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): 196 total
• Phenotypes (HPO): 27
• Druggable target: yes — 77 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002019

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: 14 — 8 protein_coding, 5 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

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

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.

FANTOM5 promoters (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

294 total, 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

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

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)

119 targeting FLT1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

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

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)

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): P17948, A0A1W2PNW4, 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), 1 shown:

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)

UniProt features (124 total): strand 20, helix 19, 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.

PDB	Method	Resolution (Å)
1FLT	X-RAY DIFFRACTION	1.7
5ABD	X-RAY DIFFRACTION	2
4CL7	X-RAY DIFFRACTION	2
4CKV	X-RAY DIFFRACTION	2.06
5EX3	X-RAY DIFFRACTION	2.41
1RV6	X-RAY DIFFRACTION	2.45
1QTY	X-RAY DIFFRACTION	2.7
3HNG	X-RAY DIFFRACTION	2.7
2XAC	X-RAY DIFFRACTION	2.71
5T89	X-RAY DIFFRACTION	4
1QSV	SOLUTION NMR
1QSZ	SOLUTION NMR

Predicted structure (AlphaFold)

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

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): 1022 (proton acceptor); 767–768 (cleavage; by psen1)

Ligand- & substrate-binding residues (2): 833–841; 861

Post-translational modifications (8): 914, 1053, 1169, 1213, 1242, 1309, 1327, 1333

Disulfide bonds (6): 53–107, 158–207, 252–311, 454–535, 577–636, 682–731

Glycosylation sites (13): 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 pathways

ID	Pathway
R-HSA-194306	Neuropilin interactions with VEGF and VEGFR
R-HSA-195399	VEGF binds to VEGFR leading to receptor dimerization

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 (10): obsolete extracellular space (GO:0005615), endosome (GO:0005768), cytosol (GO:0005829), plasma membrane (GO:0005886), focal adhesion (GO:0005925), actin cytoskeleton (GO:0015629), signaling receptor complex (GO:0043235), extracellular region (GO:0005576), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by VEGF	1
VEGF ligand-receptor interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
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
peptidyl-tyrosine modification	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 interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

59 interactions, top by confidence:

A	B	Type	Score
VEGFA	FLT1	psi-mi:“MI:0407”(direct interaction)	0.820
FLT1	VEGFA	psi-mi:“MI:0407”(direct interaction)	0.820
VEGFA	FLT1	psi-mi:“MI:0915”(physical association)	0.820
FLT1	VEGFA	psi-mi:“MI:0915”(physical association)	0.820
VEGFA	VEGFA	psi-mi:“MI:0915”(physical association)	0.670
PTPRJ	FLT1	psi-mi:“MI:0203”(dephosphorylation reaction)	0.620
FLT1	PTPRJ	psi-mi:“MI:0203”(dephosphorylation reaction)	0.620
FLT1	PGF	psi-mi:“MI:0407”(direct interaction)	0.610
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
PIK3R1	FLT1	psi-mi:“MI:0915”(physical association)	0.520
PIK3R1	FLT1	psi-mi:“MI:2364”(proximity)	0.520
FLT1	VEGFA	psi-mi:“MI:0915”(physical association)	0.520
VEGFA	FLT1	psi-mi:“MI:0915”(physical association)	0.520
FLT1	CRKL	psi-mi:“MI:2364”(proximity)	0.470
CRKL	FLT1	psi-mi:“MI:2364”(proximity)	0.470
CRKL	FLT1	psi-mi:“MI:0915”(physical association)	0.470
FLT1	LDLR	psi-mi:“MI:0403”(colocalization)	0.460
FLT1	LDLR	psi-mi:“MI:0915”(physical association)	0.460
FLT1	SRPK1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
FLT1	HSPG2	psi-mi:“MI:0407”(direct interaction)	0.440
FLT1	CBL	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (202): CBL (Affinity Capture-Western), KDR (Affinity Capture-Western), SHC1 (Two-hybrid), PTPN11 (Co-localization), PIK3R1 (Affinity Capture-Western), FLT1 (Affinity Capture-Western), SHC2 (Two-hybrid), FLT1 (Affinity Capture-MS), FLT1 (Affinity Capture-MS), FLT1 (Protein-peptide), FLT1 (Two-hybrid), FLT1 (Biochemical Activity), KDR (Biochemical Activity), FLT1 (Affinity Capture-Western), MICAL2 (Affinity Capture-Western)

