; 2 records), HSPA1B (Affinity Capture-MS; 2 records), PIK3R1 (Affinity Capture-Western; 2 records), PPAN (Positive Genetic; 2 records), SIAH1 (Reconstituted Complex; 2 records), SOCS1 (Affinity Capture-MS; 2 records), SOCS2 (Affinity Capture-Western; 2 records), UBE2L6 (Affinity Capture-Western; 2 records), ABCG5 (Positive Genetic), ADCK3 (Proximity Label-MS), AFG3L2 (Proximity Label-MS)
SIGNOR signaling
showing 50 of 115 signaling interactions:
| A | Effect | B | Mechanism |
|---|---|---|---|
| FLT3 | up-regulates | FLT3 | phosphorylation |
| sunitinib | down-regulates | FLT3 | “chemical inhibition” |
| anthra[1,9-cd]pyrazol-6(2H)-one | down-regulates | FLT3 | “chemical inhibition” |
| CHIR-124 | down-regulates | FLT3 | “chemical inhibition” |
| 4-amino-5-fluoro-3-[5-(4-methyl-1-piperazinyl)-1,3-dihydrobenzimidazol-2-ylidene]-2-quinolinone | down-regulates | FLT3 | “chemical inhibition” |
| “dovitinib; bis(lactic acid)” | down-regulates | FLT3 | “chemical inhibition” |
| [4-[2-(1H-indazol-3-yl)ethenyl]phenyl]-(1-piperazinyl)methanone | down-regulates | FLT3 | “chemical inhibition” |
| MK-2461 | down-regulates | FLT3 | “chemical inhibition” |
| FLT3 | up-regulates | Skeletal_muscle_differentiation | |
| quizartinib | down-regulates | FLT3 | “chemical inhibition” |
| tandutinib | down-regulates | FLT3 | “chemical inhibition” |
| TG101209 | down-regulates | FLT3 | “chemical inhibition” |
| FLT3 | “up-regulates activity” | AKT | |
| FLT3 | “down-regulates quantity by repression” | CEBPA | “transcriptional regulation” |
| FLT3 | “up-regulates activity” | SHC1 | phosphorylation |
| FLT3 | “up-regulates activity” | AKT1 | |
| FLT3 | “up-regulates activity” | RUNX1 | |
| sunitinib | “down-regulates activity” | FLT3 | “chemical inhibition” |
| regorafenib | “down-regulates activity” | FLT3 | “chemical inhibition” |
| PIM1 | “up-regulates quantity” | FLT3 | phosphorylation |
| FLT3 | “down-regulates quantity” | PTPN6 | “transcriptional regulation” |
| FLT3 | “up-regulates activity” | Glycolysis | |
| FLT3 | “up-regulates activity” | CTNNB1 | phosphorylation |
| FLT3 | “up-regulates activity” | ERK1/2 | |
| FLT3 | “up-regulates activity” | HK2 | |
| FLT3 | “down-regulates quantity by repression” | PTPN6 | “transcriptional regulation” |
| FLT3 | “up-regulates quantity by stabilization” | SIRT1 | “post transcriptional regulation” |
| FLT3 | “up-regulates quantity by expression” | MYC | |
| FLT3 | “up-regulates quantity by expression” | USP22 | “transcriptional regulation” |
| cabozantinib | “down-regulates activity” | FLT3 | “chemical inhibition” |
| FLT3 | “up-regulates activity” | ACAT1 | phosphorylation |
| FLT3 | “down-regulates activity” | IDH2 | phosphorylation |
| FLT3 | “up-regulates activity” | Hexokinase | |
| FLT3 | “up-regulates activity” | FLT3 | phosphorylation |
| PTPRJ | “down-regulates activity” | FLT3 | dephosphorylation |
| SYK | “up-regulates activity” | FLT3 | phosphorylation |
| FYN | “up-regulates activity” | FLT3 | phosphorylation |
| FLT3LG | up-regulates | FLT3 | binding |
| FLT3 | “up-regulates activity” | PTPN11 | binding |
| FLT3 | “up-regulates activity” | GRB2 | binding |
| FLT3 | “up-regulates activity” | STAT5A | phosphorylation |
| FLT3 | “up-regulates quantity by expression” | ID1 | “transcriptional regulation” |
| CBL | “down-regulates activity” | FLT3 | binding |
| FLT3 | “up-regulates quantity by expression” | miR-155 | “transcriptional regulation” |
| FLT3 | “up-regulates activity” | GRB10 | binding |
| SLA2 | “down-regulates activity” | FLT3 | binding |
| FLT3 | “up-regulates activity” | PIK3R1 | |
| FLT3 | “up-regulates activity” | PI3K | |
| CBLB | “down-regulates activity” | FLT3 | ubiquitination |
| FLT3 | “up-regulates quantity by expression” | FZD4 | “transcriptional regulation” |
Protein complexes (CORUM) (5)
Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).
5 complexes by size:
| Complex | Subunits | Members |
|---|---|---|
| ★ FLT3-FLT3LG complex | 2 | FLT3LG, FLT3 |
| ★ FLT3-SET complex | 2 | FLT3, SET |
| ★ CDKN1B-FLT3 complex | 2 | CDKN1B, FLT3 |
| ★ FES-FLT3 complex | 2 | FES, FLT3 |
| ★ FER-FLT3 complex | 2 | FER, FLT3 |
Ligand–receptor pairs (CellPhoneDB) (1)
Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.
1 ligand–receptor pairs:
| Partner | This gene’s role | Signaling class |
|---|---|---|
| FLT3LG | receptor |
Enriched among interaction partners
Reactome pathways and GO biological processes over-represented among this gene’s 22 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.
Reactome pathways:
| Pathway | Partners | Fold | FDR |
|---|---|---|---|
| Regulation of signaling by CBL | 6 | 156.8× | 1e-10 |
| FLT3 Signaling | 8 | 145.7× | 5e-14 |
| Downstream signal transduction | 5 | 100.2× | 7e-08 |
| Signaling by SCF-KIT | 7 | 91.5× | 9e-11 |
| GPVI-mediated activation cascade | 5 | 81.2× | 2e-07 |
| FCGR3A-mediated phagocytosis | 5 | 49.3× | 1e-06 |
| Constitutive Signaling by Aberrant PI3K in Cancer | 5 | 33.4× | 6e-06 |
| PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling | 5 | 25.5× | 2e-05 |
GO biological processes:
| GO term | Partners | Fold | FDR |
|---|---|---|---|
| ephrin receptor signaling pathway | 6 | 93.8× | 1e-08 |
| cellular response to transforming growth factor beta stimulus | 5 | 62.8× | 2e-06 |
| T cell receptor signaling pathway | 6 | 41.4× | 1e-06 |
| intracellular signal transduction | 8 | 13.9× | 4e-06 |
Disease & clinical
Cancer significance
From CIViC — curated cancer-variant interpretation:
FLT3 is an important cytokine receptor involved in normal hematopoiesis. Mutations in this gene are common in acute myeloid leukemia (AML) and screening for mutations in this gene has been recommended by the World Health Organization in patients with AML, particularly in cases of cytogenetically normal AML (CN-AML). FLT3 mutations commonly co-occur with mutations such as NPM1 that are associated with CN-AML and likely modulate prognostic impact. While FLT3-ITD mutations have been associated with poorer prognosis in AML, the prognostic impact of FLT3-TKD mutations are still up for debate.
From intOGen — cancer-driver classification: activating (oncogene-like) across 2 cancer types — ALL, AML.
intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.
Genetic variants
Variant evidence for FLT3: 247 ClinVar records (14 pathogenic / likely pathogenic); 20 CIViC cancer variants; 1 PharmGKB clinical annotation; 63 GWAS associations. Per-variant detail is on Sugi Variant.
ClinVar
247 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 10 |
| Likely pathogenic | 4 |
| Uncertain significance | 80 |
| Likely benign | 40 |
| Benign | 85 |
Top pathogenic / likely-pathogenic (14)
Showing all 14 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.
| Variant ID | HGVS | Classification | Review | Submitters |
|---|---|---|---|---|
| 219096 | NM_004119.3(FLT3):c.1773_1793dup (p.Tyr597_Glu598insAspValAspPheArgGluTyr) | Pathogenic | criteria provided, single submitter | 1 |
| 2572500 | NM_004119.3(FLT3):c.2533A>G (p.Arg845Gly) | Likely pathogenic | criteria provided, single submitter | 1 |
| 4528371 | NM_004119.3(FLT3):c.1715A>G (p.Tyr572Cys) | Likely pathogenic | criteria provided, single submitter | 1 |
| 16276 | NM_004119.3(FLT3):c.2503G>T (p.Asp835Tyr) | Pathogenic | no assertion criteria provided | 3 |
| 16272 | NM_004119.3(FLT3):c.2504A>T (p.Asp835Val) | Pathogenic | no assertion criteria provided | 2 |
| 16270 | FLT3, INTERNAL TANDEM DUP | Pathogenic | no assertion criteria provided | 1 |
| 16271 | NM_004119.3(FLT3):c.2520_2521insGGATCC (p.Ser840_Asn841insGlySer) | Pathogenic | no assertion criteria provided | 1 |
| 16273 | NM_004119.3(FLT3):c.2503G>C (p.Asp835His) | Pathogenic | no assertion criteria provided | 1 |
| 16274 | NM_004119.3(FLT3):c.2503G>A (p.Asp835Asn) | Pathogenic | no assertion criteria provided | 1 |
| 16277 | NM_004119.3(FLT3):c.2503_2505del (p.Asp835del) | Pathogenic | no assertion criteria provided | 1 |
| 16278 | NM_004119.3(FLT3):c.1777_1779del (p.Asp593del) | Pathogenic | no assertion criteria provided | 1 |
| 375972 | NM_004119.3(FLT3):c.2505T>A (p.Asp835Glu) | Pathogenic | no assertion criteria provided | 1 |
| 590265 | t(13;17)(q12.2;q11.2) | Likely pathogenic | no assertion criteria provided | 1 |
| 800354 | NM_004119.3(FLT3):c.1714T>C (p.Tyr572His) | Likely pathogenic | no assertion criteria provided | 1 |
Per-variant reference — Sugi Variant
Explore FLT3’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.
