FLT1

Summary

FLT1 (fms related receptor tyrosine kinase 1, HGNC:3763) is a protein-coding gene on chromosome 13q12.3, encoding Vascular endothelial growth factor receptor 1 (P17948). Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell survival, cell migration, macrophage function, chemotaxis, and cancer cell invasio….

This gene encodes a member of the vascular endothelial growth factor receptor (VEGFR) family. VEGFR family members are receptor tyrosine kinases (RTKs) which contain an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and a tyrosine kinase (TK) domain within the cytoplasmic domain. This protein binds to VEGFR-A, VEGFR-B and placental growth factor and plays an important role in angiogenesis and vasculogenesis. Expression of this receptor is found in vascular endothelial cells, placental trophoblast cells and peripheral blood monocytes. Multiple transcript variants encoding different isoforms have been found for this gene. Isoforms include a full-length transmembrane receptor isoform and shortened, soluble isoforms. The soluble isoforms are associated with the onset of pre-eclampsia.

Source: NCBI Gene 2321 — RefSeq curated summary.

At a glance

• GWAS associations: 18
• Clinical variants (ClinVar): 198 total
• Regional missense constraint (gnomAD): 1 of 3 regions constrained (≈1% of expected missense variation)
• GTEx eGene: eQTL in 6 tissues, sQTL in 11 (q < 0.05)
• Phenotypes (HPO): 27
• Drug target: yes — 5 curated mechanism-of-action drugs, 40 via a complex or family; 77 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 1 — Sunitinib
• Approved drugs acting on a complex or family including it: 9 — Axitinib, Fruquintinib, Lenvatinib Mesylate, +6 more (Vascular endothelial growth factor receptor)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.38 (moderately constrained)
• MANE Select transcript: NM_002019
• Notable: 198 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3763
Approved symbol	FLT1
Name	fms related receptor tyrosine kinase 1
Location	13q12.3
Locus type	gene with protein product
Status	Approved
Aliases	VEGFR1
Ensembl gene	ENSG00000102755
Ensembl biotype	protein_coding
OMIM	165070
Entrez	2321

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 9 protein_coding, 5 protein_coding_CDS_not_defined, 3 nonsense_mediated_decay

MANE Select: ENST00000282397

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 8, TSL 5: 1

ENST00000282397, ENST00000539099, ENST00000540678, ENST00000541932, ENST00000543394, ENST00000615611, ENST00000615840, ENST00000617835, ENST00000639477, ENST00000706527, ENST00000909997, ENST00000909998, ENST00000909999, ENST00000910000, ENST00001003174, ENST00001069434, ENST00001131755

RefSeq mRNA: 4 — MANE Select: NM_002019 NM_001159920, NM_001160030, NM_001160031, NM_002019

CCDS: CCDS53860, CCDS53861, CCDS73556, CCDS9330

Canonical transcript exons

ENST00000282397 — 30 exons

Exon	Start	End
ENSE00000679735	28396960	28397068
ENSE00000679737	28405780	28405894
ENSE00000906624	28427159	28427318
ENSE00000906625	28427752	28427921
ENSE00000906626	28430050	28430167
ENSE00000906628	28433819	28433955
ENSE00000906629	28434058	28434220
ENSE00000906630	28438221	28438345
ENSE00000938500	28467521	28467617
ENSE00000938501	28466903	28467129
ENSE00001005678	28357554	28357685
ENSE00001005684	28384885	28385031
ENSE00001005702	28389796	28390104
ENSE00001157319	28300346	28303368
ENSE00002213859	28494780	28495128
ENSE00002708125	28431136	28431310
ENSE00003530328	28345445	28345551
ENSE00003722277	28339168	28339300
ENSE00003722836	28322790	28322946
ENSE00003724682	28308843	28308927
ENSE00003725840	28311590	28311732
ENSE00003726866	28321463	28321585
ENSE00003727886	28334025	28334129
ENSE00003732168	28329615	28329728
ENSE00003733226	28311993	28312098
ENSE00003733403	28327462	28327550
ENSE00003735431	28317498	28317597
ENSE00003745304	28306678	28306772
ENSE00003749850	28322262	28322359
ENSE00003753629	28319423	28319534

Expression profiles

Bgee: expression breadth ubiquitous, 277 present calls, max score 97.56.

FANTOM5 (CAGE): breadth broad, TPM avg 15.6103 / max 5175.5927, expressed in 767 samples.

Highest expression (Bgee): pericardium, placenta, endothelial cell, heart right ventricle, ventricle myocardium.

Genetic regulation across tissues (GTEx eQTL / sQTL)

FLT1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 6 tissues and its splicing (sQTL) in 11 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

17 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	sqtl	5.9e-09	+0.40	13:28312790:A:C
Adipose Visceral Omentum	sqtl	1.1e-08	+0.41	13:28312790:A:C
Adipose Subcutaneous	sqtl	1.5e-08	+0.39	13:28312790:A:C
Lung	sqtl	6.8e-08	+0.43	13:28312790:A:C
Nerve Tibial	sqtl	8.9e-06	+0.37	13:28312790:A:C
Whole Blood	eqtl	1.0e-04	-0.18	13:28465734:G:T
Testis	eqtl	1.5e-04	+0.23	13:28308334:G:A
Heart Atrial Appendage	sqtl	1.2e-03	+0.36	13:28312790:A:C
Breast Mammary Tissue	sqtl	1.4e-03	+0.33	13:28312790:A:C
Cells Cultured fibroblasts	eqtl	2.4e-03	+0.61	13:28585210:C:G
Colon Transverse	sqtl	8.2e-03	+0.33	13:28309373:C:T
Testis	sqtl	1.1e-02	-0.21	13:28309200:A:G
Brain Hypothalamus	sqtl	1.1e-02	-1.86	13:27766979:A:G
Colon Transverse	eqtl	2.2e-02	-0.60	13:29025586:A:G
Esophagus Muscularis	sqtl	3.2e-02	+0.24	13:28312790:A:C
Brain Hippocampus	eqtl	3.7e-02	+0.41	13:28376670:G:C
Brain Cerebellar Hemisphere	eqtl	3.9e-02	+0.30	13:28414388:T:A

FANTOM5 promoters

showing 10 of 12 alternative TSS:

Promoter ID	TPM avg	Samples expressed
136577	15.2105	750
136539	0.1036	9
136578	0.0675	24
136535	0.0528	22
136557	0.0330	5
136533	0.0279	3
136538	0.0262	4
136537	0.0247	5
136534	0.0244	7
136540	0.0167	2

Top tissues by expression

showing 100 of 294 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
pericardium	UBERON:0002407	97.56	gold quality
placenta	UBERON:0001987	96.49	gold quality
endothelial cell	CL:0000115	95.49	gold quality
heart right ventricle	UBERON:0002080	94.18	gold quality
left ventricle myocardium	UBERON:0006566	93.52	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	93.47	gold quality
cardia of stomach	UBERON:0001162	93.10	gold quality
thyroid gland	UBERON:0002046	93.01	gold quality
left lobe of thyroid gland	UBERON:0001120	92.87	gold quality
medial globus pallidus	UBERON:0002477	92.69	gold quality
right lobe of thyroid gland	UBERON:0001119	92.49	gold quality
vena cava	UBERON:0004087	92.46	gold quality
omental fat pad	UBERON:0010414	92.23	gold quality
peritoneum	UBERON:0002358	92.19	gold quality
metanephric glomerulus	UBERON:0004736	92.03	gold quality
renal medulla	UBERON:0000362	91.94	gold quality
adipose tissue of abdominal region	UBERON:0007808	91.86	gold quality
renal glomerulus	UBERON:0000074	91.72	gold quality
myocardium	UBERON:0002349	91.26	gold quality
globus pallidus	UBERON:0001875	91.06	gold quality
colonic epithelium	UBERON:0000397	90.99	gold quality
cardiac ventricle	UBERON:0002082	90.93	gold quality
heart left ventricle	UBERON:0002084	90.78	gold quality
adipose tissue	UBERON:0001013	90.03	gold quality
subcutaneous adipose tissue	UBERON:0002190	89.83	gold quality
inferior vagus X ganglion	UBERON:0005363	89.56	gold quality
connective tissue	UBERON:0002384	89.53	gold quality
apex of heart	UBERON:0002098	89.47	gold quality
heart	UBERON:0000948	89.41	gold quality
metanephros	UBERON:0000081	89.38	gold quality
inferior olivary complex	UBERON:0002127	89.28	gold quality
cardiac atrium	UBERON:0002081	89.01	gold quality
subthalamic nucleus	UBERON:0001906	88.96	gold quality
visceral pleura	UBERON:0002401	88.95	gold quality
substantia nigra	UBERON:0002038	88.94	gold quality
cortex of kidney	UBERON:0001225	88.93	gold quality
pylorus	UBERON:0001166	88.91	gold quality
cardiac muscle of right atrium	UBERON:0003379	88.82	gold quality
right atrium auricular region	UBERON:0006631	88.77	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	88.67	gold quality
midbrain	UBERON:0001891	88.61	gold quality
adrenal tissue	UBERON:0018303	88.43	gold quality
upper lobe of lung	UBERON:0008948	87.77	gold quality
upper lobe of left lung	UBERON:0008952	87.73	gold quality
kidney	UBERON:0002113	87.56	gold quality
lower lobe of lung	UBERON:0008949	87.53	gold quality
spinal cord	UBERON:0002240	87.35	gold quality
choroid plexus epithelium	UBERON:0003911	87.13	gold quality
putamen	UBERON:0001874	86.96	gold quality
biceps brachii	UBERON:0001507	86.94	gold quality
gall bladder	UBERON:0002110	86.87	gold quality
myometrium	UBERON:0001296	86.86	gold quality
substantia nigra pars reticulata	UBERON:0001966	86.84	gold quality
medulla oblongata	UBERON:0001896	86.77	gold quality
adult mammalian kidney	UBERON:0000082	86.71	gold quality
deltoid	UBERON:0001476	86.49	silver quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	86.37	gold quality
skeletal muscle tissue	UBERON:0001134	86.36	gold quality
right lung	UBERON:0002167	86.32	gold quality
body of tongue	UBERON:0011876	86.30	gold quality
muscle tissue	UBERON:0002385	86.18	gold quality
gastrocnemius	UBERON:0001388	86.15	gold quality
lung	UBERON:0002048	86.15	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	86.14	gold quality
caudate nucleus	UBERON:0001873	86.11	gold quality
muscle of leg	UBERON:0001383	86.10	gold quality
calcaneal tendon	UBERON:0003701	86.09	gold quality
pleura	UBERON:0000977	86.00	gold quality
triceps brachii	UBERON:0001509	85.94	silver quality
amygdala	UBERON:0001876	85.93	gold quality
islet of Langerhans	UBERON:0000006	85.90	gold quality
seminal vesicle	UBERON:0000998	85.80	gold quality
muscle organ	UBERON:0001630	85.68	gold quality
hindlimb stylopod muscle	UBERON:0004252	85.68	gold quality
skeletal muscle organ	UBERON:0014892	85.67	gold quality
kidney epithelium	UBERON:0004819	85.66	gold quality
gluteal muscle	UBERON:0002000	85.56	silver quality
ventral tegmental area	UBERON:0002691	85.56	gold quality
lateral nuclear group of thalamus	UBERON:0002736	85.56	gold quality
dorsal plus ventral thalamus	UBERON:0001897	85.43	gold quality
hypothalamus	UBERON:0001898	85.29	gold quality
substantia nigra pars compacta	UBERON:0001965	85.15	gold quality
Ammon’s horn	UBERON:0001954	85.09	gold quality
superior vestibular nucleus	UBERON:0007227	85.06	gold quality
parietal pleura	UBERON:0002400	84.56	gold quality
jejunum	UBERON:0002115	84.31	gold quality
body of uterus	UBERON:0009853	84.31	gold quality
tongue	UBERON:0001723	84.10	gold quality
layer of synovial tissue	UBERON:0007616	83.99	gold quality
superficial temporal artery	UBERON:0001614	83.86	gold quality
metanephros cortex	UBERON:0010533	83.80	gold quality
temporal lobe	UBERON:0001871	83.58	gold quality
pons	UBERON:0000988	83.43	gold quality
cingulate cortex	UBERON:0003027	83.36	gold quality
postcentral gyrus	UBERON:0002581	83.28	gold quality
telencephalon	UBERON:0001893	83.26	gold quality
right frontal lobe	UBERON:0002810	83.13	gold quality
mammary gland	UBERON:0001911	83.07	gold quality
thoracic mammary gland	UBERON:0005200	83.07	gold quality
anterior cingulate cortex	UBERON:0009835	83.06	gold quality

Single-cell (SCXA)

Detected in 28 experiment(s), a significant marker in 28.