ESM2 similar proteins: A0A0R4IGV4, A0A8M2B818, A0JM41, A2VD98, B0CLX4, B6ZK77, D3YX43, F1LW30, O00241, O18906, O54901, O88775, O95256, P00545, P04218, P0C673, P10522, P13369, P17948, P21995, P27931, P35916, P35917, P35969, P37301, P42071, P42703, P53767, Q08DK1, Q15762, Q58EG3, Q5DX21, Q5FWR8, Q5R412, Q5U2P2, Q5VJ70, Q6GMZ9, Q6PCB8, Q6X936, Q7TSN7

Diamond homologs: D2IYS2, G3V9H8, O08775, O42127, O73791, O73798, O97799, P00529, P00545, P04048, P05532, P05622, P07333, P07949, P09581, P09619, P10721, P11362, P13369, P16092, P16234, P17948, P18460, P18461, P20786, P21802, P21803, P21804, P22182, P22455, P22607, P23049, P26618, P26619, P33497, P35546, P35590, P35916, P35917, P35918

SIGNOR signaling

37 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”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 40 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	112.1×	5e-11
Signaling by CSF1 (M-CSF) in myeloid cells	6	67.0×	5e-08
Downstream signal transduction	5	61.4×	2e-06
Signaling by SCF-KIT	5	40.0×	9e-06
FCGR3A-mediated phagocytosis	5	30.2×	3e-05
VEGFA-VEGFR2 Pathway	6	27.0×	6e-06

GO biological processes:

GO term	Partners	Fold	FDR
vascular endothelial growth factor receptor signaling pathway	5	68.8×	7e-06
ephrin receptor signaling pathway	5	49.1×	2e-05
integrin-mediated signaling pathway	5	22.9×	2e-04
cytokine-mediated signaling pathway	6	22.4×	3e-05
regulation of cell shape	6	21.1×	3e-05
neuron migration	5	19.1×	3e-04
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	7	15.7×	3e-05
positive regulation of ERK1 and ERK2 cascade	5	12.2×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	125
Likely benign	20
Benign	10

Top pathogenic / likely-pathogenic (0)

SpliceAI

4876 predictions. Top by Δscore:

Variant	Effect	Δscore
13:28303369:C:CC	acceptor_gain	1.0000
13:28306676:A:AC	donor_gain	1.0000
13:28306677:C:CT	donor_gain	1.0000
13:28306677:CT:C	donor_gain	1.0000
13:28306680:A:AC	donor_gain	1.0000
13:28306680:AAT:A	donor_gain	1.0000
13:28306681:A:C	donor_gain	1.0000
13:28306770:GTC:G	acceptor_gain	1.0000
13:28306771:TC:T	acceptor_gain	1.0000
13:28306772:CC:C	acceptor_gain	1.0000
13:28306773:C:CC	acceptor_gain	1.0000
13:28306773:C:G	acceptor_loss	1.0000
13:28308837:ACTTA:A	donor_loss	1.0000
13:28308838:CT:C	donor_loss	1.0000
13:28308839:TTAC:T	donor_loss	1.0000
13:28308841:A:AC	donor_gain	1.0000
13:28308841:A:AT	donor_loss	1.0000
13:28308842:C:CC	donor_gain	1.0000
13:28308842:CAT:C	donor_gain	1.0000
13:28308923:CGTAT:C	acceptor_gain	1.0000
13:28308924:GTAT:G	acceptor_gain	1.0000
13:28308925:TAT:T	acceptor_gain	1.0000
13:28308926:AT:A	acceptor_gain	1.0000
13:28308926:ATCTA:A	acceptor_loss	1.0000
13:28308927:TCTA:T	acceptor_loss	1.0000
13:28308928:C:CC	acceptor_gain	1.0000
13:28308929:T:G	acceptor_loss	1.0000
13:28311991:A:C	donor_loss	1.0000
13:28311992:C:CA	donor_loss	1.0000
13:28321457:A:AC	donor_gain	1.0000