SpliceAI
Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 32 predictions of 2,456):
| Position(s) | Effect | Δscore | Sites |
|---|---|---|---|
| 13:28015588–28015589 | donor_loss | 1.0000 | 5 |
| 13:28015702–28015703 | acceptor_loss | 1.0000 | 5 |
| 13:28015714–28015715 | acceptor_gain | 1.0000 | 2 |
| 13:28023374 | donor_gain | 1.0000 | |
| 13:28028176–28028177 | donor_loss | 1.0000 | 5 |
| 13:28034080–28034081 | donor_loss | 1.0000 | 5 |
| 13:28034085 | donor_gain | 1.0000 | |
| 13:28037293 | acceptor_gain | 1.0000 | |
| 13:28062070–28062071 | acceptor_loss | 1.0000 | 2 |
| 13:28070489–28070490 | donor_loss | 1.0000 | 5 |
AlphaMissense
1,717 missense substitutions predicted likely pathogenic (of 6,557 scored), across 404 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:
| Residue | Likely-pathogenic substitutions | Mean am_pathogenicity | Max am_pathogenicity |
|---|---|---|---|
| M908 | 9 | 0.954 | 0.997 |
| M855 | 9 | 0.951 | 0.995 |
| M799 | 9 | 0.931 | 0.995 |
| M645 | 9 | 0.858 | 0.957 |
| M922 | 9 | 0.853 | 0.994 |
| N816 | 8 | 0.998 | 0.999 |
| D829 | 8 | 0.998 | 1.000 |
| D811 | 8 | 0.997 | 1.000 |
| H809 | 8 | 0.994 | 0.998 |
| D870 | 8 | 0.994 | 0.998 |
| F621 | 8 | 0.989 | 1.000 |
| F830 | 8 | 0.985 | 0.998 |
| D698 | 8 | 0.978 | 0.996 |
| F882 | 8 | 0.975 | 0.998 |
| F936 | 8 | 0.974 | 0.997 |
| F898 | 8 | 0.970 | 0.998 |
| D787 | 8 | 0.962 | 0.989 |
| F605 | 8 | 0.956 | 0.999 |
| S869 | 8 | 0.955 | 1.000 |
| D835 | 8 | 0.934 | 0.975 |
HPA cancer prognostics
RNA cancer specificity: Cancer enhanced (Breast Invasive Carcinoma)
Disease associations
OMIM: gene MIM:136351 | disease phenotypes: MIM:601626, MIM:254500
GenCC curated gene-disease
1 curated gene-disease records:
| Disease | Classification | Inheritance | Records |
|---|---|---|---|
| leukemia, acute myeloid, susceptibility to | Limited | Autosomal dominant |
ClinGen Gene-Disease Validity
Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.
1 validity classifications:
| Disease | Classification | Inheritance |
|---|---|---|
| leukemia, acute myeloid, susceptibility to | Limited | AD |
Genomics England panels (PanelApp)
Clinical diagnostic gene panels including this gene (1 panels, 0 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.
1 panels:
| Panel | Rating |
|---|---|
| Cytopenias and congenital anaemias | amber |
Mondo (5): acute myeloid leukemia (MONDO:0018874), acute lymphoblastic leukemia (MONDO:0004967), atypical chronic myeloid leukemia, BCR-ABL1 negative (MONDO:0004653), plasma cell myeloma (MONDO:0009693), leukemia, acute myeloid, susceptibility to (MONDO:0100173)
Orphanet (5): Acute myeloid leukemia (Orphanet:519), Acute lymphoblastic leukemia (Orphanet:513), Atypical chronic myeloid leukemia (Orphanet:98824), Multiple myeloma (Orphanet:29073), AL amyloidosis (Orphanet:85443)
HPO phenotypes
5 phenotypes (HPO-id order):
| HPO | Term |
|---|---|
| HP:0000006 | Autosomal dominant inheritance |
| HP:0001442 | Typified by somatic mosaicism |
| HP:0004808 | Acute myeloid leukemia |
| HP:0006721 | Acute lymphoblastic leukemia |
| HP:0010982 | Polygenic inheritance |
GWAS associations
showing 30 of 63 associations:
| Study | Trait | p-value |
|---|---|---|
| GCST90002393_231 | Monocyte count | 0.000000e+00 |
| GCST90002394_159 | Monocyte percentage of white cells | 0.000000e+00 |
| GCST004625_31 | Monocyte count | 3e-240 |
| GCST004609_180 | Monocyte percentage of white cells | 4e-188 |
| GCST004608_125 | Granulocyte percentage of myeloid white cells | 2e-136 |
| GCST90002393_236 | Monocyte count | 4e-117 |
| GCST90002394_160 | Monocyte percentage of white cells | 1e-109 |
| GCST90002393_232 | Monocyte count | 5e-92 |
| GCST90002407_445 | White blood cell count | 4e-83 |
| GCST90002394_164 | Monocyte percentage of white cells | 4e-68 |
| GCST004625_32 | Monocyte count | 2e-41 |
| GCST90002393_234 | Monocyte count | 2e-40 |
| GCST90002407_446 | White blood cell count | 9e-40 |
| GCST90002398_346 | Neutrophil count | 3e-38 |
| GCST90002398_347 | Neutrophil count | 9e-35 |
| GCST90002389_423 | Lymphocyte percentage of white cells | 2e-33 |
| GCST007932_49 | Medication use (thyroid preparations) | 2e-26 |
| GCST90002393_233 | Monocyte count | 3e-25 |
| GCST004609_179 | Monocyte percentage of white cells | 5e-25 |
| GCST010571_59 | Autoimmune thyroid disease | 2e-24 |
| GCST90002407_447 | White blood cell count | 1e-23 |
| GCST010989_154 | Body size at age 10 | 1e-22 |
| GCST90002389_422 | Lymphocyte percentage of white cells | 2e-22 |
| GCST004626_61 | Myeloid white cell count | 8e-21 |
| GCST004610_79 | White blood cell count | 2e-19 |
| GCST90002394_161 | Monocyte percentage of white cells | 4e-19 |
| GCST90002394_163 | Monocyte percentage of white cells | 8e-19 |
| GCST008129_11 | Body mass index | 1e-18 |
| GCST90002393_235 | Monocyte count | 1e-18 |
| GCST90002394_162 | Monocyte percentage of white cells | 4e-18 |
EFO canonical traits (from GWAS)
18 canonical traits:
| EFO ID | Trait name |
|---|---|
| EFO:0004340 | body mass index |
| EFO:0005091 | monocyte count |
| EFO:0007997 | granulocyte percentage of myeloid white cells |
| EFO:0007989 | monocyte percentage of leukocytes |
| EFO:0004833 | neutrophil count |
| EFO:0004842 | eosinophil count |
| EFO:0007987 | granulocyte count |
| EFO:0005090 | basophil count |
| EFO:0007993 | lymphocyte percentage of leukocytes |
| EFO:0005301 | reading and spelling ability |
| EFO:0009933 | Thyroid preparation use measurement |
| EFO:0004614 | apolipoprotein A 1 measurement |
| EFO:0004612 | high density lipoprotein cholesterol measurement |
| EFO:0009819 | comparative body size at age 10, self-reported |
| EFO:0004587 | lymphocyte count |
| EFO:0010701 | mean reticulocyte volume |
| EFO:0007990 | neutrophil percentage of leukocytes |
| EFO:0007985 | platelet crit |
MeSH disease descriptors
2 disease descriptors:
| Descriptor | Name | Tree numbers |
|---|---|---|
| D015470 | Leukemia, Myeloid, Acute | C04.557.337.539.275; C15.378.508.539.275 |
| D009101 | Multiple Myeloma | C04.557.595.500; C14.907.454.460; C15.378.147.780.650; C15.378.463.515.460; C20.683.515.845; C20.683.780.650 |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (4): CHEMBL1974 (SINGLE PROTEIN), CHEMBL3430908 (SELECTIVITY GROUP), CHEMBL4523735 (PROTEIN-PROTEIN INTERACTION), CHEMBL4630730 (PROTEIN-PROTEIN INTERACTION)
Drugs by curated mechanism of action (ChEMBL)
Drugs whose curated ChEMBL mechanism of action targets the FLT3 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.
39 curated-mechanism drugs:
| Drug | Modality | Max phase |
|---|---|---|
| FEDRATINIB | Small molecule | 4 |
| GILTERITINIB | Small molecule | 4 |
| MIDOSTAURIN | Small molecule | 4 |
| PACRITINIB | Small molecule | 4 |
| PEXIDARTINIB | Small molecule | 4 |
| QUIZARTINIB | Small molecule | 4 |
| SORAFENIB TOSYLATE | Small molecule | 4 |
| SUNITINIB | Small molecule | 4 |
| CM-082 | Unknown | 3 |
| CRENOLANIB | Small molecule | 3 |
| DOVITINIB | Small molecule | 3 |
| FAMITINIB | Small molecule | 3 |
| LESTAURTINIB | Small molecule | 3 |
| LINIFANIB | Small molecule | 3 |
| RUSERONTINIB | Small molecule | 3 |
| AKN-028 | Small molecule | 2 |
| AMUVATINIB | Small molecule | 2 |
| AT-9283 | Small molecule | 2 |
| C-1311 | Small molecule | 2 |
| CDX-301 | Unknown | 2 |
| ENMD-2076 | Small molecule | 2 |
| ENMD-981693 | Small molecule | 2 |
| FORETINIB | Small molecule | 2 |
| NINGETINIB | Small molecule | 2 |
| SU-014813 | Small molecule | 2 |
| TANDUTINIB | Small molecule | 2 |
| XL-999 | Small molecule | 2 |
| ZOTIRACICLIB | Small molecule | 2 |
| 4SC-203 | Small molecule | 1 |
| AMG553 | Unknown | 1 |
| AS-602868 | Small molecule | 1 |
| AST-487 | Small molecule | 1 |
| CEP-2563 DIHYDROCHLORIDE | Small molecule | 1 |
| CT-1578 | Small molecule | 1 |
| FF-10101 | Small molecule | 1 |
| FLYSYN | Unknown | 1 |
| IMC-EB10 | Unknown | 1 |
| KW-2449 | Small molecule | 1 |
| RG-1530 | Small molecule | 1 |
Molecules with ChEMBL bioactivity
Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 402,854 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).