Experiment	Marker?	Max mean expression
E-MTAB-6678	yes	5082.60
E-GEOD-135922	yes	4945.01
E-GEOD-131882	yes	4934.48
E-HCAD-35	yes	3901.03
E-HCAD-23	yes	3580.07
E-MTAB-6701	yes	3488.49
E-CURD-119	yes	3254.58
E-GEOD-180759	yes	3193.30
E-MTAB-11268	yes	2824.07
E-HCAD-25	yes	2560.55
E-HCAD-31	yes	2200.74
E-HCAD-30	yes	2067.95
E-GEOD-83139	yes	1674.01
E-MTAB-5061	yes	1504.96
E-MTAB-8205	yes	1167.72

HPA expression

RNA tissue specificity: Tissue enriched

showing 60 of 76 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Placenta	tissue	394.3	medium
Retina	tissue	46.2
Cerebral cortex	tissue	44.9	low
Occipital cortex	tissue	44.9
Somatosensory cortex	tissue	44.3
Thyroid gland	tissue	43.8	not detected
Putamen	tissue	43.7
Motor cortex	tissue	43.6
Superior colliculi	tissue	43.5
Insular cortex	tissue	43.1
Thalamus	tissue	42.8
Substantia nigra	tissue	41.7
Prefrontal cortex	tissue	39.9
Hippocampus	tissue	39.7	not detected
Pons	tissue	38.9
Midbrain	tissue	38.6
Hippocampal formation	tissue	37.4
Entorhinal cortex	tissue	37.4
Medulla oblongata	tissue	37.1
Retrosplenial cortex	tissue	36.9
Temporal cortex	tissue	36.3
Retrosplenial and cingulate cortex	tissue	36.1
Postcentral gyrus	tissue	35.8
Tongue	tissue	35.7
Spinal cord	tissue	34.5
Locus coeruleus	tissue	32.5
Ventral forebrain	tissue	32.1
Choroid plexus	tissue	30.9
Basal ganglia	tissue	30.3	not detected
Amygdala	tissue	29.0
Corpus callosum	tissue	29.0
Adipose tissue	tissue	28.3	not detected
Nucleus accumbens	tissue	28.0
Hypothalamus	tissue	27.8
Heart muscle	tissue	27.3	low
Parathyroid gland	tissue	27.0	not detected
Septum	tissue	26.6
Periaqueductal gray	tissue	25.7
Olfactory bulb	tissue	23.2
Caudate putamen	tissue	22.5
Frontal cortex	tissue	19.8
Kidney	tissue	19.8	not detected
Cerebellum	tissue	18.7	not detected
Skeletal muscle	tissue	17.6	low
Spleen	tissue	16.8	not detected
Liver	tissue	16.4	not detected
Smooth muscle	tissue	15.7	medium
Endometrium 1	tissue	15.0	not detected
Gallbladder	tissue	14.8	not detected
Cervix	tissue	14.1	not detected
Urinary bladder	tissue	12.6	not detected
Lung	tissue	12.3	high
Pancreas	tissue	10.4	not detected
Stomach 1	tissue	9.8	not detected
Vagina	tissue	9.4	not detected
Seminal vesicle	tissue	9.3	not detected
Pituitary gland	tissue	8.8
Prostate	tissue	8.3	not detected
Adrenal gland	tissue	7.8	not detected
Fallopian tube	tissue	7.5	not detected

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Posterior thalamic nucleus (84.7), Dorsal cochlear nucleus (68.4), Reticulotegmental nucleus (60.2), Area parastriata, superior (58.3), Nucleus cuneatus (58.1).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets:

Target	Regulation
PHACTR1	Activation
PTGIR

Upstream regulators (CollecTRI, top): ADM2, AP1, ARNT, ATF1, ATF2, CREB1, DDIT3, DLL4, E2F1, EGR1, EPAS1, ESR1, ETS1, FOS, GLI2, HHEX, HIF1A, HSF1, JARID2, JUN, MYC, NKX2-1, NR2F2, PDCD10, PPARG, SP1, SP3, SP4, TAL1, TCF3, TP53, TP63, TP73, ZNF354C

miRNA regulators (miRDB)

Targeting FLT1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 119 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-12121	99.99	66.64	255
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-17-5P	99.89	73.83	2665

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.379, missense Z 2.96 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000282397 splits into 3 regions with different missense tolerance; 1 is missense-constrained (≈1% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
13:28,303,170–28,321,506	329 / 366.2	0.90	no
13:28,321,507–28,321,545	2 / 16.2	0.12	yes (p 4.3e-04)
13:28,321,546–28,494,843	991 / 1254.8	0.79	no

Literature-anchored findings (GeneRIF, showing 40)

• vitronectin increased the presence of all four growth factor receptors and most notably, VEGFR-1; in contrast, fibrin decreased all four receptors, especially FGFR-1 and FGFR-2 (PMID:11693202)
• presence of an sVEGFR-1 in human serum and plasma of normal male and female donors strongly suggests that it plays an important role as a naturally occurring VEGF antagonist in the regulation and availability of VEGF-mediated biological activities in vivo (PMID:11806246)
• A potential mechanism involved in hemangioma formation is the alteration of the FLT1 receptor signaling pathway in endothelial and/or pericytic cells. (PMID:11807987)
• Effect of placenta growth factor-1 on proliferation and release of nitric oxide, cyclic AMP and cyclic GMP in human epithelial cells expressing the FLT-1 receptor (PMID:11811792)
• Involvement of VEGFR-2 (kdr/flk-1) but not VEGFR-1 (flt-1) in VEGF-A and VEGF-C-induced tube formation by human microvascular endothelial cells in fibrin matrices in vitro. (PMID:11824379)
• VEGF and flt-1 are upregulated in blood vessels in many organs of acute Kawasaki Disease (PMID:11839635)
• In this study we give evidence of Flt-1 and KDR receptors in platelets. (PMID:11852061)
• expression, purification and detection of biological activity (PMID:11862609)
• Overexpression of Flt-Ig significantly inhibited the growth of K562 leukemia cells. (PMID:11877075)
• VEGF, Flt1, and Flk1 can be considered as indicators of the malignancy potential of diffusely infiltrating astrocytomas. The expression of VEGF and the two receptors may be affected by the proliferative activity of tumor cells. (PMID:11908876)
• CLL B cells consistently express VEGFR1 mRNA; co-expression of angiogenic molecules and receptors suggest autocrine pathways of stimulation. (PMID:11986954)
• Placental growth factor promotes recruitment of VEGFR1(+) hematopoietic stem cells from a quiescent to a proliferative bone marrow microenvironment, favoring differentiation, mobilization and reconstitution of hematopoiesis. (PMID:12091880)
• Expression of vascular endothelial growth factor and its receptor (Flt-1) in breast carcinoma (PMID:12133473)
• results suggest that in the hematopoietic microenvironment an autocrine vascular endothelial growth factor loop contributes to optimal megakaryocytic maturation through Flt1 (PMID:12406876)
• In human umbilical vein endothelial cells, the Flt-1 receptor appears to act as a decoy receptor, tempering the response to lower concentrations of VEGF. (PMID:12426207)
• The expression of vascular endothelial growth factor and its receptors KDR and Flt-1 by gastric carcinoma tissues and cell lines was detected to elucidate the molecular mechanism of this growth factor in promoting tumor growth. (PMID:12439912)
• This protein is a novel therapeutic target for angiogenic disorders (REVIEW) (PMID:12543719)
• Staining for the receptors VEGFR-1 and VEGFR-2 was positive in large lymphoid cells in stage IV non-Hodgkin lymphoma. (PMID:12607599)
• expression system is involved in angiogenesis in inflamed synovial tissue in the temporomandibular joint (PMID:12651930)
• VEGF secreted by retinal pigment epithelial cells upregulates pigment epithelium-derived factor expression via VEGFR-1 in an autocrine manner. (PMID:12670505)
• findings may point to an involvement of soluble vascular endothelial growth factor receptor-1 in the pathophysiology of preeclampsia possibly by antagonizing vascular endothelial growth factor effects (PMID:12727995)
• Aberrant methylation of the vascular endothelial growth factor receptor-1 gene is associated with prostate cancer (PMID:12824880)
• VEGFR-1 secreted by endothelial cells becomes a matrix-associated protein that is able to interact with the alpha 5 beta 1 integrin; a new role of VEGFR-1 in angiogenesis (PMID:12865438)
• in humans: 1) VEGF, KDR, and Flt-1 mRNA are increased by acute systemic exercise; 2) the time course of the VEGF, KDR, and Flt-1 mRNA responses are different from those previously reported in rats (PMID:12949011)
• Postmortem brain tissue analysis demonstrates VEGFR1 localized as paracellular deposits in Durck’s granulomas of patients with cerebral malaria. (PMID:14512169)
• mRNA expression of VEGF and its receptor flt-1 in the hydrosalpinx was significantly higher than that in the healthy oviduct. (PMID:14585871)
• overproduction of soluble VEGFR-1 may lead to suppression of VEGF-A and PlGF and the down-regulation of its membrane bound form (VEGFR-1) in the placental bed, may result in the defective uteroplacental development. (PMID:14602804)
• Data suggest that vascular endothelial growth factor (VEGF) receptor flt-1 is expressed by eosinophils whose activation with VEGF stimulates directed migration and release of eosinophil cationic protein. (PMID:14607815)
• VEGF, VEGFR-1 and VEGFR-2 are concomitantly expressed in pre-B ALL cells. Expression of the receptors is limited to the intra-cytoplasmic compartment and may suggest either internalization or a block in trafficking of the receptor to the surface. (PMID:14654077)
• changing of transcriptional activity of VEGF gene and its receptor FLT-1 indicates an autocrine mechanism of regulation of angiogenic gene activity in the first step of carcinogenesis–low-grade intraepithelial lesions of the uterine cervix (PMID:14674128)
• crystal structure of placental growth factor in complex with domain 2 of vascular endothelial growth factor receptor-1 (PMID:14684734)
• Specific VEGFR1 expression, examined in 27 B-CLL samples, was positive in all of them. The VEGF transduction pathway may be very active in CLL cells. Both its paracrine & autocrine pathways may contribute to their enhanced survival. (PMID:14687619)
• in systemic lupus erythematosus patients the levels of VEGF and sVEGFR-1 are higher in patients with active SLE than in inactive disease or healthy persons (PMID:14760936)
• flt-1 appears to be important in the temporal regulation of oviductal secretion. (PMID:14967383)
• VEGF receotor signaling regulates survival signals in CLL cells and that interruption of this autocrine pathway results in caspase activation and subsequent leukemic cell death. (PMID:14996703)
• vascular endothelial growth factor (VEGF) is strongly expressed in villous cytotrophoblast cells and subsequently in Hofbauer cells while its receptors Flt-1 and Flk-1 are found on vasculogenic and angiogenic precursor cells (PMID:15135240)
• C-Myc over-expression was significantly associated with high sVEGF and normal sFlt-1 level in DLBCL patients, suggesting a complex interrelationship between c-Myc oncogene expression and angiogenic regulators (PMID:15160911)
• Increased expression of FLT1 is associated with an aggressive angiogenic phenotype in melanoma. (PMID:15166498)
• VEGFR1 initiates a clonogenic response in myeloid leukemia cells that is PI3-kinase dependent. (PMID:15183893)
• a basis for understanding molecular recognition between PlGF-1 and VEGFR1 (PMID:15272021)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	flt1	ENSDARG00000019371
mus_musculus	Flt1	ENSMUSG00000029648
rattus_norvegicus	Flt1	ENSRNOG00000000940