AlphaMissense

8852 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
13:28319462:A:G	W1083R	1.000
13:28319462:A:T	W1083R	1.000
13:28319514:C:A	W1065C	1.000
13:28319514:C:G	W1065C	1.000
13:28319516:A:G	W1065R	1.000
13:28319516:A:T	W1065R	1.000
13:28321513:C:G	G1042R	1.000
13:28321518:T:A	D1040V	1.000
13:28321518:T:C	D1040G	1.000
13:28321518:T:G	D1040A	1.000
13:28321519:C:G	D1040H	1.000
13:28321556:G:C	N1027K	1.000
13:28321556:G:T	N1027K	1.000
13:28321560:C:A	R1026I	1.000
13:28321572:T:A	D1022V	1.000
13:28321572:T:G	D1022A	1.000
13:28322304:A:C	S1003R	1.000
13:28322304:A:T	S1003R	1.000
13:28322306:T:G	S1003R	1.000
13:28329635:C:T	G896E	1.000
13:28329636:C:G	G896R	1.000
13:28329636:C:T	G896R	1.000
13:28329686:A:G	L879P	1.000
13:28329698:A:G	L875P	1.000
13:28334035:T:A	K861N	1.000
13:28334035:T:G	K861N	1.000
13:28339198:A:G	W820R	1.000
13:28339198:A:T	W820R	1.000
13:28312076:A:G	W1137R	0.999
13:28312076:A:T	W1137R	0.999

dbSNP variants (sampled 300 via entrez): RS1000001345 (13:28427048 C>T), RS1000005110 (13:28404623 A>G), RS1000034133 (13:28324460 A>C), RS1000051082 (13:28484332 G>T), RS1000086148 (13:28317629 T>A), RS1000104756 (13:28411726 G>A), RS1000124323 (13:28336028 A>G,T), RS1000151021 (13:28495324 G>A,C,T), RS1000157928 (13:28454266 T>C), RS1000211865 (13:28441232 G>A), RS1000214943 (13:28308498 C>A,T), RS1000233379 (13:28430376 C>A,T), RS1000249288 (13:28436859 T>C), RS1000279159 (13:28342178 C>T), RS1000282637 (13:28418084 C>T)

Disease associations

OMIM: gene MIM:165070 | disease phenotypes:

GenCC curated gene-disease

Mondo (3): colon carcinoma (MONDO:0002032), lung adenocarcinoma (MONDO:0005061), squamous cell carcinoma (MONDO:0005096)

Orphanet (1): NON RARE IN EUROPE: Adenocarcinoma of the lung (Orphanet:415268)

HPO phenotypes

27 total (27 of 27 shown, 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 (top):

Study	Trait	p-value
GCST000477_49	Cognitive performance	5.000000e-06
GCST001845_5	Coronary heart disease	6.000000e-07
GCST004787_56	Coronary artery disease (myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, angina or chromic ischemic heart disease)	2.000000e-07
GCST005194_126	Coronary artery disease	1.000000e-09
GCST005195_120	Coronary artery disease	5.000000e-11
GCST005196_73	Coronary artery disease	1.000000e-11
GCST005951_4	Body mass index	2.000000e-08
GCST006291_79	Spherical equivalent or myopia (age of diagnosis)	8.000000e-10
GCST008362_50	Birth weight	2.000000e-08
GCST010002_181	Refractive error	4.000000e-32
GCST010244_98	Triglyceride levels	4.000000e-09
GCST010479_32	Coronary artery disease	3.000000e-09
GCST010680_1	Acute respiratory distress syndrome in sepsis	5.000000e-08
GCST010866_101	Coronary artery disease	5.000000e-20
GCST010867_39	Coronary artery disease	6.000000e-09
GCST010867_9	Coronary artery disease	3.000000e-34
GCST011365_145	Myocardial infarction	1.000000e-06
GCST90000025_1039	Appendicular lean mass	3.000000e-11