showing 60 of 143 molecules by phase:
| Molecule | Name | Phase | Patents |
|---|---|---|---|
| CHEMBL1287853 | FEDRATINIB | 4 | 3,770 |
| CHEMBL3301622 | GILTERITINIB | 4 | 2,542 |
| CHEMBL608533 | MIDOSTAURIN | 4 | 7,641 |
| CHEMBL2035187 | PACRITINIB | 4 | 3,544 |
| CHEMBL3813873 | PEXIDARTINIB | 4 | 3,751 |
| CHEMBL576982 | QUIZARTINIB | 4 | 4,647 |
| CHEMBL2105709 | QUIZARTINIB DIHYDROCHLORIDE | 4 | 304 |
| CHEMBL1336 | SORAFENIB | 4 | 87,476 |
| CHEMBL535 | SUNITINIB | 4 | 80,232 |
| CHEMBL3301610 | ABEMACICLIB | 4 | 7,497 |
| CHEMBL1173655 | AFATINIB | 4 | 15,878 |
| CHEMBL1289926 | AXITINIB | 4 | 16,510 |
| CHEMBL288441 | BOSUTINIB | 4 | 12,869 |
| CHEMBL3545311 | BRIGATINIB | 4 | 5,988 |
| CHEMBL2105717 | CABOZANTINIB | 4 | 11,799 |
| CHEMBL2403108 | CERITINIB | 4 | 9,002 |
| CHEMBL601719 | CRIZOTINIB | 4 | 15,133 |
| CHEMBL5416410 | DASATINIB | 4 | 674 |
| CHEMBL1983268 | ENTRECTINIB | 4 | 3,737 |
| CHEMBL553 | ERLOTINIB | 4 | 109,860 |
| CHEMBL3301607 | FILGOTINIB | 4 | |
| CHEMBL2103830 | FOSTAMATINIB | 4 | |
| CHEMBL939 | GEFITINIB | 4 | |
| CHEMBL1873475 | IBRUTINIB | 4 | |
| CHEMBL941 | IMATINIB | 4 | |
| CHEMBL1852688 | INFIGRATINIB | 4 | |
| CHEMBL1834657 | INFIGRATINIB PHOSPHATE | 4 | |
| CHEMBL180022 | NERATINIB | 4 | |
| CHEMBL255863 | NILOTINIB | 4 | |
| CHEMBL502835 | NINTEDANIB | 4 | |
| CHEMBL189963 | PALBOCICLIB | 4 | |
| CHEMBL477772 | PAZOPANIB | 4 | |
| CHEMBL1171837 | PONATINIB | 4 | |
| CHEMBL4582651 | PRALSETINIB | 4 | |
| CHEMBL1946170 | REGORAFENIB | 4 | |
| CHEMBL1289494 | TIVOZANIB | 4 | |
| CHEMBL24828 | VANDETANIB | 4 | |
| CHEMBL2105728 | CRENOLANIB | 3 | |
| CHEMBL522892 | DOVITINIB | 3 | |
| CHEMBL603469 | LESTAURTINIB | 3 | |
| CHEMBL223360 | LINIFANIB | 3 | |
| CHEMBL428690 | ALVOCIDIB | 3 | |
| CHEMBL415049 | BARASERTIB | 3 | |
| CHEMBL31965 | CANERTINIB | 3 | |
| CHEMBL491473 | CEDIRANIB | 3 | |
| CHEMBL3137331 | DEFACTINIB | 3 | |
| CHEMBL3265032 | ENTOSPLETINIB | 3 | |
| CHEMBL300138 | ENZASTAURIN | 3 | |
| CHEMBL3904602 | LEROCICLIB | 3 | |
| CHEMBL1091644 | LINSITINIB | 3 | |
| CHEMBL572881 | MOTESANIB | 3 | |
| CHEMBL2316582 | OLVEREMBATINIB | 3 | |
| CHEMBL274654 | ORANTINIB | 3 | |
| CHEMBL50 | QUERCETIN | 3 | |
| CHEMBL165 | RESVERATROL | 3 | |
| CHEMBL91829 | RUBOXISTAURIN | 3 | |
| CHEMBL217092 | SARACATINIB | 3 | |
| CHEMBL276711 | SEMAXANIB | 3 | |
| CHEMBL3989926 | SITRAVATINIB | 3 | |
| CHEMBL4297190 | SURUFATINIB | 3 |
Clinical evidence (CIViC)
Drug × variant × indication, from 99 curated evidence items; also 25 prognostic, 10 oncogenic, 5 diagnostic, 1 functional. CIViC evidence level: A (validated) → B (clinical) → C (case study) → D (preclinical) → E (inferential).
showing 30 of 81 predictive associations by evidence level:
| Variant | Therapy | Indication | Effect | Level | CIViC |
|---|---|---|---|---|---|
| FLT3 ITD | Gilteritinib | Acute Myeloid Leukemia | Sensitivity/Response | CIViC A | EID12621 +2 |
| FLT3 ITD OR FLT3 D835 OR FLT3 I836 | Midostaurin + Chemotherapy | Acute Myeloid Leukemia | Sensitivity/Response | CIViC A | EID11261 |
| FLT3 ITD OR FLT3 D835 OR FLT3 I836 | Gilteritinib | Acute Myeloid Leukemia | Sensitivity/Response | CIViC A | EID7728 |
| FLT3 Mutation | Midostaurin | Acute Myeloid Leukemia | Sensitivity/Response | CIViC A | EID5261 |
| FLT3 ITD | Sorafenib | Acute Myeloid Leukemia | Sensitivity/Response | CIViC B | EID1040 +2 |
| FLT3 F691L | Pexidartinib | Acute Myeloid Leukemia | Sensitivity/Response | CIViC B | EID8674 +1 |
| FLT3 ITD | Midostaurin | Acute Myeloid Leukemia | Sensitivity/Response | CIViC B | EID7061 +1 |
| FLT3 Mutation | Nilotinib | Acute Myeloid Leukemia | Sensitivity/Response | CIViC B | EID5575 +1 |
| FLT3 Amplification | Sunitinib | Colorectal Cancer | Sensitivity/Response | CIViC B | EID11667 |
| FLT3 ITD | Lestaurtinib | Acute Myeloid Leukemia | Sensitivity/Response | CIViC B | EID297 |
| FLT3 ITD | Hematopoietic Cell Transplantation + Sorafenib | Acute Myeloid Leukemia | Sensitivity/Response | CIViC B | EID9069 |
| FLT3 ITD | Sorafenib + Hematopoietic Cell Transplantation | Acute Myeloid Leukemia | Sensitivity/Response | CIViC B | EID9070 |
| FLT3 ITD | Pacritinib | Acute Myeloid Leukemia | Sensitivity/Response | CIViC B | EID9217 |
| FLT3 Mutation | Gilteritinib | Acute Myeloid Leukemia | Sensitivity/Response | CIViC B | EID7283 |
| FLT3 TKD MUTATION | Midostaurin | Acute Myeloid Leukemia | Sensitivity/Response | CIViC B | EID1295 |
| FLT3 F691L | Quizartinib | Acute Myeloid Leukemia | Resistance | CIViC B | EID9718 +1 |
| FLT3 D835 | Quizartinib + Sorafenib | Acute Myeloid Leukemia | Resistance | CIViC B | EID1038 |
| FLT3 D835 | Sorafenib | Acute Myeloid Leukemia | Resistance | CIViC B | EID1039 |
| FLT3 F691L | Pexidartinib | Acute Myeloid Leukemia | Resistance | CIViC B | EID9717 |
| FLT3 ITD | Anthracycline Antineoplastic Antibiotic + Tretinoin | Acute Promyelocytic Leukemia | Resistance | CIViC B | EID1112 |
| FLT3 ITD | Selumetinib | Acute Myeloid Leukemia | Resistance | CIViC B | EID1137 |
| FLT3 ITD | Tretinoin | Acute Myeloid Leukemia | Resistance | CIViC B | EID127 |
| FLT3 TKD MUTATION | Sorafenib | Acute Myeloid Leukemia | Resistance | CIViC B | EID248 |
| FLT3 T227M | Sunitinib | Renal Cell Carcinoma | Adverse Response | CIViC B | EID1317 |
| FLT3 D835 | Sunitinib | Acute Myeloid Leukemia | Sensitivity/Response | CIViC C | EID4024 +2 |
| FLT3 D835V | Sunitinib | Acute Myeloid Leukemia | Sensitivity/Response | CIViC C | EID4022 +2 |
| FLT3 D835Y | Sorafenib | Acute Myeloid Leukemia | Sensitivity/Response | CIViC C | EID12625 +2 |
| FLT3 D835H | Sunitinib | Acute Myeloid Leukemia | Sensitivity/Response | CIViC C | EID4027 +1 |
| FLT3 D835Y | Gilteritinib | Acute Myeloid Leukemia | Sensitivity/Response | CIViC C | EID12620 +1 |
| FLT3 Amplification | Regorafenib Anhydrous | Colorectal Cancer | Sensitivity/Response | CIViC C | EID7102 |
CIViC column: a representative evidence item (EID); +N = additional CIViC items supporting the same association.
Clinical-actionability assertions (CIViC AMP/ASCO/CAP)
Curated AMP/ASCO/CAP tier assertions — the clinical-actionability classification (Tier I highest) for this gene’s variants, distilling the CIViC evidence above into a tiered call.
5 CIViC assertions:
| Molecular profile | Disease | Therapy | Type | AMP tier | Significance |
|---|---|---|---|---|---|
| FLT3 D835Y | Acute Myeloid Leukemia | Gilteritinib † | Predictive | Tier I - Level A | Sensitivity/Response |
| FLT3 D835 | Acute Myeloid Leukemia | Gilteritinib † | Predictive | Tier I - Level A | Sensitivity/Response |
| FLT3 ITD | Acute Myeloid Leukemia | Gilteritinib † | Predictive | Tier I - Level A | Sensitivity/Response |
| FLT3 N841I | Acute Myeloid Leukemia | Oncogenic | Oncogenic | ||
| FLT3 D835Y | Acute Myeloid Leukemia | Oncogenic | Oncogenic |
† an FDA-approved companion diagnostic exists for this assertion.
CIViC curated variants (20)
Named clinical variants curated in CIViC for this gene (the catalogue beneath the predictive evidence above):
D835V (missense variant), Amplification, D835Y (missense variant), Y842C, F691L, D835I, N841I (missense variant), I836, I836S, I836T, D593del, D835 (protein altering variant), Mutation (gain of function variant,transcript variant), T227M (missense variant,SNP), M737I, ITD (inframe insertion), TKD MUTATION, Overexpression, D835H (missense variant), D835H/Y (missense variant).