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), MET (ENSG00000105976), EPHB6 (ENSG00000106123), PDGFRB (ENSG00000113721), EPHA4 (ENSG00000116106), TEK (ENSG00000120156), FLT3 (ENSG00000122025), 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:95558) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 28 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal vascular development	2
abnormal blood vessel morphology	2
abnormal embryo development	2
embryonic growth arrest	2
abnormal dorsal aorta morphology	2
increased angiogenesis	2
abnormal heart development	1
decreased body size	1
abnormal embryo turning	1
disorganized yolk sac vascular plexus	1
abnormal sensory capabilities/reflexes/nociception	1
abnormal blood circulation	1
decreased myocardial infarct size	1
increased vascular permeability	1
neuron degeneration	1
abnormal vitelline vasculature morphology	1
abnormal physiological neovascularization	1
impaired macrophage chemotaxis	1
abnormal embryonic erythrocyte morphology	1
increased response of heart to induced stress	1
increased macrophage cell number	1
cornea vascularization	1
abnormal vascular endothelial cell morphology	1
embryonic lethality during organogenesis, complete penetrance	1
embryonic lethality during organogenesis, incomplete penetrance	1

+3 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
Pan troglodytes	Q4VSN5	99.5%	Diamond
Bos taurus	P43481	99.4%	Diamond
Capra hircus	Q28317	99.4%	Diamond
Felis catus	Q28889	99.2%	Diamond
Macaca mulatta	Q20CR4	98.9%	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
Coturnix coturnix	Q90330	81.0%	Diamond
Xenopus laevis	P22182	80.6%	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-AS1	ncRNA	100288730
PAN3	protein-coding	255967
POMP	protein-coding	51371
FLT3	protein-coding	2322

Protein

Protein identifiers

Vascular endothelial growth factor receptor 1 — P17948 (reviewed: P17948)

Alternative names: Fms-like tyrosine kinase 1, Tyrosine-protein kinase FRT, Tyrosine-protein kinase receptor FLT, Vascular permeability factor receptor

All UniProt accessions (3): A0A1W2PNW4, P17948, L7RSL3

UniProt curated annotations — full annotation on UniProt →

Function. Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell survival, cell migration, macrophage function, chemotaxis, and cancer cell invasion. Acts as a positive regulator of postnatal retinal hyaloid vessel regression. May play an essential role as a negative regulator of embryonic angiogenesis by inhibiting excessive proliferation of endothelial cells. Can promote endothelial cell proliferation, survival and angiogenesis in adulthood. Its function in promoting cell proliferation seems to be cell-type specific. Promotes PGF-mediated proliferation of endothelial cells, proliferation of some types of cancer cells, but does not promote proliferation of normal fibroblasts (in vitro). Has very high affinity for VEGFA and relatively low protein kinase activity; may function as a negative regulator of VEGFA signaling by limiting the amount of free VEGFA and preventing its binding to KDR. Modulates KDR signaling by forming heterodimers with KDR. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate and the activation of protein kinase C. Mediates phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase, leading to activation of phosphatidylinositol kinase and the downstream signaling pathway. Mediates activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. Phosphorylates SRC and YES1, and may also phosphorylate CBL. Promotes phosphorylation of AKT1 at ‘Ser-473’. Promotes phosphorylation of PTK2/FAK1. Phosphorylates PLCG. May function as decoy receptor for VEGFA. May function as decoy receptor for VEGFA. May function as decoy receptor for VEGFA. Has a truncated kinase domain; it increases phosphorylation of SRC at ‘Tyr-418’ by unknown means and promotes tumor cell invasion.

Subunit / interactions. Interacts with VEGFA, VEGFB and PGF. Monomer in the absence of bound VEGFA, VEGFB or PGF. Homodimer in the presence of bound VEGFA, VEGFB and PGF. Can also form a heterodimer with KDR. Interacts (when tyrosine phosphorylated) with CBL, CRK, GRB2, NCK1, PIK3R1, PLCG, PSEN1 and PTPN11. Probably also interacts with PTPRB. Interacts with RACK1. Identified in a complex with CBL and CD2AP.

Subcellular location. Cell membrane. Endosome Secreted Secreted Secreted Cytoplasm Cytoplasm Cytoplasm.

Tissue specificity. Detected in normal lung, but also in placenta, liver, kidney, heart and brain tissues. Specifically expressed in most of the vascular endothelial cells, and also expressed in peripheral blood monocytes. Isoform 2 is strongly expressed in placenta. Isoform 3 is expressed in corneal epithelial cells (at protein level). Isoform 3 is expressed in vascular smooth muscle cells (VSMC).

Post-translational modifications. N-glycosylated. Ubiquitinated after VEGFA-mediated autophosphorylation, leading to proteolytic degradation. Autophosphorylated on tyrosine residues upon ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Phosphorylation at Tyr-1169 is important for interaction with PLCG. Phosphorylation at Tyr-1213 is important for interaction with PIK3R1, PTPN11, GRB2, and PLCG. Phosphorylation at Tyr-1333 is important for endocytosis and for interaction with CBL, NCK1 and CRK. Is probably dephosphorylated by PTPRB.

Disease relevance. Can contribute to cancer cell survival, proliferation, migration, and invasion, and tumor angiogenesis and metastasis. May contribute to cancer pathogenesis by promoting inflammatory responses and recruitment of tumor-infiltrating macrophages. Abnormally high expression of soluble isoforms (isoform 2, isoform 3 or isoform 4) may be a cause of preeclampsia.

Activity regulation. Present in an inactive conformation in the absence of bound ligand. Binding of VEGFA, VEGFB or PGF leads to dimerization and activation by autophosphorylation on tyrosine residues.

Domain organisation. The second and third Ig-like C2-type (immunoglobulin-like) domains are sufficient for VEGFA binding.

Induction. Up-regulated in coculture of VSMC/endothelial cell (EC) or by direct exposure to VEGF of VSMC monoculture. Up-regulated from the second trimester of pregnancy to the term and in the placenta of women with preeclampsia (PE). Up-regulated in monocytes exposed to bacterial lipopolysaccharide (LPS).

Similarity. Belongs to the protein kinase superfamily. Tyr protein kinase family. CSF-1/PDGF receptor subfamily.

Isoforms (8)

UniProt ID	Names	Canonical?
P17948-1	1, Flt1	yes
P17948-2	2, sFlt1
P17948-3	3, sFlt1-14
P17948-4	4
P17948-5	5, i15
P17948-6	6, i18
P17948-7	7, i21
P17948-8	8

RefSeq proteins (4): NP_001153392, NP_001153502, NP_001153503, NP_002010* (*=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
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR009135	VEGFR1_rcpt	Family
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR013098	Ig_I-set	Domain
IPR013106	Ig_V-set	Domain
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
IPR041348	VEGFR-2_TMD	Domain
IPR050122	RTK	Family
IPR055229	VEGFR1-3_5th	Domain
IPR055238	VEGFR1-3_N_Ig-like	Domain

Pfam: PF00047, PF07679, PF07714, PF13927, PF17988, PF21339, PF22854, PF22971

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 (125 total): strand 20, helix 20, glycosylation site 13, splice variant 11, sequence variant 9, mutagenesis site 9, domain 8, modified residue 8, turn 6, disulfide bond 6, sequence conflict 3, compositionally biased region 2, binding site 2, topological domain 2, signal peptide 1, chain 1, region of interest 1, active site 1, site 1, transmembrane region 1

Structure

Experimental structures (PDB)

12 structures by resolution:

PDB	Title	Method	Resolution (Å)
1FLT	VEGF IN COMPLEX WITH DOMAIN 2 OF THE FLT-1 RECEPTOR	X-RAY DIFFRACTION	1.7
5ABD	CRYSTAL STRUCTURE OF VEGFR-1 DOMAIN 2 IN PRESENCE OF CU	X-RAY DIFFRACTION	2
4CL7	Crystal structure of VEGFR-1 domain 2 in presence of Cobalt	X-RAY DIFFRACTION	2
4CKV	Crystal structure of VEGFR-1 domain 2 in presence of Zn	X-RAY DIFFRACTION	2.06
5EX3	Crystal structure of human SMYD3 in complex with a VEGFR1 peptide	X-RAY DIFFRACTION	2.41
1RV6	Crystal Structure of PlGF in Complex with Domain 2 of VEGFR1	X-RAY DIFFRACTION	2.45
1QTY	VASCULAR ENDOTHELIAL GROWTH FACTOR IN COMPLEX WITH DOMAIN 2 OF THE FLT-1 RECEPTOR	X-RAY DIFFRACTION	2.7
3HNG	Crystal structure of VEGFR1 in complex with …	X-RAY DIFFRACTION	2.7
2XAC	Structural Insights into the Binding of VEGF-B by VEGFR-1D2: Recognition and Specificity	X-RAY DIFFRACTION	2.71
5T89	Crystal structure of VEGF-A in complex with VEGFR-1 domains D1-6	X-RAY DIFFRACTION	4
1QSV	THE VEGF-BINDING DOMAIN OF FLT-1, 20 NMR STRUCTURES	SOLUTION NMR
1QSZ	THE VEGF-BINDING DOMAIN OF FLT-1 (MINIMIZED MEAN)	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P17948-F1	72.86	0.31

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, Tyr protein kinases, Predicted membrane proteins, Predicted secreted proteins, Plasma proteins, RAS pathway related proteins, Cancer-related genes, Candidate cancer biomarkers, Disease related genes, FDA approved drug targets, Biotech drugs, Small molecule drugs

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane; actin filaments; cytosol

Antibody reliability (HPA): IH enhanced · IF supported

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 (2)

Position	Role
1022	proton acceptor
767–768	cleavage; by psen1

Ligand- & substrate-binding residues (2)

Position	Role
833–841	ATP
861	ATP

Post-translational modifications (8)

Type	Positions
Phosphotyrosine	914, 1053, 1169, 1213, 1242, 1309, 1327, 1333

Disulfide bonds (6)

Type	Positions
Disulfide bond	53–107, 158–207, 252–311, 454–535, 577–636, 682–731

Glycosylation sites (13)

Type	Positions
N-linked (glcnac…) asparagine	100, 164, 196, 251, 323, 402, 417, 474, 547, 597, 620, 625, 666

Mutagenesis-validated functional residues (9)

Position	Phenotype
767	abolishes proteolytic cleavage by psen1.
861	abolishes enzyme activity. abolishes interaction with plcg.
914	reduces phosphorylation at other tyrosine residues.
1050	strongly increases kinase activity. increases activity in promoting proliferation of endothelial cells.
1169	loss of phosphorylation site. abolishes interaction with plcg.
1213	loss of phosphorylation site. abolishes interaction with pik3r1.
1242	loss of phosphorylation site.
1327	loss of phosphorylation site.
1333	loss of phosphorylation site. abolishes interaction with cbl.