EFO canonical traits (6, from GWAS)

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

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D002294	Carcinoma, Squamous Cell	C04.557.470.200.400; C04.557.470.700.400

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)

Molecules with ChEMBL bioactivity

77 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 311,149 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1171837	PONATINIB	4	8,955
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289494	TIVOZANIB	4	4,455
CHEMBL1289601	LENVATINIB	4	8,784
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1834657	INFIGRATINIB PHOSPHATE	4	285
CHEMBL1852688	INFIGRATINIB	4	2,209
CHEMBL1946170	REGORAFENIB	4	12,678
CHEMBL1983268	ENTRECTINIB	4	3,510
CHEMBL2105717	CABOZANTINIB	4	11,177
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL3039504	NINTEDANIB ESYLATE	4	659
CHEMBL3301607	FILGOTINIB	4	2,905
CHEMBL3646221	VADADUSTAT	4	533
CHEMBL3813873	PEXIDARTINIB	4	3,586
CHEMBL4303214	FRUQUINTINIB	4	732
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL5416410	DASATINIB	4
CHEMBL553	ERLOTINIB	4
CHEMBL576982	QUIZARTINIB	4
CHEMBL601719	CRIZOTINIB	4
CHEMBL608533	MIDOSTAURIN	4
CHEMBL101253	VATALANIB	3
CHEMBL223360	LINIFANIB	3
CHEMBL274654	ORANTINIB	3
CHEMBL276711	SEMAXANIB	3
CHEMBL290352	CEP-1347	3

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

8 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs664393	FLT1		0.00	0
rs7993418	FLT1		0.00	0
rs7995976	FLT1		0.00	0
rs12877323	FLT1		0.00	0
rs9582036	FLT1		0.00	0
rs9554320	FLT1		0.00	0
rs966	FLT1		0.00	0
rs9551465	FLT1		0.00	0

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)