PharmGKB: 1 entry (CPIC guideline: no)
PharmGKB clinical annotations
1 annotations by evidence level (1 strongest → 4):
| Variant | Association | Level | Drugs | Phenotypes |
|---|---|---|---|---|
| rs1933437 | Toxicity | 3 | sunitinib | Leukopenia;Myelosuppression;Neutropenia;Thrombocytopenia |
PharmGKB variants
1 variants:
| Variant | Genes | Level | Score | #Clin annots | Drugs |
|---|---|---|---|---|---|
| rs1933437 | FLT3 | 3 | 6.50 | 1 | sunitinib |
PharmGKB variant annotations
Per-publication pharmacogenomic findings for this gene (significant associations).
3 published findings:
| Variant | Drug(s) | Category | Finding | PMID |
|---|---|---|---|---|
| rs1933437 | sunitinib | Toxicity | Genotype AA is associated with increased risk of Leukopenia and Neutropenia when treated with sunitinib in people with Carcinoma, Renal Cell as compared to genotypes AG + GG. | PMID:26244574 |
| rs1933437 | sunitinib | Toxicity | Genotypes AG + GG is associated with decreased likelihood of Leukopenia when treated with sunitinib in people with Carcinoma, Renal Cell or Gastrointestinal Stromal Tumors as compared to genotype AA. | PMID:19667267 |
| rs1933437 | sunitinib | Toxicity | Genotypes AG + GG is associated with decreased likelihood of Thrombocytopenia when treated with sunitinib in people with Carcinoma, Renal Cell or Gastrointestinal Stromal Tumors as compared to genotype AA. | PMID:20683446 |
GtoPdb / IUPHAR curated pharmacology
(IUPHAR/BPS Guide to Pharmacology — expert-curated)
Target class: catalytic receptor — Type III RTKs: PDGFR, CSFR, Kit, FLT3 receptor family
Most potent curated ligand interactions (68 total), top 25:
| Ligand | Action | Affinity | Parameter |
|---|---|---|---|
| faldoritinib | Irreversible inhibition | 10.0 | pIC50 |
| gilteritinib | Inhibition | 9.52 | pIC50 |
| nefextinib | Inhibition | 9.47 | pIC50 |
| denfivontinib | Inhibition | 9.4 | pIC50 |
| AC710 | Inhibition | 9.3 | pKd |
| Gö 6976 | Inhibition | 9.15 | pIC50 |
| TTT-3002 | Inhibition | 9.14 | pIC50 |
| crenolanib | Inhibition | 9.13 | pKd |
| compound 8i [PMID: 22765894] | Inhibition | 9.1 | pIC50 |
| compound 8h [PMID: 22765894] | Inhibition | 9.07 | pIC50 |
| dorsomorphin | Inhibition | 9.0 | pIC50 |
| dovitinib | Inhibition | 9.0 | pIC50 |
| RGB-286638 | Inhibition | 9.0 | pIC50 |
| ilorasertib | Inhibition | 9.0 | pIC50 |
| tuspetinib | Inhibition | 8.96 | pIC50 |
| compound 2c [PMID: 24900538] | Inhibition | 8.68 | pIC50 |
| compound 6li [Chan et al., 2022] | Inhibition | 8.6 | pKd |
| ENMD-2076 | Inhibition | 8.52 | pIC50 |
| compound 5e [PMID: 28580438] | Inhibition | 8.44 | pKd |
| faronoltinib | Inhibition | 8.4 | pIC50 |
| compound 34f [PMID: 37535845] | Inhibition | 8.4 | pIC50 |
| linifanib | Inhibition | 8.4 | pIC50 |
| URMC-099 | Inhibition | 8.4 | pIC50 |
| quizartinib | Inhibition | 8.38 | pIC50 |
| mivavotinib | Inhibition | 8.34 | pIC50 |
Binding affinities (BindingDB)
3824 measured of 4881 human assays (4965 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.
| Ligand | Measure | Value | Patent |
|---|---|---|---|
| [6-cyclopropyl-3-[6-[[(3S,4S)-4-fluoropyrrolidin-3-yl]amino]-2-pyridinyl]imidazo[1,2-a]pyridin-7-yl]methanol | KD | 0.007 nM | US-20230303563: MULTI-CYCLIC IRAK AND FLT3 INHIBITING COMPOUNDS AND USES THEREOF |
| 6-[6-(difluoromethyl)imidazo[1,2-a]pyridin-3-yl]-N-[(3S,4S)-4-fluoropyrrolidin-3-yl]pyridin-2-amine | KD | 0.007 nM | US-20230303563: MULTI-CYCLIC IRAK AND FLT3 INHIBITING COMPOUNDS AND USES THEREOF |
| Exemplary Synthetic Procedure #38 | KD | 0.008 nM | US-20230303563: MULTI-CYCLIC IRAK AND FLT3 INHIBITING COMPOUNDS AND USES THEREOF |
| 2-(3-(6-(((3S,4S)-4- fluoropyrrolidin-3- yl)amino)pyridin-2-yl)-7- methoxyimidazo[1,2- a]pyridin-6-yl)propan-2-ol | KD | 0.009 nM | US-20230303563: MULTI-CYCLIC IRAK AND FLT3 INHIBITING COMPOUNDS AND USES THEREOF |
| 6-(6- (difluoromethyl)imidazo[1,2- a]pyridin-3-yl)-N-((3R,4S)-4- (trifluoromethyl)pyrrolidin-3- yl)pyridin-2-amine | KD | 0.009 nM | US-20230303563: MULTI-CYCLIC IRAK AND FLT3 INHIBITING COMPOUNDS AND USES THEREOF |
| 6-(6- (difluoromethyl)imidazo[1,2- a]pyridin-3-yl)-N-(2,2- dimethylpyrrolidin-3- yl)pyridin-2-amine | KD | 0.009 nM | US-20230303563: MULTI-CYCLIC IRAK AND FLT3 INHIBITING COMPOUNDS AND USES THEREOF |
| N-(6-(6- (difluoromethyl)imidazo[1,2- a]pyridin-3-yl)pyridin-2-yl)-2- azaspiro[3.4]octan-6-amine | KD | 0.01 nM | US-20230303563: MULTI-CYCLIC IRAK AND FLT3 INHIBITING COMPOUNDS AND USES THEREOF |
| 6-(6-(difluorometh- oxy)imidazo[1,2-a]- pyridin-3-yl)-N-((3S, 4S)-4-fluoropyrrolidin- 3-yl)pyridin-2-amine | KD | 0.011 nM | US-20230303563: MULTI-CYCLIC IRAK AND FLT3 INHIBITING COMPOUNDS AND USES THEREOF |
| 6-(6-(1-cyclopropyl-1H- pyrazol-4-yl)imidazo- [1,2-a]pyridin-3-yl)-N- ((3S,4S)-4-fluoro- pyrrolidin-3-yl)pyridin- 2-amine | KD | 0.011 nM | US-20230303563: MULTI-CYCLIC IRAK AND FLT3 INHIBITING COMPOUNDS AND USES THEREOF |
| N-((3S,4S)-4-fluoro- pyrrolidin-3-yl)-6-(6-(1- methyl-1H-pyrazol-4- yl)imidazo[1,2-a]pyridin- 3-yl)pyridin-2-amine | KD | 0.012 nM | US-20230303563: MULTI-CYCLIC IRAK AND FLT3 INHIBITING COMPOUNDS AND USES THEREOF |
| CHEMBL4744130 | IC50 | 0.015 nM | |
| 1-(4-(3-(6-(((3S,4S)-4- fluoropyrrolidin-3-yl)- amino)pyridin-2-yl)- imidazo[1,2-a]pyridin-6- yl)-1H-pyrazol-1-yl)-2- methylpropan-2-ol | KD | 0.016 nM | US-20230303563: MULTI-CYCLIC IRAK AND FLT3 INHIBITING COMPOUNDS AND USES THEREOF |
| 2-(3-(6-(((3S,4S)-4- fluoropiperidin-3- yl)amino)pyridin-2-yl)-7- methoxyimidazo[1,2- a]pyridin-6-yl)propan-2-ol | KD | 0.017 nM | US-20230303563: MULTI-CYCLIC IRAK AND FLT3 INHIBITING COMPOUNDS AND USES THEREOF |
| N-((3S,4S)-4- fluoropyrrolidin-3-yl)-6-(7- isopropoxyimidazo[1,2- a]pyridin-3-yl)pyridin-2- amine | KD | 0.018 nM | US-20230303563: MULTI-CYCLIC IRAK AND FLT3 INHIBITING COMPOUNDS AND USES THEREOF |
| (R)-N-(6-(6- (difluoromethyl)imidazo[1,2- a]pyridin-3-yl)pyridin-2-yl)-5- azaspiro[2.4]heptan-7-amine | KD | 0.02 nM | US-20230303563: MULTI-CYCLIC IRAK AND FLT3 INHIBITING COMPOUNDS AND USES THEREOF |
| CHEMBL5440655 | IC50 | 0.024 nM | |
| 3,5-difluoro-N-((3S,4S)-4- fluoropiperidin-3-yl)-6-(7- isopropoxyimidazo[1,2- a]pyridin-3-yl)pyridin-2- amine | KD | 0.025 nM | US-20230303563: MULTI-CYCLIC IRAK AND FLT3 INHIBITING COMPOUNDS AND USES THEREOF |
| N-(6-(6-(1-methyl- cyclopropyl)imidazo- [1,2-a]pyridin-3-yl)- pyridin-2-yl)-2- azaspiro[3.4]octan-6- amine | KD | 0.034 nM | US-20230303563: MULTI-CYCLIC IRAK AND FLT3 INHIBITING COMPOUNDS AND USES THEREOF |
| CHEMBL4519741 | IC50 | 0.038 nM | |
| 3,5-difluoro-N-((3S,4S)-4- fluoropyrrolidin-3-yl)-6- (7- isopropoxyimidazo[1,2- a]pyridin-3-yl)pyridin-2- amine | KD | 0.049 nM | US-20230303563: MULTI-CYCLIC IRAK AND FLT3 INHIBITING COMPOUNDS AND USES THEREOF |
| 3-[2-(Imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide | EC50 | 0.05 nM | |
| CHEMBL6191359 | IC50 | 0.05 nM | |
| CHEMBL6191849 | IC50 | 0.05 nM | |
| CHEMBL6192901 | IC50 | 0.05 nM | |
| CHEMBL6189235 | IC50 | 0.05 nM | |
| (17E)-16-ethyl-8,12,14-trimethyl- 2,11,12,14-tetrahydro-8H-3,5- ethenotripyrazolo[3,4-f:3’,4’-j:4″,3″- n][1,4]oxazacyclopentadecin-13(10H)- one | KD | 0.058 nM | US-20260070924: INDAZOLE MACROCYCLES AND THEIR USE |