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 6; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

6 pathways:

ID	Pathway	Evidence
R-HSA-194306	Neuropilin interactions with VEGF and VEGFR	curated
R-HSA-195399	VEGF binds to VEGFR leading to receptor dimerization	curated
R-HSA-162582	Signal Transduction	—
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases	—
R-HSA-194138	Signaling by VEGF	—
R-HSA-194313	VEGF ligand-receptor interactions	—

MSigDB gene sets: 499 (showing top): ATF_B, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, RNGTGGGC_UNKNOWN, MORF_FLT1, GOBP_VASCULAR_ENDOTHELIAL_GROWTH_FACTOR_SIGNALING_PATHWAY, YAGI_AML_WITH_INV_16_TRANSLOCATION, GOBP_MYELOID_LEUKOCYTE_MIGRATION, HARRIS_HYPOXIA, GOBP_CELL_CHEMOTAXIS, GOBP_REGULATION_OF_PHOSPHORYLATION, YAO_HOXA10_TARGETS_VIA_PROGESTERONE_UP, NKX25_02, LFA1_Q6, SP3_Q3, MODULE_64

GO Biological Process (26): sprouting angiogenesis (GO:0002040), monocyte chemotaxis (GO:0002548), 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), cell differentiation (GO:0030154), positive regulation of cell migration (GO:0030335), cellular response to vascular endothelial growth factor stimulus (GO:0035924), vascular endothelial growth factor receptor-1 signaling pathway (GO:0036323), positive regulation of MAP kinase activity (GO:0043406), positive regulation of MAPK cascade (GO:0043410), positive regulation of angiogenesis (GO:0045766), protein autophosphorylation (GO:0046777), vascular endothelial growth factor receptor signaling pathway (GO:0048010), blood vessel morphogenesis (GO:0048514), embryonic morphogenesis (GO:0048598), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), negative regulation of vascular endothelial cell proliferation (GO:1905563), hyaloid vascular plexus regression (GO:1990384), angiogenesis (GO:0001525), protein phosphorylation (GO:0006468), chemotaxis (GO:0006935), vascular endothelial growth factor signaling pathway (GO:0038084), regulation of cell population proliferation (GO:0042127), positive regulation of developmental process (GO:0051094)

GO Molecular Function (12): transmembrane receptor protein tyrosine kinase activity (GO:0004714), vascular endothelial growth factor receptor activity (GO:0005021), ATP binding (GO:0005524), growth factor binding (GO:0019838), placental growth factor receptor activity (GO:0036332), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein tyrosine kinase activity (GO:0004713), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (7): endosome (GO:0005768), plasma membrane (GO:0005886), focal adhesion (GO:0005925), signaling receptor complex (GO:0043235), extracellular region (GO:0005576), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

4 top-level categories:

Category	Pathways
Signaling by VEGF	2
VEGF ligand-receptor interactions	1
Signaling by Receptor Tyrosine Kinases	1
Signal Transduction	1

GO top-level categories

showing 60 of 65 GO namespaces:

Category	Terms
cellular anatomical structure	3
angiogenesis	2
protein phosphorylation	2
positive regulation of intracellular signal transduction	2
transmembrane receptor protein tyrosine kinase activity	2
leukocyte chemotaxis	1
mononuclear cell migration	1
myeloid leukocyte migration	1
enzyme-linked receptor protein signaling pathway	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
cell motility	1
cellular developmental process	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
cellular response to growth factor stimulus	1
vascular endothelial growth factor receptor signaling pathway	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
regulation of angiogenesis	1
positive regulation of vasculature development	1
cell surface receptor protein tyrosine kinase signaling pathway	1
blood vessel development	1
tube morphogenesis	1
anatomical structure morphogenesis	1
embryo development	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
negative regulation of endothelial cell proliferation	1
vascular endothelial cell proliferation	1
regulation of vascular endothelial cell proliferation	1
camera-type eye development	1
anatomical structure regression	1
protein tyrosine kinase activity	1
transmembrane receptor protein 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
vascular endothelial growth factor receptor-1 signaling pathway	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
protein kinase activity	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
cation binding	1
endomembrane system	1
cytoplasmic vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 19 of 46 annotations. The rest are phylogenetic / computational / electronic (IEA).

19 experimentally-supported GO terms:

GO term	NS	Evidence
cell migration	BP	mutant phenotype
cellular response to vascular endothelial growth factor stimulus	BP	direct assay
monocyte chemotaxis	BP	direct assay
negative regulation of vascular endothelial cell proliferation	BP	genetic interaction
peptidyl-tyrosine phosphorylation	BP	direct assay
positive regulation of MAP kinase activity	BP	direct assay
positive regulation of MAPK cascade	BP	direct assay
positive regulation of angiogenesis	BP	mutant phenotype
positive regulation of cell migration	BP	direct assay
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	BP	mutant phenotype
protein autophosphorylation	BP	direct assay
vascular endothelial growth factor receptor signaling pathway	BP	direct assay
vascular endothelial growth factor receptor-1 signaling pathway	BP	direct assay
focal adhesion	CC	high-throughput assay
plasma membrane	CC	direct assay
signaling receptor complex	CC	direct assay
growth factor binding	MF	physical interaction
placental growth factor receptor activity	MF	direct assay
vascular endothelial growth factor receptor activity	MF	direct assay

Protein interactions and networks

IntAct

Human interaction partners of FLT1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

24 partners by confidence:

Partner	Interaction type	MIscore	Records
VEGFA	direct interaction	0.820	7
PTPRJ	dephosphorylation reaction	0.620	2
PGF	direct interaction	0.610	1
PIK3R1	physical association	0.520	3
CRKL	proximity	0.470	9
LDLR	colocalization	0.460	2
CBL	direct interaction	0.440	2
HSPG2	direct interaction	0.440	1
PKM	phosphorylation reaction	0.440	1
SRPK1	phosphorylation reaction	0.440	1
FYN	physical association	0.400	1
LGALS1	physical association	0.400	1
NRP1	physical association	0.400	1
PTPRB	physical association	0.400	1
YES1	physical association	0.400	1
LANCL1	association	0.350	1
CTNNB1	proximity	0.270	2
HCK	proximity	0.270	2
PLCG1	proximity	0.270	2
PTK2	proximity	0.270	2
PTPN11	proximity	0.270	2
CRK	proximity	0.270	1
EEA1	proximity	0.270	1
ILVBL	proximity	0.270	1

BioGRID (206 interactions; top human partners by supporting records): VEGFA (Affinity Capture-MS; 5 records), PIK3R1 (Affinity Capture-Western; 4 records), CRKL (Co-localization; 3 records), PLCG1 (Reconstituted Complex; 3 records), VEGFB (Affinity Capture-Western; 3 records), CALM3 (Affinity Capture-MS; 2 records), CBL (Affinity Capture-Western; 2 records), HSPA1B (Affinity Capture-MS; 2 records), KDR (Affinity Capture-Western; 2 records), MICAL2 (Affinity Capture-Western; 2 records), NEDD4 (Biochemical Activity; 2 records), PTPN11 (Co-localization; 2 records), PWP1 (Proximity Label-MS; 2 records), SHC2 (Two-hybrid; 2 records), ABCF2 (Proximity Label-MS)

SIGNOR signaling

showing 26 of 37 signaling interactions:

A	Effect	B	Mechanism
PTPRJ	down-regulates	FLT1	dephosphorylation
FLT1	up-regulates	FLT1	phosphorylation
VEGFA	up-regulates	FLT1	binding
sunitinib	down-regulates	FLT1	“chemical inhibition”
axitinib	down-regulates	FLT1	“chemical inhibition”
nintedanib	down-regulates	FLT1	“chemical inhibition”
“Brivanib alaninate”	down-regulates	FLT1	“chemical inhibition”
KRN-633	down-regulates	FLT1	“chemical inhibition”
N-[[3-fluoro-4-[[2-(1-methyl-4-imidazolyl)-7-thieno[3,2-b]pyridinyl]oxy]anilino]-sulfanylidenemethyl]-2-phenylacetamide	down-regulates	FLT1	“chemical inhibition”
MK-2461	down-regulates	FLT1	“chemical inhibition”
motesanib	down-regulates	FLT1	“chemical inhibition”
“pazopanib hydrochloride”	down-regulates	FLT1	“chemical inhibition”
PF-03814735	down-regulates	FLT1	“chemical inhibition”
1-[2-chloro-4-[(6,7-dimethoxy-4-quinolinyl)oxy]phenyl]-3-(5-methyl-3-isoxazolyl)urea	down-regulates	FLT1	“chemical inhibition”
vatalanib	down-regulates	FLT1	“chemical inhibition”
pazopanib	“down-regulates activity”	FLT1	“chemical inhibition”
regorafenib	“down-regulates activity”	FLT1	“chemical inhibition”
FLT1	“up-regulates quantity by expression”	PHACTR1	“transcriptional regulation”
FLT1	up-regulates	PLCG1	binding
nintedanib	“down-regulates activity”	FLT1	“chemical inhibition”
motesanib	“down-regulates activity”	FLT1	“chemical inhibition”
5-[(Z)-(5-Fluoro-2-oxo-1H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-3H-pyrrole-3-carboxamide	“down-regulates activity”	FLT1	“chemical inhibition”
“sorafenib tosylate”	“down-regulates activity”	FLT1	“chemical inhibition”
linifanib	“down-regulates activity”	FLT1	“chemical inhibition”
FLT1	“up-regulates activity”	GLO1	phosphorylation
FLT1	“up-regulates activity”	GNAI1	phosphorylation

Protein complexes (CORUM) (14)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

14 complexes by size:

Complex	Subunits	Members
★ FGFR1-FLT1-VEGFB complex	3	FGFR1, FLT1, VEGFB
★ FLT1-ITGB1-KCNH2(isoform B) complex	3	FLT1, ITGB1, KCNH2
★ FLT1-VEGFB167 complex	2	VEGFB, FLT1
★ FLT1-VEGFB186 complex	2	FLT1, VEGFB
★ FLT1-KDR complex	2	FLT1, KDR
★ FLT1-RACK1 complex	2	FLT1, RACK1
★ FLT1-MMP14 complex	2	FLT1, MMP14
★ FLT1-FYN complex	2	FLT1, FYN
★ FLT1-YES complex	2	FLT1, YES1
★ FGFR1-FLT1 complex	2	FGFR1, FLT1
★ FLT1-PLGF-1 complex	2	PGF, FLT1
★ FLT1-VEGFA complex	2	FLT1, VEGFA
★ FLT1-VEGF165B complex	2	FLT1, VEGFA
★ FLT1-VEGF121 complex	2	FLT1, VEGFA

Ligand–receptor pairs (CellPhoneDB) (4)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

4 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
FLT1;KDR		Signaling by Vascular endothelial growth factor
VEGFB	receptor	Signaling by Vascular endothelial growth factor
PGF	receptor	Signaling by Placenta growth factor
VEGFA	receptor	Signaling by Vascular endothelial growth factor

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 24 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	7	158.0×	3e-12
Signaling by CSF1 (M-CSF) in myeloid cells	6	94.4×	4e-09
Downstream signal transduction	5	86.5×	2e-07
Signaling by SCF-KIT	5	56.4×	1e-06
FCGR3A-mediated phagocytosis	5	42.5×	5e-06
VEGFA-VEGFR2 Pathway	5	31.6×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
vascular endothelial growth factor receptor signaling pathway	5	104.7×	6e-07
ephrin receptor signaling pathway	5	74.8×	2e-06
cytokine-mediated signaling pathway	6	34.1×	4e-06
neuron migration	5	29.1×	5e-05
regulation of cell shape	5	26.7×	6e-05
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	6	20.4×	3e-05
angiogenesis	6	16.3×	7e-05
negative regulation of gene expression	5	15.0×	4e-04

Disease & clinical

Genetic variants

Variant evidence for FLT1: 198 ClinVar records (0 pathogenic / likely pathogenic); 18 GWAS associations.