305 measured of 391 human assays (391 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Staurosporine	KD	1.7 nM
FORETINIB	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
FIIN-1	KD	2.8 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
FRIN-1	KD	3.1 nM
N-(2-fluoro-3,5-dimethoxyphenyl)-N-(1H-imidazol-2-ylmethyl)-7-(1-methylpyrazol-4-yl)pteridin-2-amine	IC50	3.16 nM	US-10272087: Pteridines as FGFR inhibitors
1-[5-[4-[3-fluoro-4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]-2-pyridinyl]-1H-pyrrole-3-carbonyl]pyrrolidine-3-carboxylic acid	IC50	4 nM	US-8614234: Compounds as tyrosine kinase modulators
4-[[5-[4-[4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]-2-pyridinyl]-1H-pyrrole-3-carbonyl]amino]butanoic acid	IC50	4 nM	US-8614234: Compounds as tyrosine kinase modulators
5-[4-[4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]-2-pyridinyl]-1H-pyrrole-3-carboxylic acid	IC50	4 nM	US-8614234: Compounds as tyrosine kinase modulators
3-[[5-[4-[3-fluoro-4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]-2-pyridinyl]-1H-pyrrole-3-carbonyl]amino]propanoic acid	IC50	5 nM	US-8614234: Compounds as tyrosine kinase modulators
1-[5-[4-[4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]-2-pyridinyl]-1H-pyrrole-3-carbonyl]pyrrolidine-3-carboxylic acid	IC50	5 nM	US-8614234: Compounds as tyrosine kinase modulators
N-ethyl-5-[4-[4-[(3-methylphenyl)carbamoylamino]phenoxy]-2-pyridinyl]-1H-pyrrole-3-carboxamide	IC50	5 nM	US-8614234: Compounds as tyrosine kinase modulators
1-[4-[[2-[4-[(3R)-3-hydroxypiperidine-1-carbonyl]-1H-pyrrol-2-yl]-4-pyridinyl]oxy]phenyl]-3-(3-methylphenyl)urea	IC50	6 nM	US-8614234: Compounds as tyrosine kinase modulators
7-[3-fluoro-4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]-N-(3-morpholin-4-ylpropyl)thieno[3,2-b]pyridine-2-carboxamide	IC50	7 nM	US-9340555: Compounds as tyrosine kinase modulators
4-[[7-[3-fluoro-4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]thieno[3,2-b]pyridine-2-carbonyl]amino]butanoic acid	IC50	7 nM	US-9340555: Compounds as tyrosine kinase modulators
4-[[7-[4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]thieno[3,2-b]pyridine-2-carbonyl]amino]butanoic acid	IC50	7 nM	US-9340555: Compounds as tyrosine kinase modulators
7-[3-fluoro-4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]-N-[3-[3-(hydroxymethyl)piperidin-1-yl]propyl]thieno[3,2-b]pyridine-2-carboxamide	IC50	8 nM	US-9340555: Compounds as tyrosine kinase modulators
7-[3-fluoro-4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]-N-[3-(4-hydroxypiperidin-1-yl)propyl]thieno[3,2-b]pyridine-2-carboxamide	IC50	8 nM	US-9340555: Compounds as tyrosine kinase modulators
methyl (2S,4R)-1-[3-[[7-[3-fluoro-4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]thieno[3,2-b]pyridine-2-carbonyl]amino]propyl]-4-hydroxypyrrolidine-2-carboxylate	IC50	8 nM	US-9340555: Compounds as tyrosine kinase modulators
7-[3-fluoro-4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]-N-[3-[2-(hydroxymethyl)morpholin-4-yl]propyl]thieno[3,2-b]pyridine-2-carboxamide	IC50	9 nM	US-9340555: Compounds as tyrosine kinase modulators
7-[4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]-N-[3-(4-methylpiperazin-1-yl)propyl]thieno[3,2-b]pyridine-2-carboxamide	IC50	9 nM	US-9340555: Compounds as tyrosine kinase modulators
BMS-907351	IC50	9.9 nM
5-[4-[4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]-2-pyridinyl]-N-(3-hydroxypropyl)-1H-pyrrole-3-carboxamide	IC50	10 nM	US-8614234: Compounds as tyrosine kinase modulators
3-[4-[(3-methylphenyl)carbamoylamino]phenyl]-5-(3-morpholin-4-ylpropylcarbamoylamino)-1,2-thiazole-4-carboxamide	IC50	10 nM	US-8969583: 3-phenyl-5-ureidoisothiazole-4-carboximide and 3-amino-5-phenylisothiazole derivatives as kinase inhibitors
7-[4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]-N-[2-(2H-tetrazol-5-yl)ethyl]thieno[3,2-b]pyridine-2-carboxamide	IC50	10 nM	US-9340555: Compounds as tyrosine kinase modulators
7-[4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]-N-[3-[3-(hydroxymethyl)piperidin-1-yl]propyl]thieno[3,2-b]pyridine-2-carboxamide	IC50	10 nM	US-9340555: Compounds as tyrosine kinase modulators
7-[4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]-N-[3-[2-(hydroxymethyl)morpholin-4-yl]propyl]thieno[3,2-b]pyridine-2-carboxamide	IC50	10 nM	US-9340555: Compounds as tyrosine kinase modulators