| CHEMBL6192930 | IC50 | 0.06 nM | |
| CHEMBL5641913 | IC50 | 0.061 nM | |
| CHEMBL5641673 | IC50 | 0.061 nM | |
| CHEMBL5639694 | IC50 | 0.063 nM | |
| CHEMBL5639591 | IC50 | 0.063 nM | |
| CHEMBL4790915 | IC50 | 0.072 nM | |
| CHEMBL6188781 | IC50 | 0.08 nM | |
| CHEMBL6189029 | IC50 | 0.08 nM | |
| CHEMBL6192679 | IC50 | 0.08 nM | |
| CHEMBL6191366 | IC50 | 0.09 nM | |
| CHEMBL5639373 | IC50 | 0.102 nM | |
| CHEMBL5593388 | IC50 | 0.11 nM | |
| CHEMBL5646935 | IC50 | 0.117 nM | |
| CHEMBL5647067 | IC50 | 0.118 nM | |
| CHEMBL5646820 | IC50 | 0.119 nM | |
| CHEMBL5639601 | IC50 | 0.132 nM | |
| CHEMBL6190161 | IC50 | 0.14 nM | |
| CHEMBL5618643 | IC50 | 0.142 nM | |
| CHEMBL5639222 | IC50 | 0.147 nM | |
| CHEMBL5639369 | IC50 | 0.147 nM | |
| CHEMBL4790597 | IC50 | 0.15 nM | |
| CHEMBL6189611 | IC50 | 0.15 nM | |
| CHEMBL6192249 | IC50 | 0.16 nM | |
| CHEMBL5640024 | IC50 | 0.168 nM |
ChEMBL bioactivities
6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
| pChembl | Type | Value | Unit | Molecule |
|---|---|---|---|---|
| 11.00 | Kd | 0.01 | nM | CHEMBL5176837 |
| 11.00 | Kd | 0.01 | nM | CHEMBL5927784 |
| 10.92 | Kd | 0.012 | nM | CHEMBL5176837 |
| 10.82 | IC50 | 0.015 | nM | CHEMBL4744130 |
| 10.81 | Kd | 0.0154 | nM | CHEMBL5195819 |
| 10.80 | Kd | 0.016 | nM | CRENOLANIB |
| 10.77 | Kd | 0.017 | nM | CHEMBL6078253 |
| 10.68 | Kd | 0.021 | nM | CHEMBL6002371 |
| 10.62 | IC50 | 0.024 | nM | CHEMBL5440655 |
| 10.60 | Kd | 0.025 | nM | CHEMBL5927784 |
| 10.47 | Kd | 0.034 | nM | CHEMBL6078253 |
| 10.42 | IC50 | 0.038 | nM | CHEMBL4519741 |
| 10.30 | IC50 | 0.05 | nM | CHEMBL6191359 |
| 10.30 | IC50 | 0.05 | nM | CHEMBL6191849 |
| 10.30 | IC50 | 0.05 | nM | CHEMBL6192901 |
| 10.30 | IC50 | 0.05 | nM | CHEMBL6189235 |
| 10.25 | Kd | 0.056 | nM | CHEMBL6078253 |
| 10.22 | IC50 | 0.06 | nM | CRENOLANIB |
| 10.22 | IC50 | 0.06 | nM | CHEMBL6192930 |
| 10.21 | IC50 | 0.061 | nM | CHEMBL5641913 |
| 10.21 | IC50 | 0.061 | nM | CHEMBL5641673 |
| 10.20 | IC50 | 0.063 | nM | CHEMBL5639694 |
| 10.20 | IC50 | 0.063 | nM | CHEMBL5639591 |
| 10.19 | Kd | 0.065 | nM | CHEMBL6002371 |
| 10.14 | IC50 | 0.072 | nM | CHEMBL4790915 |
| 10.13 | Kd | 0.074 | nM | CHEMBL6078253 |
| 10.10 | IC50 | 0.08 | nM | CHEMBL6188781 |
| 10.10 | IC50 | 0.08 | nM | CHEMBL6189029 |
| 10.10 | IC50 | 0.08 | nM | CHEMBL6192679 |
| 10.05 | IC50 | 0.09 | nM | CHEMBL6191366 |
| 10.03 | Kd | 0.093 | nM | CHEMBL256961 |
| 10.00 | IC50 | 0.101 | nM | CHEMBL4086149 |
| 10.00 | IC50 | 0.1 | nM | CHEMBL4513768 |
| 10.00 | Ki | 0.1 | nM | CHEMBL4864449 |
| 10.00 | Ki | 0.1 | nM | CHEMBL4870188 |
| 10.00 | IC50 | 0.1 | nM | CHEMBL5268237 |
| 10.00 | Kd | 0.1 | nM | CHEMBL6078253 |
| 10.00 | Ki | 0.1 | nM | CHEMBL273187 |
| 9.99 | IC50 | 0.102 | nM | CHEMBL5639373 |
| 9.96 | IC50 | 0.11 | nM | CHEMBL5593388 |
| 9.96 | Kd | 0.11 | nM | CHEMBL6002371 |
| 9.93 | IC50 | 0.118 | nM | CHEMBL5647067 |
| 9.93 | IC50 | 0.117 | nM | CHEMBL5646935 |
| 9.92 | IC50 | 0.121 | nM | CHEMBL5440655 |
| 9.92 | IC50 | 0.119 | nM | CHEMBL5646820 |
| 9.92 | Kd | 0.12 | nM | CHEMBL6002371 |
| 9.91 | IC50 | 0.123 | nM | CHEMBL3612622 |
| 9.89 | IC50 | 0.13 | nM | CHEMBL4092761 |
| 9.88 | IC50 | 0.132 | nM | CHEMBL5639601 |
| 9.85 | IC50 | 0.14 | nM | CHEMBL6190161 |
PubChem BioAssay actives
3025 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.
| Compound | Assay | Type | Value | Unit |
|---|---|---|---|---|
| 6-[7-methoxy-6-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]-N-pyrrolidin-3-ylpyridin-2-amine | 1894563: Binding affinity to FLT3-ITD-D835V mutant (unknown origin) assessed as dissociation constant | kd | <0.0001 | uM |
| 1-(5-tert-butyl-1,2-oxazol-3-yl)-3-[3-fluoro-4-(1H-imidazo[4,5-b]pyridin-7-yloxy)phenyl]urea | 1696916: Inhibition of FLT3 ITD mutant (unknown origin) expressed in mouse BaF3 cells | ic50 | <0.0001 | uM |
| 2-[3-[6-[[(3S,4S)-4-fluoropiperidin-3-yl]amino]-2-pyridinyl]-7-methoxyimidazo[1,2-a]pyridin-6-yl]propan-2-ol | 2205385: Binding affinity to FLT3 D835V mutant (unknown origin) expressed in Escherichia coli BL21 assessed as dissociation constant by DiscoverX KINOMEscan assay | kd | <0.0001 | uM |
| 6-(6-cyclopropyl-7-methoxyimidazo[1,2-a]pyridin-3-yl)-N-[(3S,4S)-4-fluoropyrrolidin-3-yl]pyridin-2-amine | 2205370: Inhibition of NanoLuc-fused FLT3 ITD/D835Y mutant (unknown origin) transfected in HEK293 cells incubated for 1 hr by NanoBRET assay | ic50 | <0.0001 | uM |
| 2-[(E)-[2-(2-hydroxy-1H-indol-3-yl)indol-3-ylidene]amino]oxy-1-piperazin-1-ylethanone;hydrochloride | 1868178: Binding affinity to FLT3 ITD/F691L double mutant (unknown origin) by KINOMEscan assay | kd | <0.0001 | uM |
| N-[(5-methyl-1H-imidazol-2-yl)methyl]-4-(8,9,10,11-tetrahydro-3H-pyrazolo[4,5-a]phenanthridin-7-yl)benzamide | 2003941: Inhibition of FLT3 D835Y mutant (unknown origin) | ic50 | <0.0001 | uM |
| 1-[2-[5-[(3-methyloxetan-3-yl)methoxy]benzimidazol-1-yl]quinolin-8-yl]piperidin-4-amine | 1562814: Inhibition of FLT3 D835Y mutant (unknown origin) | ic50 | 0.0001 | uM |
| 5-chloro-3-[1-(2-methyl-5-nitrophenyl)sulfonylpyrrol-3-yl]pyrazolo[1,5-a]pyrimidine | 1245695: Inhibition of FLT3 (unknown origin) using biotin-Glu-Gly-Pro-Trp-Leu-Glu-Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 as substrate after 90 mins by luminescence assay | ic50 | 0.0001 | uM |
| 1-(5-tert-butyl-1,2-oxazol-3-yl)-3-[4-(6,7-dimethoxyquinolin-4-yl)oxy-3-fluorophenyl]urea | 1696916: Inhibition of FLT3 ITD mutant (unknown origin) expressed in mouse BaF3 cells | ic50 | 0.0001 | uM |
| N-[6-(4-ethylpiperazin-1-yl)-2-methylpyrimidin-4-yl]-5-pyridin-4-yl-1,3-thiazol-2-amine;hydrochloride | 1581288: Inhibition of wild type FLT3 (unknown origin) expressed in HEK293T cells assessed as decrease in FLT3 phosphorylation at 0.1 to 1000 nM after 1 hr by Western blot analysis | ic50 | 0.0001 | uM |
| 4-[(6-ethylthieno[2,3-d]pyrimidin-4-yl)amino]-N-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]-1H-pyrazole-5-carboxamide | 1489804: Inhibition of human FLT3 using EAIYAAPFAKKK as substrate preincubated for 20 mins followed by [gamma-33P]-ATP addition measure after 120 mins by filter binding method | ic50 | 0.0001 | uM |
| N-[4-(diethylaminomethyl)phenyl]-4-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-1H-pyrazole-5-carboxamide | 1489804: Inhibition of human FLT3 using EAIYAAPFAKKK as substrate preincubated for 20 mins followed by [gamma-33P]-ATP addition measure after 120 mins by filter binding method | ic50 | 0.0001 | uM |
| 4-[3-[(E)-2-[3-fluoro-4-(morpholin-4-ylmethyl)phenyl]ethenyl]-1H-indazol-6-yl]pyrimidin-2-amine | 2279207: Inhibition of His-tagged human recombinant FLT3 catalytic domain (564 to 958 residues) expressed in insect cells using ATP as substrate incubated for 60 mins by LanthaScreen analysis | ic50 | 0.0001 | uM |
| 4-[3-[(E)-2-(4-morpholin-4-ylphenyl)ethenyl]-1H-indazol-6-yl]pyridin-2-amine | 2279207: Inhibition of His-tagged human recombinant FLT3 catalytic domain (564 to 958 residues) expressed in insect cells using ATP as substrate incubated for 60 mins by LanthaScreen analysis | ic50 | 0.0001 | uM |