ClinVar

198 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	126
Likely benign	21
Benign	10

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 43 predictions of 2,541):

Position(s)	Effect	Δscore	Sites
13:28306681	donor_gain	1.0000
13:28306773–28306774	acceptor_loss	1.0000	6
13:28308841–28308842	donor_loss	1.0000	6
13:28308928–28308929	acceptor_loss	1.0000	6
13:28311991–28311992	donor_loss	1.0000	5
13:28321461–28321462	donor_loss	1.0000	5
13:28322260–28322261	donor_loss	1.0000	4
13:28322361	acceptor_loss	1.0000	2
13:28322788–28322789	donor_loss	1.0000	3
13:28334023–28334024	donor_loss	1.0000	5

AlphaMissense

2,160 missense substitutions predicted likely pathogenic (of 8,852 scored), across 533 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
M1066	9	0.950	0.996
M1010	9	0.949	0.998
M862	9	0.931	0.993
M1119	9	0.873	0.992
D1040	8	0.999	1.000
D1022	8	0.998	1.000
N1027	8	0.998	1.000
D1081	8	0.996	0.999
H1020	8	0.993	0.998
F1041	8	0.993	0.999
D1046	8	0.975	0.992
F1093	8	0.967	0.995
F838	8	0.966	0.999
H888	8	0.961	0.984
F1147	8	0.956	0.996
N893	8	0.944	0.998
F1109	8	0.938	0.992
N890	8	0.928	0.997
F822	8	0.921	0.998
F1072	8	0.918	0.991

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Kidney Renal Clear Cell Carcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	2.61e-08
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.00039
Ovary Serous Cystadenocarcinoma (validation)	unfavorable	0.000813

Disease associations

OMIM: gene MIM:165070 | disease phenotypes:

HPO phenotypes

27 phenotypes (HPO-id order):

HPO	Term
HP:0000077	Abnormality of the kidney
HP:0000083	Renal insufficiency
HP:0000093	Proteinuria
HP:0000147	Polycystic ovaries
HP:0000504	Abnormality of vision
HP:0000707	Abnormality of the nervous system
HP:0000822	Hypertension
HP:0001511	Intrauterine growth retardation
HP:0001518	Small for gestational age
HP:0001873	Thrombocytopenia
HP:0001919	Acute kidney injury
HP:0002027	Abdominal pain
HP:0002315	Headache
HP:0002360	Sleep disturbance
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0002960	Autoimmunity
HP:0003259	Elevated circulating creatinine concentration
HP:0004421	Elevated systolic blood pressure
HP:0005117	Elevated diastolic blood pressure
HP:0005202	Helicobacter pylori infection
HP:0006707	Abnormality of the hepatic vasculature
HP:0012622	Chronic kidney disease
HP:0031418	Increased body mass index
HP:0100598	Pulmonary edema
HP:0100651	Type I diabetes mellitus
HP:0100767	Abnormal placenta morphology
HP:0410019	Epigastric pain

GWAS associations

18 associations:

Study	Trait	p-value
GCST010867_9	Coronary artery disease	3e-34
GCST010002_233	Refractive error	4e-32
GCST010866_72	Coronary artery disease	5e-20
GCST005196_73	Coronary artery disease	1e-11
GCST90000025_180	Appendicular lean mass	3e-11
GCST005195_79	Coronary artery disease	5e-11
GCST006291_54	Spherical equivalent or myopia (age of diagnosis)	8e-10
GCST005194_41	Coronary artery disease	1e-9
GCST010479_59	Coronary artery disease	3e-9
GCST010244_296	Triglyceride levels	4e-9
GCST010867_64	Coronary artery disease	6e-9
GCST005951_14	Body mass index	2e-8
GCST008362_108	Birth weight	2e-8
GCST010680_1	Acute respiratory distress syndrome in sepsis	5e-8
GCST004787_36	Coronary artery disease (myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, angina or chromic ischemic heart disease)	2e-7
GCST001845_5	Coronary heart disease	6e-7
GCST011365_20	Myocardial infarction	1e-6
GCST000477_49	Cognitive performance	5e-6

EFO canonical traits (from GWAS)

6 canonical traits:

EFO ID	Trait name
EFO:0003926	neuropsychological test
EFO:0004340	body mass index
EFO:0004847	age at onset
EFO:0004344	birth weight
EFO:0004530	triglyceride measurement
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL1868 (SINGLE PROTEIN), CHEMBL2095227 (PROTEIN FAMILY), CHEMBL2111480 (SELECTIVITY GROUP), CHEMBL5482996 (PROTEIN COMPLEX)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the FLT1 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.

5 curated-mechanism drugs:

Drug	Modality	Max phase
SUNITINIB	Small molecule	4
FAMITINIB	Small molecule	3
AEE-788	Small molecule	2
ICRUCUMAB	Antibody	2
TG100-801	Small molecule	2

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes FLT1 — the drug acts on the assembly or class, not necessarily on this subunit alone.

40 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
AXITINIB	Vascular endothelial growth factor receptor	3	4
FRUQUINTINIB	Vascular endothelial growth factor receptor	3	4
LENVATINIB MESYLATE	Vascular endothelial growth factor receptor	3	4
NINTEDANIB ESYLATE	Vascular endothelial growth factor receptor	3	4
PAZOPANIB HYDROCHLORIDE	Vascular endothelial growth factor receptor	3	4
REGORAFENIB	Vascular endothelial growth factor receptor	3	4
SORAFENIB TOSYLATE	Vascular endothelial growth factor receptor	3	4
TIVOZANIB	Vascular endothelial growth factor receptor	3	4
VANDETANIB	Vascular endothelial growth factor receptor	3	4
BRIVANIB	Vascular endothelial growth factor receptor	3	3
BRIVANIB ALANINATE	Vascular endothelial growth factor receptor	3	3
CEDIRANIB	Vascular endothelial growth factor receptor	3	3
DOVITINIB	Vascular endothelial growth factor receptor	3	3
IBCASERTIB	Vascular endothelial growth factor receptor	3	3
LINIFANIB	Vascular endothelial growth factor receptor	3	3
MOTESANIB	Vascular endothelial growth factor receptor	3	3
SEMAXANIB	Vascular endothelial growth factor receptor	3	3
SURUFATINIB	Vascular endothelial growth factor receptor	3	3
VATALANIB	Vascular endothelial growth factor receptor	3	3
AG-13958	Vascular endothelial growth factor receptor	3	2
BMS-690514	Vascular endothelial growth factor receptor	3	2
CEP-11981	Vascular endothelial growth factor receptor	3	2
FORETINIB	Vascular endothelial growth factor receptor	3	2
GLESATINIB	Vascular endothelial growth factor receptor	3	2
ILORASERTIB	Vascular endothelial growth factor receptor	3	2
LUCITANIB	Vascular endothelial growth factor receptor	3	2
SU-014813	Vascular endothelial growth factor receptor	3	2
TELBERMIN	Vascular endothelial growth factor receptor 1 and 2 (Flt-1 and KDR)	2	2
X-82	Vascular endothelial growth factor receptor	3	2
XL-820	Vascular endothelial growth factor receptor	3	2
XL-999	Vascular endothelial growth factor receptor	3	2
4SC-203	Vascular endothelial growth factor receptor	3	1
CEP-5214	Vascular endothelial growth factor receptor	3	1
CEP-7055	Vascular endothelial growth factor receptor	3	1
CP-459632	Vascular endothelial growth factor receptor	3	1
KRN-633	Vascular endothelial growth factor receptor	3	1
L-21649	Vascular endothelial growth factor receptor	3	1
OSI-930	Vascular endothelial growth factor receptor	3	1
RG-1530	Vascular endothelial growth factor receptor	3	1
TAK-593	Vascular endothelial growth factor receptor	3	1

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 308,845 (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 77 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL535	SUNITINIB	4	80,232
CHEMBL1289926	AXITINIB	4	16,510
CHEMBL2105717	CABOZANTINIB	4	11,799
CHEMBL601719	CRIZOTINIB	4	15,133
CHEMBL5416410	DASATINIB	4	674
CHEMBL1983268	ENTRECTINIB	4	3,737
CHEMBL553	ERLOTINIB	4	109,860
CHEMBL1287853	FEDRATINIB	4	3,770
CHEMBL3301607	FILGOTINIB	4	3,101
CHEMBL4303214	FRUQUINTINIB	4	793
CHEMBL1852688	INFIGRATINIB	4	2,298
CHEMBL1834657	INFIGRATINIB PHOSPHATE	4	330
CHEMBL1289601	LENVATINIB	4	9,224
CHEMBL608533	MIDOSTAURIN	4	7,641
CHEMBL502835	NINTEDANIB	4	8,978
CHEMBL3039504	NINTEDANIB ESYLATE	4	691
CHEMBL477772	PAZOPANIB	4	16,241
CHEMBL3813873	PEXIDARTINIB	4	3,751
CHEMBL1171837	PONATINIB	4	9,435
CHEMBL576982	QUIZARTINIB	4	4,647
CHEMBL1946170	REGORAFENIB	4
CHEMBL1336	SORAFENIB	4
CHEMBL1289494	TIVOZANIB	4
CHEMBL3646221	VADADUSTAT	4
CHEMBL24828	VANDETANIB	4
CHEMBL483158	ALISERTIB	3
CHEMBL377300	BRIVANIB	3
CHEMBL31965	CANERTINIB	3
CHEMBL491473	CEDIRANIB	3
CHEMBL290352	CEP-1347	3
CHEMBL3137331	DEFACTINIB	3
CHEMBL522892	DOVITINIB	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL223360	LINIFANIB	3
CHEMBL572881	MOTESANIB	3
CHEMBL274654	ORANTINIB	3
CHEMBL276711	SEMAXANIB	3
CHEMBL4297190	SURUFATINIB	3
CHEMBL3544983	TESEVATINIB	3
CHEMBL101253	VATALANIB	3
CHEMBL587723	AEE-788	2
CHEMBL495727	AT-9283	2
CHEMBL4080062	BFH-772	2
CHEMBL1967878	CENISERTIB	2
CHEMBL2010872	CEP-11981	2
CHEMBL2029988	CEP-32496	2
CHEMBL215152	DEFOSBARASERTIB	2
CHEMBL103667	DORAMAPIMOD	2
CHEMBL1230609	FORETINIB	2
CHEMBL1980297	ILORASERTIB	2
CHEMBL2220486	LUCITANIB	2
CHEMBL1822792	MK-2461	2
CHEMBL253969	OSI-632	2
CHEMBL1938400	PF-03715455	2
CHEMBL475251	R-406	2
CHEMBL558752	RAF-265	2
CHEMBL1738757	REBASTINIB	2
CHEMBL1721885	SU-014813	2
CHEMBL124660	TANDUTINIB	2
CHEMBL572878	TOZASERTIB	2