methyl (2S,4R)-1-[3-[[7-[4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]thieno[3,2-b]pyridine-2-carbonyl]amino]propyl]-4-hydroxypyrrolidine-2-carboxylate	IC50	10 nM	US-9340555: Compounds as tyrosine kinase modulators
methyl 2-[3-[[7-[3-fluoro-4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]thieno[3,2-b]pyridine-2-carbonyl]amino]propyl-(2-methoxy-2-oxoethyl)amino]acetate	IC50	10 nM	US-9340555: Compounds as tyrosine kinase modulators
ethyl 2-[4-[2-[4-[7-[3-fluoro-4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]thieno[3,2-b]pyridine-2-carbonyl]piperazin-1-yl]acetyl]piperazin-1-yl]acetate	IC50	10 nM	US-9340555: Compounds as tyrosine kinase modulators
N-[3-[2-[4-amino-1-(4-hydroxycyclohexyl)pyrazolo[3,4-d]pyrimidin-3-yl]ethynyl]-4-methylphenyl]-4-methyl-3-(trifluoromethyl)benzamide	IC50	10 nM	US-10266537: 3-acetylenyl-pyrazole-pyrimidine derivative, and preparation method therefor and uses thereof
3-[(4-bromo-2,6-difluorophenyl)methoxy]-5-({[4-(pyrrolidin-1-yl)butyl]carbamoyl}amino)-1,2-thiazole-4-carboxamide	IC50	10.1 nM	US-9446026: Ocular formulations for drug-delivery to the posterior segment of the eye
methyl 2-[3-[[7-[4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]thieno[3,2-b]pyridine-2-carbonyl]amino]propylamino]acetate	IC50	11 nM	US-9340555: Compounds as tyrosine kinase modulators
methyl 2-[3-[[7-[3-fluoro-4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]thieno[3,2-b]pyridine-2-carbonyl]amino]propylamino]acetate	IC50	11 nM	US-9340555: Compounds as tyrosine kinase modulators
methyl 2-[2-[[7-[3-fluoro-4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]thieno[3,2-b]pyridine-2-carbonyl]amino]ethyl-(2-methoxy-2-oxoethyl)amino]acetate	IC50	11 nM	US-9340555: Compounds as tyrosine kinase modulators
N-(2-aminoethyl)-7-[3-fluoro-4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]thieno[3,2-b]pyridine-2-carboxamide	IC50	11 nM	US-9340555: Compounds as tyrosine kinase modulators
7-[3-fluoro-4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]-N-[3-(4-methylpiperazin-1-yl)propyl]thieno[3,2-b]pyridine-2-carboxamide	IC50	11 nM	US-9340555: Compounds as tyrosine kinase modulators
3-[4-[(4-methylphenyl)carbamoylamino]phenyl]-5-(3-morpholin-4-ylpropylcarbamoylamino)-1,2-thiazole-4-carboxamide	IC50	12 nM	US-8969583: 3-phenyl-5-ureidoisothiazole-4-carboximide and 3-amino-5-phenylisothiazole derivatives as kinase inhibitors
N-[3-(diethylamino)propyl]-7-[4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]thieno[3,2-b]pyridine-2-carboxamide	IC50	12 nM	US-9340555: Compounds as tyrosine kinase modulators
5-[4-[3-[(3-methylphenyl)carbamoyl]phenoxy]-2-pyridinyl]-1H-pyrrole-3-carboxylic acid	IC50	13 nM	US-8614234: Compounds as tyrosine kinase modulators
5-[4-[4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]-2-pyridinyl]-N-hydroxy-1H-pyrrole-3-carboxamide	IC50	13 nM	US-8614234: Compounds as tyrosine kinase modulators
ethyl 2-[4-[3-[[7-[4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]thieno[3,2-b]pyridine-2-carbonyl]amino]propyl]piperazin-1-yl]acetate	IC50	13 nM	US-9340555: Compounds as tyrosine kinase modulators
ethyl 4-[2-[[7-[3-fluoro-4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]thieno[3,2-b]pyridine-2-carbonyl]amino]ethyl]piperazine-1-carboxylate	IC50	13 nM	US-9340555: Compounds as tyrosine kinase modulators
methyl 2-[2-[[7-[3-fluoro-4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]thieno[3,2-b]pyridine-2-carbonyl]amino]ethylamino]acetate	IC50	13 nM	US-9340555: Compounds as tyrosine kinase modulators
N-[2-(diethylamino)ethyl]-7-[4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]thieno[3,2-b]pyridine-2-carboxamide	IC50	13 nM	US-9340555: Compounds as tyrosine kinase modulators
methyl 2-[3-[[7-[4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]thieno[3,2-b]pyridine-2-carbonyl]amino]propyl-(2-methoxy-2-oxoethyl)amino]acetate	IC50	14 nM	US-9340555: Compounds as tyrosine kinase modulators
ethyl 4-[3-[[7-[3-fluoro-4-[(2-fluoro-5-methylphenyl)carbamoylamino]phenoxy]thieno[3,2-b]pyridine-2-carbonyl]amino]propyl]piperazine-1-carboxylate	IC50	14 nM	US-9340555: 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