| 4-[3-[(E)-2-[4-(4-methylpiperazin-1-yl)phenyl]ethenyl]-1H-indazol-6-yl]pyridin-2-amine | 2279207: Inhibition of His-tagged human recombinant FLT3 catalytic domain (564 to 958 residues) expressed in insect cells using ATP as substrate incubated for 60 mins by LanthaScreen analysis | ic50 | 0.0001 | uM |
| 4-[3-[(E)-2-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]ethenyl]-1H-indazol-6-yl]pyridin-2-amine | 2279207: Inhibition of His-tagged human recombinant FLT3 catalytic domain (564 to 958 residues) expressed in insect cells using ATP as substrate incubated for 60 mins by LanthaScreen analysis | ic50 | 0.0001 | uM |
| 4-[3-[(E)-2-[3-fluoro-4-(morpholin-4-ylmethyl)phenyl]ethenyl]-1H-indazol-6-yl]pyridin-2-amine | 2279207: Inhibition of His-tagged human recombinant FLT3 catalytic domain (564 to 958 residues) expressed in insect cells using ATP as substrate incubated for 60 mins by LanthaScreen analysis | ic50 | 0.0001 | uM |
| N-[(2S,4S,6R)-2,6-dimethyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]-N-methylbenzamide | 1691299: Inhibition of human FLT3 D835Y mutant EAIYAAPFAKKK peptide as substrate in presence of 33P-gamma ATP by hotspot kinase assay | ic50 | 0.0001 | uM |
| 1-[4-[3-[[4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-yl]amino]phenyl]-1,4-diazepan-1-yl]ethanone | 1756404: Inhibition of FLT3 ITD mutant (unknown origin) using Glu/Tyr peptide substrate incubated for 120 mins measured after 40 mins incubation under dark by ADP-glo based luminescence assay | ki | 0.0001 | uM |
| 1-[4-[4-[[4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyrimidin-2-yl]amino]phenyl]piperazin-1-yl]ethanone | 1756404: Inhibition of FLT3 ITD mutant (unknown origin) using Glu/Tyr peptide substrate incubated for 120 mins measured after 40 mins incubation under dark by ADP-glo based luminescence assay | ki | 0.0001 | uM |
| 3-(6-morpholin-4-yl-1H-benzimidazol-2-yl)-N-[(3R)-pyrrolidin-3-yl]-1H-indazole-5-carboxamide | 2143345: Inhibition of recombinant wild type FLT3 kinase domain (unknown origin) using peptide substrate incubated for for 30 mins by HTRF assay | ic50 | 0.0001 | uM |
| (4-aminopiperidin-1-yl)-[3-(6-morpholin-4-yl-1H-benzimidazol-2-yl)-1H-indazol-5-yl]methanone | 2143345: Inhibition of recombinant wild type FLT3 kinase domain (unknown origin) using peptide substrate incubated for for 30 mins by HTRF assay | ic50 | 0.0001 | uM |
| N-(3-aminopropyl)-3-(6-morpholin-4-yl-1H-benzimidazol-2-yl)-1H-indazole-5-carboxamide | 2143345: Inhibition of recombinant wild type FLT3 kinase domain (unknown origin) using peptide substrate incubated for for 30 mins by HTRF assay | ic50 | 0.0001 | uM |
| N-[(1S,3S)-3-aminocyclopentyl]-3-(6-morpholin-4-yl-1H-benzimidazol-2-yl)-1H-indazole-5-carboxamide | 2143345: Inhibition of recombinant wild type FLT3 kinase domain (unknown origin) using peptide substrate incubated for for 30 mins by HTRF assay | ic50 | 0.0001 | uM |
| N-(3-aminopropyl)-3-(6-piperidin-1-yl-1H-benzimidazol-2-yl)-1H-indazole-5-carboxamide | 2143345: Inhibition of recombinant wild type FLT3 kinase domain (unknown origin) using peptide substrate incubated for for 30 mins by HTRF assay | ic50 | 0.0001 | uM |
| N-[(1S,3R)-3-aminocyclopentyl]-3-(6-morpholin-4-yl-1H-benzimidazol-2-yl)-1H-indazole-5-carboxamide | 2143345: Inhibition of recombinant wild type FLT3 kinase domain (unknown origin) using peptide substrate incubated for for 30 mins by HTRF assay | ic50 | 0.0001 | uM |
| N-[(1S,3S)-3-aminocyclopentyl]-3-(6-methoxy-1H-benzimidazol-2-yl)-1H-indazole-5-carboxamide | 2143349: Inhibition of recombinant FLT3 D835Y mutant (unknown origin) using peptide substrate incubated for for 30 mins by HTRF assay | ic50 | 0.0001 | uM |
| 3-(6-morpholin-4-yl-1H-benzimidazol-2-yl)-N-[[(3S)-pyrrolidin-3-yl]methyl]-1H-indazole-5-carboxamide | 2143345: Inhibition of recombinant wild type FLT3 kinase domain (unknown origin) using peptide substrate incubated for for 30 mins by HTRF assay | ic50 | 0.0001 | uM |
| N-[3-(dimethylamino)propyl]-3-(6-morpholin-4-yl-1H-benzimidazol-2-yl)-1H-indazole-5-carboxamide | 2143345: Inhibition of recombinant wild type FLT3 kinase domain (unknown origin) using peptide substrate incubated for for 30 mins by HTRF assay | ic50 | 0.0001 | uM |
| 3-(6-morpholin-4-yl-1H-benzimidazol-2-yl)-N-[[(3R)-pyrrolidin-3-yl]methyl]-1H-indazole-5-carboxamide | 2143345: Inhibition of recombinant wild type FLT3 kinase domain (unknown origin) using peptide substrate incubated for for 30 mins by HTRF assay | ic50 | 0.0001 | uM |
| N-(4-aminocyclohexyl)-3-(6-morpholin-4-yl-1H-benzimidazol-2-yl)-1H-indazole-5-carboxamide | 2143345: Inhibition of recombinant wild type FLT3 kinase domain (unknown origin) using peptide substrate incubated for for 30 mins by HTRF assay | ic50 | 0.0001 | uM |
| piperazin-1-yl-[4-[(E)-2-(6-pyridin-4-yl-1H-indazol-3-yl)ethenyl]phenyl]methanone | 2279207: Inhibition of His-tagged human recombinant FLT3 catalytic domain (564 to 958 residues) expressed in insect cells using ATP as substrate incubated for 60 mins by LanthaScreen analysis | ic50 | 0.0001 | uM |
| [4-[(E)-2-[6-(2-amino-4-pyridinyl)-1H-indazol-3-yl]ethenyl]phenyl]-morpholin-4-ylmethanone | 2279207: Inhibition of His-tagged human recombinant FLT3 catalytic domain (564 to 958 residues) expressed in insect cells using ATP as substrate incubated for 60 mins by LanthaScreen analysis | ic50 | 0.0001 | uM |
| 3-N-[4-(4-morpholin-4-ylcyclohexyl)phenyl]-1-pyridin-2-yl-1,2,4-triazole-3,5-diamine | 649408: Inhibition of human recombinant FLT3 by radiometric assay | ki | 0.0002 | uM |
| N-[(E)-(5-cyanopyrazolo[1,5-a]pyrimidin-3-yl)methylideneamino]-N,2-dimethyl-5-nitrobenzenesulfonamide | 1245695: Inhibition of FLT3 (unknown origin) using biotin-Glu-Gly-Pro-Trp-Leu-Glu-Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 as substrate after 90 mins by luminescence assay | ic50 | 0.0002 | uM |
| N-[2-(5-chloropyrazolo[1,5-a]pyrimidin-3-yl)ethyl]-2-methyl-5-nitrobenzenesulfonamide | 1245695: Inhibition of FLT3 (unknown origin) using biotin-Glu-Gly-Pro-Trp-Leu-Glu-Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 as substrate after 90 mins by luminescence assay | ic50 | 0.0002 | uM |
| N-[2-(5-chloropyrazolo[1,5-a]pyrimidin-3-yl)ethyl]-5-cyano-N,2-dimethylbenzenesulfonamide | 1245695: Inhibition of FLT3 (unknown origin) using biotin-Glu-Gly-Pro-Trp-Leu-Glu-Glu-Glu-Glu-Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 as substrate after 90 mins by luminescence assay | ic50 | 0.0002 | uM |
| 4-[3-[(E)-2-[4-(morpholin-4-ylmethyl)phenyl]ethenyl]-1H-indazol-6-yl]pyridin-2-amine | 2279207: Inhibition of His-tagged human recombinant FLT3 catalytic domain (564 to 958 residues) expressed in insect cells using ATP as substrate incubated for 60 mins by LanthaScreen analysis | ic50 | 0.0002 | uM |
| 4-[(2-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-yl)amino]-N-(4-piperazin-1-ylphenyl)-1H-pyrazole-5-carboxamide | 1360758: Inhibition of human FLT3 by Hotspot assay | ic50 | 0.0002 | uM |