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

9 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs664393	sorafenib	Efficacy	Genotype TT is associated with decreased overall survival and progression-free survival when treated with sorafenib in people with Carcinoma, Hepatocellular as compared to genotypes CC + CT.	PMID:24510746
rs9582036	sunitinib	Efficacy	Genotype CC is associated with decreased overall survival and progression-free survival when treated with sunitinib in people with Carcinoma, Renal Cell as compared to genotypes AA + AC.	PMID:27417418
rs7993418	sunitinib	Efficacy	Genotype GG is associated with decreased overall survival when treated with sunitinib in people with Carcinoma, Renal Cell as compared to genotypes AA + AG.	PMID:27417418
rs9554320	sunitinib	Efficacy	Genotype AA is associated with decreased overall survival and progression-free survival when treated with sunitinib in people with Carcinoma, Renal Cell as compared to genotypes AC + CC.	PMID:27417418
rs9582036	sunitinib	Efficacy	Genotype CC is associated with decreased overall survival and progression-free survival when treated with sunitinib in people with Carcinoma, Renal Cell as compared to genotypes AA + AC.	PMID:23421954
rs9554320	sunitinib	Efficacy	Genotype AA is associated with decreased overall survival and progression-free survival when treated with sunitinib in people with Carcinoma, Renal Cell as compared to genotypes AC + CC.	PMID:23421954
rs9582036	sunitinib	Efficacy	Genotype CC is associated with decreased overall survival when treated with sunitinib in people with Carcinoma, Renal Cell as compared to genotypes AA + AC.	PMID:26935927
rs966	imatinib	Toxicity	Genotype AA is associated with increased likelihood of Myelosuppression when treated with imatinib in people with Gastrointestinal Stromal Tumors as compared to genotypes AC + CC.	PMID:41193444
rs9551465	imatinib	Toxicity	Genotype CC is associated with decreased likelihood of Myelosuppression when treated with imatinib in people with Gastrointestinal Stromal Tumors as compared to genotypes AA + AC.	PMID:41193444

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: catalytic receptor — Type IV RTKs: VEGF (vascular endothelial growth factor) receptor family

Most potent curated ligand interactions (32 total), top 25:

Ligand	Action	Affinity	Parameter
tivozanib	Inhibition	9.68	pIC50
foretinib	Inhibition	9.1	pIC50
VEGF receptor tyrosine kinase inhibitor III	Inhibition	9.0	pIC50
ilorasertib	Inhibition	9.0	pIC50
motesanib	Inhibition	8.7	pIC50
SU-14813	Inhibition	8.7	pIC50
tinengotinib	Inhibition	8.62	pIC50
linifanib	Inhibition	8.52	pIC50
dovitinib	Inhibition	8.52	pIC50
CEP-11981	Inhibition	8.52	pIC50
catequentinib	Inhibition	8.4	pIC50
cediranib	Inhibition	8.3	pIC50
sitravatinib	Inhibition	8.22	pIC50
compound 8h [PMID: 22765894]	Inhibition	8.14	pIC50
ibcasertib	Inhibition	8.1	pIC50
semaxanib	Inhibition	8.1	pIC50
OSI-930	Inhibition	8.1	pIC50
RG-1530	Inhibition	8.05	pKd
pazopanib	Inhibition	8.0	pIC50
MK-2461	Inhibition	8.0	pIC50
dorsomorphin	Inhibition	7.96	pIC50
lucitanib	Inhibition	7.92	pIC50
compound 8i [PMID: 22765894]	Inhibition	7.54	pIC50
nintedanib	Inhibition	7.51	pIC50
Cdk1/2 inhibitor III	Inhibition	7.49	pIC50

Binding affinities (BindingDB)

1275 measured of 1709 human assays (1711 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
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
CHEMBL3939307	IC50	0.1 nM
CHEMBL6150730	IC50	0.18 nM
CHEMBL4163870	IC50	0.19 nM
CHEMBL6162898	IC50	0.22 nM
CHEMBL6114929	IC50	0.28 nM
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
CHEMBL5407330	IC50	0.73 nM
CHEMBL5410108	IC50	0.76 nM
CHEMBL5412144	IC50	0.86 nM
CHEMBL5403470	IC50	0.88 nM
CHEMBL5394759	IC50	0.98 nM
CHEMBL5421802	IC50	0.99 nM
Jak Inhibitor 1	EC50	1 nM
(1H-Indol-5-yl)-(6-thiophen-2-yl-thieno[3,2-d]pyrimidin-4-yl)-amine	IC50	1 nM
2-{4-[4-(1H-Indol-5-ylamino)-thieno[3,2-d]pyrimidin-6-yl]-benzylamino}-2-methyl-propan-1-ol	IC50	1 nM
(1H-Indol-5-yl)-(2-thiophen-2-yl-thieno[3,2-b]pyridin-7-yl)-amine	IC50	1 nM
N*4*-(1H-Indol-5-yl)-N*6*-(2-phenylamino-ethyl)-N*6*-pyrrol-1-yl-thieno[3,2-d]pyrimidine-4,6-diamine	IC50	1 nM
{4-[4-(1H-Indol-5-ylamino)-thieno[3,2-d]pyrimidin-6-yl]-phenyl}-methanol	IC50	1 nM
1-{4-[7-(1H-Indol-5-ylamino)-thieno[3,2-b]pyridin-2-yl]-benzyl}-isonicotinamide	IC50	1 nM
CHEMBL3764474	IC50	1 nM
CHEMBL5393865	IC50	1 nM
CHEMBL5438830	IC50	1.1 nM
CHEMBL5411585	IC50	1.4 nM
REGORAFENIB	IC50	1.5 nM
CHEMBL6146585	IC50	1.6 nM
Staurosporine	KD	1.7 nM
6-[[2-[[4-[4-(2-hydroxyethyl)piperazin-1-yl]benzoyl]amino]-4-pyridinyl]oxy]-N-methylnaphthalene-1-carboxamide	IC50	1.8 nM	US-11834432: Substituted amino six-membered nitric heterocyclic ring compound and preparation and use thereof
CHEMBL3765306	IC50	1.9 nM
5-[4-[4-[(3-methylphenyl)carbamoylamino]phenoxy]-2-pyridinyl]-1H-pyrrole-3-carboxylic acid	IC50	2 nM	US-8614234: Compounds as tyrosine kinase modulators
N-(2-{4-[7-(1H-Indol-5-ylamino)-thieno[3,2-b]pyridin-2-yl]-benzylamino}-ethyl)-acetamide	IC50	2 nM
2-{4-[7-(1H-Indol-5-ylamino)-thieno[3,2-b]pyridin-2-yl]-benzylamino}-ethanol	IC50	2 nM
5-(4-(piperidin-1-yl)piperidin-1-yl)-2-(6-(trifluoromethyl)-1H-indazol-3-yl)-1H-benzo[d]imidazole	IC50	2 nM
(3S,5Z,8S,9R,11E)-8,9,16-trihydroxy-14-methoxy-3-methyl-3,4,9,10-tetrahydro-1H-benzo[c][1]oxacyclotetradecine-1,7(8H)-dione	IC50	2 nM
CHEMBL404367	IC50	2 nM
CHEMBL6103505	IC50	2 nM
CHEMBL4160854	IC50	2.1 nM
CHEMBL5421149	IC50	2.1 nM
5-((5-(4-((4-(2-hydroxyethyl)piperazin-1-yl)methyl)-3-(trifluoromethyl)phenylcarbamoyl)-2-methylphenyl)ethynyl)-N,1-dimethyl-1H-imidazole-2-carboxamide	IC50	2.2 nM
CHEMBL5410264	IC50	2.2 nM
CHEMBL6173446	IC50	2.3 nM
CHEMBL4463714	IC50	2.4 nM
CHEMBL5408069	IC50	2.5 nM
CHEMBL3357439	IC50	2.7 nM
FIIN-1	KD	2.8 nM
CHEMBL5436823	IC50	2.9 nM
CHEMBL5403747	IC50	2.9 nM
4-[[5-[4-[3-fluoro-4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]-2-pyridinyl]-1H-pyrrole-3-carbonyl]amino]butanoic acid	IC50	3 nM	US-8614234: Compounds as tyrosine kinase modulators
5-[4-[3-fluoro-4-[(3-methylphenyl)carbamoylamino]phenoxy]-2-pyridinyl]-1H-pyrrole-3-carboxylic acid	IC50	3 nM	US-8614234: Compounds as tyrosine kinase modulators
methyl 5-[4-[3-fluoro-4-[(3-methylphenyl)carbamoylamino]phenoxy]-2-pyridinyl]-1H-pyrrole-3-carboxylate	IC50	3 nM	US-9725433: Compounds as tyrosine kinase modulators

ChEMBL bioactivities

1886 potent at pChembl≥5 of 2051 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.30	Ki	0.05012	nM	CHEMBL272938
10.20	Ki	0.0631	nM	CHEMBL1986979
10.10	Ki	0.07943	nM	CHEMBL374044
10.00	IC50	0.1	nM	CHEMBL3939307
10.00	IC50	0.1	nM	AXITINIB
10.00	Ki	0.1	nM	CHEMBL1993996
9.90	Ki	0.1259	nM	CHEMBL1994638
9.80	Ki	0.1585	nM	CHEMBL373798
9.80	Ki	0.1585	nM	CHEMBL271441
9.70	Ki	0.1995	nM	CHEMBL1967116
9.70	Ki	0.1995	nM	CHEMBL403402
9.68	IC50	0.21	nM	TIVOZANIB
9.60	Ki	0.2512	nM	CHEMBL1974254
9.60	Ki	0.2512	nM	CHEMBL1996255
9.60	Ki	0.2512	nM	CHEMBL2000335
9.60	Ki	0.2512	nM	CHEMBL1978601
9.60	Ki	0.2512	nM	CHEMBL1969102
9.60	Ki	0.2512	nM	CHEMBL409349
9.50	Ki	0.3162	nM	CHEMBL1980904
9.50	Ki	0.3162	nM	CHEMBL1985888
9.50	Ki	0.3162	nM	CHEMBL2005631
9.40	Ki	0.3981	nM	CHEMBL1993941
9.40	Ki	0.3981	nM	CHEMBL1989708
9.40	Ki	0.3981	nM	CHEMBL2004716
9.40	Ki	0.3981	nM	CHEMBL1965988
9.40	Ki	0.3981	nM	CHEMBL1988717
9.40	Ki	0.3981	nM	CHEMBL2002446
9.40	Ki	0.3981	nM	CHEMBL272453
9.30	IC50	0.5	nM	CHEMBL429743
9.30	Ki	0.5012	nM	CHEMBL1970142
9.30	Ki	0.5012	nM	CHEMBL2002165
9.30	Ki	0.5012	nM	CHEMBL1988387
9.30	Ki	0.5012	nM	CHEMBL1983963
9.30	Ki	0.5012	nM	CHEMBL387971
9.20	Ki	0.631	nM	CHEMBL1980407
9.20	Ki	0.631	nM	CHEMBL1973178
9.20	Ki	0.631	nM	CHEMBL2000652
9.20	Ki	0.631	nM	CHEMBL2006778
9.20	Ki	0.631	nM	CHEMBL411903
9.20	Ki	0.631	nM	CHEMBL220057
9.20	Ki	0.631	nM	CHEMBL1982466
9.16	Ki	0.697	nM	2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN
9.14	IC50	0.73	nM	CHEMBL5407330
9.13	Kd	0.74	nM	CEDIRANIB
9.12	IC50	0.76	nM	CHEMBL5410108
9.10	IC50	0.8	nM	FORETINIB
9.10	Ki	0.7943	nM	CHEMBL1994321
9.10	Ki	0.7943	nM	CHEMBL1973211
9.10	Ki	0.7943	nM	CHEMBL1964692
9.10	Ki	0.7943	nM	CHEMBL1979883