1317 with measured affinity, of 4191 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
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
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
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
2-(5-phenylmethoxy-1H-indazol-3-yl)-6-(4-piperidin-1-ylpiperidin-1-yl)-1H-benzimidazole	268026: Inhibition of VEGFR1	ic50	0.0030	uM
(E)-N-[4-[4-amino-3-(3,5-dimethyl-1-benzofuran-2-yl)-7-oxo-6H-pyrazolo[3,4-d]pyridazin-2-yl]phenyl]-4-(dimethylamino)but-2-enamide	2131507: Inhibition of VEGFR1 (unknown origin)	ic50	0.0030	uM
2-[methyl-[[4-[7-[(2-methyl-1H-indol-5-yl)amino]thieno[3,2-b]pyridin-2-yl]phenyl]methyl]amino]ethanol	216625: Inhibitory activity against Vascular endothelial growth factor receptor	ic50	0.0030	uM
N-(2-methyl-1H-indol-5-yl)-2-[4-[(2-piperazin-1-ylethylamino)methyl]phenyl]thieno[3,2-b]pyridin-7-amine	216625: Inhibitory activity against Vascular endothelial growth factor receptor	ic50	0.0030	uM
2-[[4-[4-(1H-indol-5-ylamino)thieno[3,2-d]pyrimidin-6-yl]phenyl]methylamino]-2-methylpropan-1-ol	216625: Inhibitory activity against Vascular endothelial growth factor receptor	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	increases expression, affects cotreatment, increases methylation, decreases expression	3
Resveratrol	increases secretion, decreases expression, decreases secretion, decreases reaction, increases expression	3
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	3
Cadmium	decreases reaction, increases expression, decreases expression, increases activity	3
Oxygen	decreases reaction, increases expression, affects reaction	3
sodium arsenite	affects reaction, decreases expression, affects localization	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	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Acetylcysteine	increases expression, decreases reaction	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 reaction, increases expression, decreases response to substance	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)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT01169220	PHASE4	COMPLETED	Bowel Preparation for Inpatient Colonoscopy
NCT01170754	PHASE4	COMPLETED	Miralax (PEG 3350) vs. Golytely as Bowel Preparation for Screening Colonoscopy
NCT02052557	PHASE4	COMPLETED	The Effect of Exparel on Post Operative Pain and Narcotic Use After Colon Surgery
NCT02078726	PHASE4	COMPLETED	Glucagon Use in Colonoscopies
NCT02231203	PHASE4	COMPLETED	Effect of Omega-3 Fatty Acids on the Perioperative Immune Response and Erythrocyte Function
NCT02314871	PHASE4	COMPLETED	Effects of Different Types of Perioperative Analgesia on Minimal Residual Disease Development After Colon Cancer Surgery
NCT02746432	PHASE4	UNKNOWN	Insulin Therapy Reduce Post-Operative Inflammatory Response After Curative Colorectal Cancer Resection: Randomization Controlled Trial
NCT02887365	PHASE4	UNKNOWN	A Phase II Study of Tegafur-Uracil as Maintenance Chemotherapy in Patients With Stage II of Colon Cancer