| 2-[4-(4-acetylpiperazin-1-yl)anilino]-4-(1H-indazol-3-yl)pyrimidine-5-carbonitrile | 1756404: Inhibition of FLT3 ITD mutant (unknown origin) using Glu/Tyr peptide substrate incubated for 120 mins measured after 40 mins incubation under dark by ADP-glo based luminescence assay | ki | 0.0002 | uM |
| 2-[(E)-[2-(2-hydroxy-1H-indol-3-yl)indol-3-ylidene]amino]oxy-N-[(3S)-pyrrolidin-3-yl]acetamide;hydrochloride | 1868174: Inhibition of human recombinant His-tagged FLT3/D835Y mutant expressed in baculovirus expression system incubated for 30 mins in presence of ATP by HTRF analysis | ic50 | 0.0002 | uM |
| 2-[(E)-[2-(5-chloro-2-hydroxy-1H-indol-3-yl)indol-3-ylidene]amino]oxy-1-piperazin-1-ylethanone;hydrochloride | 1868174: Inhibition of human recombinant His-tagged FLT3/D835Y mutant expressed in baculovirus expression system incubated for 30 mins in presence of ATP by HTRF analysis | ic50 | 0.0002 | uM |
| 2-[(E)-[2-(2-hydroxy-1H-indol-3-yl)indol-3-ylidene]amino]oxy-N-[(3R)-pyrrolidin-3-yl]acetamide;hydrochloride | 1868174: Inhibition of human recombinant His-tagged FLT3/D835Y mutant expressed in baculovirus expression system incubated for 30 mins in presence of ATP by HTRF analysis | ic50 | 0.0002 | uM |
| 2-[(E)-[2-(5-fluoro-2-hydroxy-1H-indol-3-yl)indol-3-ylidene]amino]oxy-1-piperazin-1-ylethanone;hydrochloride | 1868174: Inhibition of human recombinant His-tagged FLT3/D835Y mutant expressed in baculovirus expression system incubated for 30 mins in presence of ATP by HTRF analysis | ic50 | 0.0002 | uM |
| 2-[(E)-[2-(5-bromo-2-hydroxy-1H-indol-3-yl)indol-3-ylidene]amino]oxy-1-piperazin-1-ylethanone;hydrochloride | 1868174: Inhibition of human recombinant His-tagged FLT3/D835Y mutant expressed in baculovirus expression system incubated for 30 mins in presence of ATP by HTRF analysis | ic50 | 0.0002 | uM |
| N-[(1S,3S)-3-aminocyclopentyl]-3-[6-(furan-3-yl)-1H-benzimidazol-2-yl]-1H-indazole-5-carboxamide | 2143349: Inhibition of recombinant FLT3 D835Y mutant (unknown origin) using peptide substrate incubated for for 30 mins by HTRF assay | ic50 | 0.0002 | uM |
| 2-[7-methoxy-3-[6-[[(3R)-piperidin-3-yl]amino]-2-pyridinyl]imidazo[1,2-a]pyridin-6-yl]propan-2-ol | 2205383: Binding affinity to FLT3 (unknown origin) expressed in Escherichia coli BL21 assessed as dissociation constant by DiscoverX KINOMEscan assay | kd | 0.0002 | uM |
| 3-(6-morpholin-4-yl-1H-benzimidazol-2-yl)-N-(piperidin-3-ylmethyl)-1H-indazole-5-carboxamide | 2143345: Inhibition of recombinant wild type FLT3 kinase domain (unknown origin) using peptide substrate incubated for for 30 mins by HTRF assay | ic50 | 0.0002 | uM |
| N-(3-aminopropyl)-3-(6-pyrrolidin-1-yl-1H-benzimidazol-2-yl)-1H-indazole-5-carboxamide | 2143345: Inhibition of recombinant wild type FLT3 kinase domain (unknown origin) using peptide substrate incubated for for 30 mins by HTRF assay | ic50 | 0.0002 | uM |
| N-(3-amino-2-methylpropyl)-3-(6-morpholin-4-yl-1H-benzimidazol-2-yl)-1H-indazole-5-carboxamide | 2143345: Inhibition of recombinant wild type FLT3 kinase domain (unknown origin) using peptide substrate incubated for for 30 mins by HTRF assay | ic50 | 0.0002 | uM |
CTD chemical–gene interactions
58 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| Sorafenib | increases response to substance, decreases reaction, increases phosphorylation, decreases activity, decreases phosphorylation | 5 |
| ponatinib | decreases activity, decreases reaction, increases phosphorylation, decreases phosphorylation | 4 |
| Arsenic Trioxide | increases expression, affects binding, increases reaction, decreases phosphorylation, increases degradation (+1 more) | 3 |
| Benzo(a)pyrene | affects methylation, decreases expression, increases methylation | 3 |
| sodium arsenite | increases expression, increases phosphorylation | 2 |
| Semaxinib | decreases activity | 2 |
| Tretinoin | affects cotreatment, decreases expression, increases reaction, increases response to substance | 2 |
| 2-hydroxy-1-(2-((9-(4-methylcyclohexyl)-9H-pyrido(4’,3’-4,5)pyrrolo(2,3-d)pyrimidin-2-yl)amino)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl)ethanone | decreases phosphorylation | 1 |
| pexidartinib | decreases activity | 1 |
| RGFP966 | affects reaction, decreases expression, decreases phosphorylation | 1 |
| bisphenol F | affects cotreatment, increases methylation | 1 |
| S63845 | decreases expression, increases reaction | 1 |
| parthenolide | decreases expression, increases reaction | 1 |
| fulvic acid | affects cotreatment, decreases reaction, increases expression | 1 |
| bisphenol A | increases expression | 1 |
| ethyl-p-hydroxybenzoate | decreases expression | 1 |
| terbufos | increases methylation | 1 |
| benzo(e)pyrene | increases methylation | 1 |
| celastrol | decreases expression | 1 |
| bafilomycin A | increases expression, increases degradation, decreases reaction | 1 |
| midostaurin | decreases response to substance, decreases activity | 1 |
| romidepsin | decreases phosphorylation, increases reaction | 1 |
| gedunin | decreases expression | 1 |
| tanespimycin | decreases expression | 1 |
| SU 5614 | decreases activity | 1 |
| D-65476 | affects cotreatment, decreases expression, increases reaction | 1 |
| THRX 165724 | decreases phosphorylation | 1 |
| NSC 23766 | affects response to substance | 1 |
| palbociclib | affects response to substance, decreases expression, decreases phosphorylation | 1 |
| 5-((5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl)-N-(2-hydroxy-3-morpholin-4-ylpropyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide | decreases phosphorylation | 1 |
ChEMBL screening assays
3132 unique, capped per target: 3096 binding, 24 functional, 8 admet, 4 toxicity
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL1003890 | Binding | Inhibition of Flt3 | Discovery of pyrrolopyridine-pyridone based inhibitors of Met kinase: synthesis, X-ray crystallographic analysis, and biological activities. — *J Med Chem* |
| CHEMBL1963779 | Functional | PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: FLT3 | PubChem BioAssay data set |
| CHEMBL3826089 | ADMET | Inhibition of FLT3 (unknown origin) | Discovery of a potent and highly selective transforming growth factor β receptor-associated kinase 1 (TAK1) inhibitor by structure based drug design (SBDD). — *Bioorg Med Chem* |
Cellosaurus cell lines
194 cell lines: 148 cancer cell line, 39 factor-dependent cell line, 4 embryonic stem cell, 2 spontaneously immortalized cell line, 1 transformed cell line
First 10 cell lines (id-ordered, not curated):
| Cellosaurus | Name | Category | Sex |
|---|---|---|---|
| CVCL_0064 | MV4-11 | Cancer cell line | Male |
| CVCL_0138 | ACH-2 | Cancer cell line | Female |
| CVCL_0207 | CCRF-CEM | Cancer cell line | Female |
| CVCL_0614 | Kasumi-6 | Cancer cell line | Male |
| CVCL_0R18 | CEM-TART clone 1A2 | Cancer cell line | Female |
| CVCL_0U11 | CEM/MX1 | Cancer cell line | Female |
| CVCL_1150 | CTV-1 | Cancer cell line | Male |
| CVCL_1B35 | CEM/VM-1 | Cancer cell line | Female |
| CVCL_1E04 | Rev-CEM | Cancer cell line | Female |
| CVCL_1G53 | CEM-GFP | Cancer cell line | Female |
Clinical trials (associated diseases)
Via MONDO — disease-level, not drug-specific.