PubChem BioAssay actives

1336 with measured affinity, of 4220 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
N-methyl-2-[[3-(2-pyridin-2-ylethyl)-2H-indazol-6-yl]sulfanyl]benzamide	1331762: Inhibition of VEGFR1 (unknown origin)	ic50	0.0001	uM
Axitinib	1424498: Inhibition of VEGFR1 (unknown origin)	ic50	0.0001	uM
Tivozanib	710633: Inhibition of VEGFR1	ic50	0.0002	uM
N-(4-chlorophenyl)-6-(6,7-dimethoxyquinolin-4-yl)oxynaphthalene-1-carboxamide	326938: Inhibition of VEGFR1	ic50	0.0005	uM
1-[2-chloro-4-[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]oxyphenyl]-3-[4-(trifluoromethoxy)phenyl]urea	1975502: Inhibition of VEGFR1 (unknown origin)	ic50	0.0007	uM
4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline	624853: Binding constant for FLT1 kinase domain	kd	0.0007	uM
1-[2-chloro-4-[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]oxyphenyl]-3-(1-methylindol-5-yl)urea	1975502: Inhibition of VEGFR1 (unknown origin)	ic50	0.0008	uM
1-N’-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	710633: Inhibition of VEGFR1	ic50	0.0008	uM
1-[2-chloro-4-[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]oxyphenyl]-3-(1-propan-2-ylpyrazol-4-yl)urea	1975502: Inhibition of VEGFR1 (unknown origin)	ic50	0.0009	uM
1-[2-chloro-4-[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]oxyphenyl]-3-(3-fluoro-4-methylphenyl)urea	1975502: Inhibition of VEGFR1 (unknown origin)	ic50	0.0009	uM
1-tert-butyl-3-[3-[6-(4-piperidin-1-ylpiperidin-1-yl)-1H-benzimidazol-2-yl]-1H-indazol-5-yl]urea	268026: Inhibition of VEGFR1	ic50	0.0010	uM
4-fluoro-2-[5-[[(1R)-2-hydroxy-1-phenylethyl]amino]-3-(3-methyl-2H-indazol-5-yl)-2-pyridinyl]phenol	1450715: Inhibition of recombinant VEGFR-1 (unknown origin) using poly (Glu,Tyr) 4:1 as substrate after 60 mins by ELISA	ic50	0.0010	uM
1-[2-chloro-4-[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]oxyphenyl]-3-(1-cyclopentylpyrazol-4-yl)urea	1975502: Inhibition of VEGFR1 (unknown origin)	ic50	0.0010	uM
1-[2-chloro-4-[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]oxyphenyl]-3-[3-(trifluoromethyl)phenyl]urea	1975502: Inhibition of VEGFR1 (unknown origin)	ic50	0.0010	uM
1-[2-chloro-4-[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]oxyphenyl]-3-(2-fluoro-5-methylphenyl)urea	1975502: Inhibition of VEGFR1 (unknown origin)	ic50	0.0010	uM
N-[2-(dimethylamino)ethyl]-1-[3-[[4-[(2-methyl-1H-indol-5-yl)oxy]pyrimidin-2-yl]amino]phenyl]methanesulfonamide	2131259: Inhibition of VEGFR1 (unknown origin)	ic50	0.0010	uM
Sunitinib	684153: Inhibition of N-terminal GST-tagged Flt1 using poly(Glu,Tyr) as substrate after 60 mins by alphascreen assay	ic50	0.0010	uM
1-[2-chloro-4-(6,7-dimethoxyquinazolin-4-yl)oxyphenyl]-3-propylurea	325648: Inhibition of human VEGFR1 in HUVEC cells	ic50	0.0010	uM
2,4-difluoro-N-methoxy-5-[[6-(5-methyl-1,3-oxazol-2-yl)-5-propan-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-yl]amino]benzamide	248164: Inhibition of VEGF-stimulated human umbilical vein endothelial cell proliferation	ic50	0.0011	uM
1-[2-chloro-4-[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]oxyphenyl]-3-(5-methyl-1,2-oxazol-3-yl)urea	1975502: Inhibition of VEGFR1 (unknown origin)	ic50	0.0011	uM
(7Z)-N-[2-(diethylamino)ethyl]-7-(5-fluoro-2-oxo-1H-indol-3-ylidene)-2-methyl-1,4,5,6-tetrahydroindole-3-carboxamide	773008: Inhibition of VEGFR1 (unknown origin)	ic50	0.0013	uM
1-[2-chloro-4-[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]oxyphenyl]-3-[4-(trifluoromethyl)phenyl]urea	1975502: Inhibition of VEGFR1 (unknown origin)	ic50	0.0014	uM
regorafenib anhydrous	1600255: Inhibition of VEGFR1 (unknown origin)	ic50	0.0015	uM
N-(3-tert-butyl-1,2-oxazol-5-yl)-2-[4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]phenyl]acetamide	2214729: Inhibition of FLT1 (unknown origin)	ic50	0.0016	uM
2-[4-[5-(1-methylpyrazol-4-yl)benzimidazol-1-yl]phenyl]-N-(3-propan-2-yl-1,2-oxazol-5-yl)acetamide	2214729: Inhibition of FLT1 (unknown origin)	ic50	0.0016	uM
5-[[6-(5-ethyl-1,3,4-oxadiazol-2-yl)-5-propan-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-yl]amino]-2,4-difluoro-N-methoxybenzamide	248164: Inhibition of VEGF-stimulated human umbilical vein endothelial cell proliferation	ic50	0.0018	uM
N-(3,3-dimethyl-1,2-dihydroindol-6-yl)-2-(pyridin-4-ylmethylamino)pyridine-3-carboxamide	1304585: Inhibition of VEGFR1 (unknown origin)	ic50	0.0020	uM
3-[6-(4-piperidin-1-ylpiperidin-1-yl)-1H-benzimidazol-2-yl]-6-(trifluoromethyl)-1H-indazole	268026: Inhibition of VEGFR1	ic50	0.0020	uM
2-[4-[1-[4-[2-[(3-tert-butyl-1,2-oxazol-5-yl)amino]-2-oxoethyl]phenyl]benzimidazol-5-yl]pyrazol-1-yl]acetic acid	2214729: Inhibition of FLT1 (unknown origin)	ic50	0.0020	uM
N-(3-tert-butyl-1,2-oxazol-5-yl)-2-[4-[5-(1H-pyrazol-4-yl)benzimidazol-1-yl]phenyl]acetamide	2214729: Inhibition of FLT1 (unknown origin)	ic50	0.0020	uM
6-[(4-methylpiperazin-1-yl)methyl]-3-[5-(3-phenoxyprop-1-ynyl)thiophen-3-yl]-1,4-dihydroindeno[2,1-d]pyrazole	286520: Inhibition of Flt1	ic50	0.0020	uM
1-[[4-[4-(1H-indol-5-ylamino)thieno[3,2-d]pyrimidin-6-yl]phenyl]methyl]piperidine-4-carboxamide	216625: Inhibitory activity against Vascular endothelial growth factor receptor	ic50	0.0020	uM
4-[6-[4-(2-morpholin-4-ylethoxy)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]benzene-1,2-diol	527866: Inhibition of FLT1 by Hot Spot filtration binding assay	ic50	0.0020	uM
2-chloro-4-fluoro-5-[[6-methoxy-7-(2-methoxyethoxy)quinazolin-4-yl]amino]phenol	1795652: VEGF-R Kinase Inhibition Assay from Article 10.1021/jm990345w: “Design and structure-activity relationship of a new class of potent VEGF receptor tyrosine kinase inhibitors.”	ic50	0.0020	uM
N-[4-[2-(3-tert-butylanilino)-1-methylbenzimidazol-5-yl]oxy-2-pyridinyl]acetamide	1255117: Inhibition of VEGFR (unknown origin)	ic50	0.0020	uM
1-[4-(4-aminothieno[2,3-d]pyrimidin-5-yl)phenyl]-3-(3-methylphenyl)urea	255092: Inhibitory concentration against FLT1 with 4 uM Biotin-Ahx-AEEEYFFLFA-amide for 1 hr at ambient temperature	ic50	0.0020	uM
Lenvatinib	2231223: Inhibition of VEGFR1 (unknown origin)	ic50	0.0020	uM
2,4-difluoro-N-methoxy-5-[[6-[5-(methylsulfonylmethyl)-1,3,4-oxadiazol-2-yl]-5-propan-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-yl]amino]benzamide	248164: Inhibition of VEGF-stimulated human umbilical vein endothelial cell proliferation	ic50	0.0021	uM
2,4-difluoro-N-methoxy-5-[[6-[5-(2-methylpropyl)-1,3,4-oxadiazol-2-yl]-5-propan-2-ylpyrrolo[2,1-f][1,2,4]triazin-4-yl]amino]benzamide	248164: Inhibition of VEGF-stimulated human umbilical vein endothelial cell proliferation	ic50	0.0021	uM
1-[2-fluoro-4-[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]oxyphenyl]-3-(1-propan-2-ylpyrazol-4-yl)urea	1975502: Inhibition of VEGFR1 (unknown origin)	ic50	0.0021	uM
1-[2-chloro-4-[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]oxyphenyl]-3-(4-methylphenyl)urea	1975502: Inhibition of VEGFR1 (unknown origin)	ic50	0.0022	uM
1-benzyl-3-[2-chloro-4-[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]oxyphenyl]urea	1975502: Inhibition of VEGFR1 (unknown origin)	ic50	0.0025	uM
1-(1-benzofuran-5-yl)-3-[2-chloro-4-[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]oxyphenyl]urea	1975502: Inhibition of VEGFR1 (unknown origin)	ic50	0.0029	uM
1-butyl-3-[2-chloro-4-[6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-yl]oxyphenyl]urea	1975502: Inhibition of VEGFR1 (unknown origin)	ic50	0.0029	uM
1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methylphenyl)urea	1388692: Inhibition of FLT1 (unknown origin)	ic50	0.0030	uM
3-[5-[3-(2-methoxyethoxy)prop-1-ynyl]thiophen-3-yl]-7-(1,2,4-triazol-1-ylmethyl)-1,4-dihydroindeno[2,1-d]pyrazole	286520: Inhibition of Flt1	ic50	0.0030	uM
19-methyl-3-(2-methylpropyl)-7-(pyrimidin-2-ylamino)-3,13,19,20-tetrazahexacyclo[14.7.0.02,10.04,9.011,15.017,21]tricosa-1(16),2(10),4(9),5,7,11(15),17,20-octaen-14-one	653721: Inhibition of human VEGFR1 using ATP as substrate	ic50	0.0030	uM
N-[[3-fluoro-4-[2-(1-methylimidazol-2-yl)thieno[2,3-b]pyridin-4-yl]oxyphenyl]carbamothioyl]-2-phenylacetamide	1276926: Inhibition of VEGFR-1 (unknown origin) by tumor cell growth inhibition assay	ic50	0.0030	uM
4-amino-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-1,7-naphthyridin-2-one	263661: Inhibitory activity against VEGFR1	ic50	0.0030	uM
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one	411863: Inhibition of VEGFR1	ic50	0.0030	uM

CTD chemical–gene interactions

137 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, increases methylation	8
trichostatin A	affects cotreatment, increases expression	4
bisphenol A	affects cotreatment, increases methylation, decreases expression, increases expression	3
Resveratrol	decreases reaction, increases expression, increases secretion, decreases expression, decreases secretion	3
Benzo(a)pyrene	increases expression, increases methylation, affects methylation	3
Cadmium	decreases reaction, increases expression, decreases expression, increases activity	3
Oxygen	decreases reaction, increases expression, affects reaction	3
sodium arsenite	affects localization, affects reaction, decreases expression	2
cobaltous chloride	decreases expression, increases expression, decreases reaction	2
mercuric bromide	increases expression, affects cotreatment	2
perfluorooctane sulfonic acid	affects expression, affects secretion, decreases activity	2
entinostat	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	2
belinostat	increases expression, affects cotreatment	2
ponatinib	decreases activity	2
Vorinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Acetylcysteine	decreases reaction, increases expression	2
Ascorbic Acid	affects binding, affects cotreatment, decreases expression	2
Cannabidiol	affects cotreatment, increases expression	2
Glucose	affects cotreatment, decreases expression, decreases reaction	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tetradecanoylphorbol Acetate	increases expression, increases reaction, decreases reaction, increases secretion	2
Dronabinol	affects cotreatment, increases expression, decreases reaction	2
Tobacco Smoke Pollution	decreases expression, increases methylation	2
cornin iridoid	decreases response to substance, decreases reaction, increases expression	1
GSK2656157	increases splicing	1
ODN2006	increases secretion	1
4-methylumbelliferone 8-carbaldehyde	decreases reaction, increases splicing	1