showing 60 of 300 trials:
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT00199147 | Phase 4 | UNKNOWN | Efficacy of G-CSF-Priming in Elderly AML Patients |
| NCT00304447 | Phase 4 | COMPLETED | Study Evaluating the Effect of Corticosteroids on Mylotarg® Infusion-Related Adverse Events in Patients With Leukemia |
| NCT00464217 | Phase 4 | COMPLETED | Treatment of the Acute Myeloblastic Leukaemia in Patients Over 65 Years |
| NCT00487448 | Phase 4 | COMPLETED | SMD_FLAG-IDA_98: FLAG-IDA in Induction Treatment of High Risk Myelodysplastic Syndromes or Secondary Acute Myeloblastic Leukemia |
| NCT00488709 | Phase 4 | COMPLETED | Fludarabine, Cytarabine, Topotecan in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia |
| NCT00686543 | Phase 4 | COMPLETED | Oral Posaconazole in High Risk Patients With Gastrointestinal Dysfunction (Study P05115) |
| NCT01041040 | Phase 4 | COMPLETED | LAM07: Study to Analyze the Efficacy of a Risk Adapted Treatment Strategy, Including Gemtuzumab Ozogamicin (GO) During Consolidation, for Patients With Acute Myeloid Leukemia (AML) |
| NCT01198054 | Phase 4 | TERMINATED | LENA-LMA-5:Lenalidomide in Acute Myeloid Leukemia (AML) |
| NCT01200355 | Phase 4 | COMPLETED | Posaconazole Versus Micafungin for Prophylaxis Against Invasive Fungal Infections During Neutropenia in Patients Undergoing Chemotherapy for Acute Myelogenous Leukemia, Acute Lymphocytic Leukemia or Myelodysplastic Syndrome |
| NCT01347996 | Phase 4 | COMPLETED | Maintenance Therapy With Ceplene® (Histamine) and IL-2 on Immune Response and MRD in Acute Myeloid Leukemia |
| NCT01587430 | Phase 4 | UNKNOWN | 3 Anthracyclines, 2 Types of Consolidation With Different ARA-C Doses and Maintenance in Adult Acute Myeloid Leukemia |
| NCT01819792 | Phase 4 | COMPLETED | Respiratory Viral Infections During Acute Myeloid Leukemia (AML)Chemotherapy Related Aplasia |
| NCT02024308 | Phase 4 | UNKNOWN | AML1-ETO Acute Myeloid Leukemia With Fludarabine and Cytarabine Chemotherapy |
| NCT02027064 | Phase 4 | UNKNOWN | Interferon for the Intervention of Molecular Relapse in t (8; 21) AML After Allo-HSCT |
| NCT02277847 | Phase 4 | UNKNOWN | Idarubicin at Different Dosages as Induction Therapy for Newly Diagnosed Acute Myeloid Leukaemia |
| NCT02386800 | Phase 4 | ACTIVE_NOT_RECRUITING | CINC424A2X01B Rollover Protocol |
| NCT02926586 | Phase 4 | COMPLETED | Fludarabine and Cytarabine Versus High-dose Cytarabine for CBF-AML |
| NCT02933333 | Phase 4 | UNKNOWN | G-CSF Alone or Combination With GM-CSF on Prevention and Treatment of Infection in Children With Malignant Tumor |
| NCT03026842 | Phase 4 | UNKNOWN | Decitabine Versus Conventional Chemotherapy for Maintenance Therapy of Acute Myeloid Leukemia With t(8;21) |
| NCT03150134 | Phase 4 | UNKNOWN | Early Tapering of Immunosuppressive Agents to Immunomodulation to Improve Survival of AML Patients |
| NCT05144243 | Phase 4 | ACTIVE_NOT_RECRUITING | Study to Assess Adverse Events and Change in Disease State of Oral Venetoclax in Combination With Subcutaneous (SC) Azacitidine in Newly Diagnosed Adult Participants With Acute Myeloid Leukemia (AML) Who Are Ineligible for Intensive Chemotherapy in China |
| NCT06370000 | Phase 4 | RECRUITING | Oral Azacitidine in Transplant-Eligible Patients With Acute Myeloid Leukemia (AML) Suffering From Health-Inequality |
| NCT06571825 | Phase 4 | RECRUITING | RIC Allo-HSCT vs. Venetoclax-Based Consolidation in Elderly AML Patients After First CR |
| NCT07016165 | Phase 4 | RECRUITING | Ciprofloxacin vs Ceftazidime for Empirical Treatment of High-Risk Neutropenic Fever in Children With Hematologic Malignancies |
| NCT07044687 | Phase 4 | RECRUITING | Study to Assess Adverse Events and Change in Disease Activity of Oral Venetoclax in Combination With Subcutaneous (SC) or Intravenous (IV) Azacitidine in Newly Diagnosed Adult Participants With Acute Myeloid Leukemia (AML) Who Are Ineligible for Standard Induction Therapy in India |
| NCT07486713 | Phase 4 | RECRUITING | Olutasidenib DDI Study in Patients With IDH1 Mutation Positive Malignancies |
| NCT07561892 | Phase 4 | RECRUITING | Study of the Effectiveness and Safety of Daunorubicin /Idarubicin ± Silibinin in Treating Newly Diagnosed AML (Non-M3). |
| NCT07773909 | Phase 4 | COMPLETED | Venetoclax With Hypomethylating Agents in Newly Diagnosed AML Unfit for Intensive Chemotherapy |
| NCT00000589 | Phase 3 | COMPLETED | Trial to Reduce Alloimmunization to Platelets (TRAP) |
| NCT00044486 | Phase 3 | COMPLETED | Prophylaxis Trial of Posaconazole Versus Standard Azole Therapy for Neutropenic Patients (Study P01899) |
| NCT00093990 | Phase 3 | COMPLETED | Tipifarnib Versus Best Supportive Care in the Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML) |
| NCT00125606 | Phase 3 | TERMINATED | Phase 3 Trial for AML Patients in CR2 Comparing 8Gy TBI /Fludarabine to Conditioning With TBI 12Gy/Cyclophosphamide |
| NCT00136084 | Phase 3 | COMPLETED | Treatment of Patients With Newly Diagnosed Acute Myeloid Leukemia or Myelodysplasia |
| NCT00146120 | Phase 3 | COMPLETED | Risk-Adapted Therapy of Acute Myeloid Leukemia of Adults (18-60 Years) According to the Cytogenetic Result |
| NCT00150878 | Phase 3 | TERMINATED | Standard vs. Reduced-Intensity Conditioning in Patients With Acute Myeloid Leukemia in First Remission |
| NCT00151255 | Phase 3 | COMPLETED | All-Trans Retinoic Acid in Combination With Standard Induction and Consolidation Therapy in Older Patients With Newly Diagnosed Acute Myeloid Leukemia |
| NCT00152139 | Phase 3 | COMPLETED | Stem Cell Transplantation for Patients With Hematologic Malignancies |
| NCT00152594 | Phase 3 | TERMINATED | Voriconazole or Placebo in the Prophylaxis of Lung Infiltrates in Patients Undergoing Induction Chemotherapy for Acute Myelogenous Leukemia |
| NCT00186966 | Phase 3 | COMPLETED | Treatment of Children and Adolescents With Refractory or Relapsed Acute Myeloid Leukemia |
| NCT00226512 | Phase 3 | WITHDRAWN | To Determine the Role of Adding Campath-1H or ATG Given In-vivo in Addition to Fludarabine and Low Dose Busulfex on Outcome in Patients Treated With Reduced Intensity Conditioning |
| NCT00260832 | Phase 3 | COMPLETED | Trial of Decitabine in Patients With Acute Myeloid Leukemia |
| NCT00266136 | Phase 3 | COMPLETED | Biology and Treatment Strategy of AML in Its Subgroups: Multicenter Randomized Trial by the German Acute Myeloid Leukemia Cooperative Group (AMLCG) |
| NCT00317642 | Phase 3 | COMPLETED | A Study of Clofarabine and Cytarabine for Older Patients With Relapsed or Refractory Acute Myelogenous Leukemia (AML)(CLASSIC I) |
| NCT00322101 | Phase 3 | COMPLETED | Low-Dose or High-Dose Conditioning Followed by Peripheral Blood Stem Cell Transplant in Treating Patients With Myelodysplastic Syndrome or Acute Myelogenous Leukemia |
| NCT00363025 | Phase 3 | TERMINATED | A Randomized Study of Post-Remission Therapy in Elderly Patients With Acute Myelogenous Leukemia. |
| NCT00406393 | Phase 3 | COMPLETED | Sirolimus/Tacrolimus Versus Tacrolimus/Methotrexate for Preventing Graft-Versus-Host Disease (GVHD) (BMT CTN 0402) |
| NCT00412360 | Phase 3 | COMPLETED | Single vs Double Umbilical Cord Blood Transplants in Children With High Risk Leukemia and Myelodysplasia (BMT CTN 0501) |
| NCT00428558 | Phase 3 | COMPLETED | Timed-Sequential Induction in CBF-AML |
| NCT00469144 | Phase 3 | COMPLETED | IV Busulfan With Allo-BMT: Study for Patients With Acute Myelogenous Leukemia and Myelodysplastic Syndrome |
| NCT00474006 | Phase 3 | COMPLETED | High Dose Daunorubicin Vs. Standard Dose Daunorubicin in Induction Treatment of AML |
| NCT00476541 | Phase 3 | COMPLETED | NOPHO-AML 2004 Study for Children With Acute Myeloid Leukemia |
| NCT00480064 | Phase 3 | COMPLETED | Lomustine and Intermediate Dose Cytarabine in Older Patients With AML |
| NCT00495287 | Phase 3 | COMPLETED | A Remission Induction Therapy and Risk-oriented Postremission Strategy for Adult Acute Myelogenous Leukemia (AML) |
| NCT00513305 | Phase 3 | TERMINATED | Cytarabine in Combination With Arsenic Trioxide vs. Cytarabine Alone in Elderly Patients With Acute Myeloid Leukemia |
| NCT00568633 | Phase 3 | TERMINATED | Allogeneic HCT Using Nonmyeloablative Host Conditioning With TLI & ATG vs SOC in AML |
| NCT00589082 | Phase 3 | COMPLETED | DaunoXome + Ara-C vs Daunorubicin + Ara-C in Elderly AML |
| NCT00590837 | Phase 3 | COMPLETED | Adding Lomustine to Chemotherapy in Older Patients With Acute Myelogenous Leukemia (AML), and Allogeneic Transplantation for Patients From 60 to 65 Years Old |
| NCT00606723 | Phase 3 | COMPLETED | Allogenic Stem Cell Transplantation for Children, Adolescents and Young Adults With Relapsed or Refractory AML |
| NCT00656448 | Phase 3 | COMPLETED | A Randomized Trial of Procrit vs. No Procrit in AML and High Risk MDS |
| NCT00678275 | Phase 3 | COMPLETED | Chronic Graft-versus-host Disease (cGvHD) Prophylaxis With or Without ATG Prior to Stem Cell Transplantation (SCT) From HLA-identical Siblings in Patients With Acute Leukemia |
Predicted chemistry — Sugi Predict
The predicted patent-compound landscape for FLT3 across ~30M SureChEMBL compounds — explore on Sugi Predict.
Related Atlas pages
- Associated diseases: leukemia, acute myeloid, susceptibility to, acute myeloid leukemia, colorectal cancer, acute promyelocytic leukemia, renal cell carcinoma
- Biomarker drugs (CIViC) (drugs whose response is associated with variants in this gene — CIViC predictive evidence, not targeting): Gilteritinib, Midostaurin, Sorafenib, Pexidartinib, Nilotinib, Sunitinib, Lestaurtinib, Pacritinib, Quizartinib, Selumetinib, Tretinoin, Regorafenib
- Targeted by drugs: Cediranib, Ceritinib, CM-082, Crenolanib, Dovitinib, Famitinib, Fedratinib, Gilteritinib, Lestaurtinib, Linifanib, Midostaurin, Pacritinib, Pexidartinib, Quizartinib, Ruserontinib, Sitravatinib, Sorafenib, Sunitinib
- Disease cohort memberships (association, not causation — diseases whose associated-gene cohort lists this gene; a subset are also under Associated diseases): acute lymphoblastic leukemia, acute myeloblastic leukemia without maturation, acute myeloid leukemia, acute myeloid leukemia by FAB classification, acute myeloid leukemia with minimal differentiation, acute myeloid leukemia with mutated NPM1, acute promyelocytic leukemia, atypical chronic myeloid leukemia, BCR-ABL1 negative, B-cell adult acute lymphocytic leukemia, B-lymphoblastic leukemia/lymphoma with t(9;22)(q34.1;q11.2), cancer, childhood leukemia, childhood myelodysplastic syndrome, colorectal carcinoma, leukemia, leukemia, acute myeloid, susceptibility to, mixed phenotype acute leukemia with t(9;22)(q34.1;q11.2), myelodysplastic syndrome, nonpapillary renal cell carcinoma, plasma cell myeloma, renal cell adenocarcinoma, renal cell carcinoma