ChEMBL screening assays

896 unique, capped per target: 852 binding, 38 functional, 6 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000443	Binding	Inhibition of human VEGFR1 expressed in baculovirus insect cell system	Mixed-lineage kinase 1 and mixed-lineage kinase 3 subtype-selective dihydronaphthyl[3,4-a]pyrrolo[3,4-c]carbazole-5-ones: optimization, mixed-lineage kinase 1 crystallography, and oral in vivo activity in 1-methyl-4-phenyltetrahydropyridine models. — *J Med Chem*
CHEMBL1963826	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: FLT1	PubChem BioAssay data set
CHEMBL4002770	ADMET	Inhibition of recombinant VEGFR1 (unknown origin) using poly (Glu,Tyr) 4:1 as substrate after 60 mins by ELISA	Discovery of novel Ponatinib analogues for reducing KDR activity as potent FGFRs inhibitors. — *Eur J Med Chem*

Cellosaurus cell lines

7 cell lines: 6 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B8G3	Abcam HCT 116 FLT1 KO	Cancer cell line	Male
CVCL_B8VX	Abcam MCF-7 FLT1 KO	Cancer cell line	Female
CVCL_B9IB	Abcam A-549 FLT1 KO	Cancer cell line	Male
CVCL_D1SF	Abcam U-87MG FLT1 KO	Cancer cell line	Male
CVCL_D9EY	Ubigene HEK293 FLT1 KO	Transformed cell line	Female
CVCL_SN74	HAP1 FLT1 (-) 1	Cancer cell line	Male
CVCL_SN75	HAP1 FLT1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT01169220	Phase 4	COMPLETED	Bowel Preparation for Inpatient Colonoscopy
NCT01170754	Phase 4	COMPLETED	Miralax (PEG 3350) vs. Golytely as Bowel Preparation for Screening Colonoscopy
NCT02052557	Phase 4	COMPLETED	The Effect of Exparel on Post Operative Pain and Narcotic Use After Colon Surgery
NCT02078726	Phase 4	COMPLETED	Glucagon Use in Colonoscopies
NCT02231203	Phase 4	COMPLETED	Effect of Omega-3 Fatty Acids on the Perioperative Immune Response and Erythrocyte Function
NCT02314871	Phase 4	COMPLETED	Effects of Different Types of Perioperative Analgesia on Minimal Residual Disease Development After Colon Cancer Surgery
NCT02746432	Phase 4	UNKNOWN	Insulin Therapy Reduce Post-Operative Inflammatory Response After Curative Colorectal Cancer Resection: Randomization Controlled Trial
NCT02887365	Phase 4	UNKNOWN	A Phase II Study of Tegafur-Uracil as Maintenance Chemotherapy in Patients With Stage II of Colon Cancer
NCT02937506	Phase 4	COMPLETED	Patient Satisfaction With Propofol for Out Patient Colonoscopy
NCT02958566	Phase 4	UNKNOWN	Multimodal Narcotic Limited Perioperative Pain Control With Colorectal Surgery
NCT04269369	Phase 4	UNKNOWN	Implementation of Pre-emptive Geno- and Phenotyping in 5-Fluorouracil- or Capecitabine-treated Patients
NCT04311099	Phase 4	COMPLETED	Optimal Peripheral Nerve Block After Minimally Invasive Colon Surgery
NCT04709770	Phase 4	UNKNOWN	Low-volume vs High-volume Polyethylene Glycol Based Bowel Preparation for Colonoscopy in People Receiving Hemodialysis
NCT05250648	Phase 4	RECRUITING	Clinical Trial on HIPEC With Mitomycin C in Colon Cancer Peritoneal Metastases (GECOP-MMC)
NCT07802847	Phase 4	NOT_YET_RECRUITING	Innovative and Cooperative Pathway Integrating Oncogeriatric, Pharmaceutical and Pharmacological Follow-up in Elderly Patients.
NCT00002968	Phase 3	COMPLETED	Edrecolomab in Treating Patients With Stage II Colon Cancer
NCT00003835	Phase 3	COMPLETED	Combination Chemotherapy in Treating Patients With Stage III Colon Cancer
NCT00003873	Phase 3	COMPLETED	Fluorouracil With or Without Eniluracil in Treating Patients With Advanced Colorectal Cancer
NCT00004931	Phase 3	COMPLETED	Fluorouracil Plus Leucovorin With or Without Oxaliplatin in Treating Patients With Stage II or Stage III Colon Cancer
NCT00005036	Phase 3	COMPLETED	Irinotecan Compared With Combination Chemotherapy in Treating Patients With Advanced Colorectal Cancer
NCT00005094	Phase 3	COMPLETED	Celecoxib to Prevent Colorectal Cancer in Patients Who Have Undergone Surgery to Remove Polyps
NCT00025337	Phase 3	COMPLETED	Combination Chemotherapy With or Without Bevacizumab Compared With Bevacizumab Alone in Treating Patients With Advanced or Metastatic Colorectal Cancer That Has Been Previously Treated
NCT00070122	Phase 3	TERMINATED	Combination Chemotherapy and Bevacizumab in Treating Patients With Locally Advanced, Metastatic, or Recurrent Colorectal Cancer
NCT00079274	Phase 3	COMPLETED	Comparison of Combination Chemotherapy Regimens With or Without Cetuximab in Treating Patients Who Have Undergone Surgery For Stage III Colon Cancer
NCT00096278	Phase 3	COMPLETED	Fluorouracil, Leucovorin, and Oxaliplatin With or Without Bevacizumab in Treating Patients Who Have Undergone Surgery for Stage II or Stage III Colon Cancer
NCT00188305	Phase 3	COMPLETED	A Randomized Trial of Cancer Risk and Health Education in Relatives of Colorectal Cancer Patients
NCT00195585	Phase 3	COMPLETED	Study Evaluating Isovorin in Colon Cancer
NCT00217737	Phase 3	COMPLETED	Oxaliplatin, Leucovorin, and Fluorouracil With or Without Bevacizumab in Treating Patients Who Have Undergone Surgery for Stage II Colon Cancer
NCT00230646	Phase 3	COMPLETED	Promoting Physical Activity After Colorectal Cancer
NCT00309530	Phase 3	COMPLETED	Randomized Study on Adjuvant Chemotherapy and Adjuvant Chemo-Immunotherapy in Colon Carcinoma Dukes C
NCT00309543	Phase 3	COMPLETED	Randomized Trial on Adjuvant Chemotherapy in Colon Carcinoma Dukes B
NCT00337389	Phase 3	UNKNOWN	Phase III Randomized Study of 5-FU, CoFactor, and Avastin vs. 5-FU, LV and Avastin for First-Line Colorectal Cancer.
NCT00467922	Phase 3	COMPLETED	An Assessment of Goal-Directed Intraoperative Fluid Management in Hand Assisted Laparoscopic Colectomy
NCT00499369	Phase 3	TERMINATED	Irinotecan and Cetuximab With or Without Bevacizumab in Treating Patients With Metastatic Colorectal Cancer That Progressed During First-Line Therapy
NCT00509444	Phase 3	COMPLETED	Cancer Prevention and Treatment Among African American Older Adults: Treatment Trial
NCT00646607	Phase 3	COMPLETED	FOLFOX-4 3months Versus 6 Months and Bevacizumab as Adjuvant Therapy for Patients With Stage II/III Colon Cancer
NCT00687830	Phase 3	COMPLETED	Efficacy of Morning-only Bowel Preparation for Afternoon Colonoscopy.
NCT00756548	Phase 3	COMPLETED	BLI850-302: BLI850 vs an Approved Active Control Bowel Preparation in Adult Subjects Undergoing Colonoscopy
NCT00756977	Phase 3	COMPLETED	BLI850 vs an Active Control Bowel Preparation in Adult Subjects Undergoing Colonoscopy
NCT00894725	Phase 3	COMPLETED	Laparoscopic Versus Open Left Colonic Resection
NCT00911170	Phase 3	COMPLETED	PAVES: Pegfilgrastim Anti-vascular Endothelial Growth Factor (VEGF) Evaluation Study
NCT01092481	Phase 3	UNKNOWN	Study Investigating the Role of Oxaliplatin Duration in Modified FOLFOX-6 or CAPOX Regimen as Adjuvant Colon Cancer Therapy
NCT01460589	Phase 3	ACTIVE_NOT_RECRUITING	Early Commencement of Adjuvant Chemotherapy for Colon Cancer
NCT01483443	Phase 3	COMPLETED	Oophorectomy Followed by Chemotherapy Versus Chemotherapy Alone in Colorectal Cancer Patients
NCT01606098	Phase 3	COMPLETED	The Role of Surgery of the Primary Tumour in Patients With Synchronous Unresectable Metastases of Colorectal Cancer
NCT01727388	Phase 3	COMPLETED	Informativeness to Digital Rectal Examination
NCT01918527	Phase 3	COMPLETED	Neoadjuvant Chemotherapy Versus Standard Treatment in Patients With Locally Advanced Colon Cancer
NCT02254486	Phase 3	COMPLETED	Multicenter Randomized Parallel Group Phase III Study Comparing the Bowel Cleansing Efficacy, Safety and Tolerability of NER1006 Versus Trisulfate Solution Using 2-Day Split-Dosing Regimen in Adults
NCT02280278	Phase 3	UNKNOWN	Cytokine-induced Killer Cell Immunotherapy for Surgical Resected Stage III Colorectal Cancer Patients After Chemotherapy
NCT02301286	Phase 3	ACTIVE_NOT_RECRUITING	A Trial of Aspirin on Recurrence and Survival in Colon Cancer Patients
NCT02448173	Phase 3	NOT_YET_RECRUITING	A Multicenter Study of Active Specific Immunotherapy With OncoVax® in Patients With Stage II Colon Cancer
NCT02467582	Phase 3	TERMINATED	Adjuvant Aspirin Treatment for Colon Cancer Patients
NCT02519140	Phase 3	WITHDRAWN	Assessing How the Viscosity of Submucosal Gel Injections Helps With Endoscopic Mucosal Resections
NCT02572141	Phase 3	ACTIVE_NOT_RECRUITING	FOLFOX or CAPOX Perioperative Chemotherapy Versus Postoperative Chemotherapy for Locally Advanced Colon Cancer (OPTICAL)
NCT02588248	Phase 3	TERMINATED	L-Menthol Injection as a Novel Technique During Colonoscopy
NCT02682589	Phase 3	UNKNOWN	Open Versus Laparoscopic Complete Mesocolic Excision for Locally Advanced Colon Cancer
NCT02912052	Phase 3	UNKNOWN	Perioperative Chemotherapy VS Postoperative Chemotherapy for the Treatment of Colon Cancer With Resectable Liver Metastasis
NCT02912559	Phase 3	ACTIVE_NOT_RECRUITING	Combination Chemotherapy With or Without Atezolizumab in Treating Patients With Stage III Colon Cancer and Deficient DNA Mismatch Repair
NCT02928692	Phase 3	UNKNOWN	Minocycline Attenuate Postoperative Cognitive Dysfunction and Delirium
NCT02967289	Phase 3	COMPLETED	IRinotecan and Oxaliplatin for Colon Cancer in Adjuvant Setting

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for FLT1 across ~30M SureChEMBL compounds — explore on Sugi Predict.