NCT02937506	PHASE4	COMPLETED	Patient Satisfaction With Propofol for Out Patient Colonoscopy
NCT02958566	PHASE4	UNKNOWN	Multimodal Narcotic Limited Perioperative Pain Control With Colorectal Surgery
NCT04269369	PHASE4	UNKNOWN	Implementation of Pre-emptive Geno- and Phenotyping in 5-Fluorouracil- or Capecitabine-treated Patients
NCT04311099	PHASE4	COMPLETED	Optimal Peripheral Nerve Block After Minimally Invasive Colon Surgery
NCT04709770	PHASE4	UNKNOWN	Low-volume vs High-volume Polyethylene Glycol Based Bowel Preparation for Colonoscopy in People Receiving Hemodialysis
NCT05250648	PHASE4	RECRUITING	Clinical Trial on HIPEC With Mitomycin C in Colon Cancer Peritoneal Metastases (GECOP-MMC)
NCT00002968	PHASE3	COMPLETED	Edrecolomab in Treating Patients With Stage II Colon Cancer
NCT00003835	PHASE3	COMPLETED	Combination Chemotherapy in Treating Patients With Stage III Colon Cancer
NCT00003873	PHASE3	COMPLETED	Fluorouracil With or Without Eniluracil in Treating Patients With Advanced Colorectal Cancer
NCT00004931	PHASE3	COMPLETED	Fluorouracil Plus Leucovorin With or Without Oxaliplatin in Treating Patients With Stage II or Stage III Colon Cancer
NCT00005036	PHASE3	COMPLETED	Irinotecan Compared With Combination Chemotherapy in Treating Patients With Advanced Colorectal Cancer
NCT00005094	PHASE3	COMPLETED	Celecoxib to Prevent Colorectal Cancer in Patients Who Have Undergone Surgery to Remove Polyps
NCT00025337	PHASE3	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	PHASE3	TERMINATED	Combination Chemotherapy and Bevacizumab in Treating Patients With Locally Advanced, Metastatic, or Recurrent Colorectal Cancer
NCT00079274	PHASE3	COMPLETED	Comparison of Combination Chemotherapy Regimens With or Without Cetuximab in Treating Patients Who Have Undergone Surgery For Stage III Colon Cancer
NCT00096278	PHASE3	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	PHASE3	COMPLETED	A Randomized Trial of Cancer Risk and Health Education in Relatives of Colorectal Cancer Patients
NCT00195585	PHASE3	COMPLETED	Study Evaluating Isovorin in Colon Cancer
NCT00217737	PHASE3	ACTIVE_NOT_RECRUITING	Oxaliplatin, Leucovorin, and Fluorouracil With or Without Bevacizumab in Treating Patients Who Have Undergone Surgery for Stage II Colon Cancer
NCT00230646	PHASE3	COMPLETED	Promoting Physical Activity After Colorectal Cancer
NCT00309530	PHASE3	COMPLETED	Randomized Study on Adjuvant Chemotherapy and Adjuvant Chemo-Immunotherapy in Colon Carcinoma Dukes C
NCT00309543	PHASE3	COMPLETED	Randomized Trial on Adjuvant Chemotherapy in Colon Carcinoma Dukes B
NCT00337389	PHASE3	UNKNOWN	Phase III Randomized Study of 5-FU, CoFactor, and Avastin vs. 5-FU, LV and Avastin for First-Line Colorectal Cancer.
NCT00467922	PHASE3	COMPLETED	An Assessment of Goal-Directed Intraoperative Fluid Management in Hand Assisted Laparoscopic Colectomy
NCT00499369	PHASE3	TERMINATED	Irinotecan and Cetuximab With or Without Bevacizumab in Treating Patients With Metastatic Colorectal Cancer That Progressed During First-Line Therapy
NCT00509444	PHASE3	COMPLETED	Cancer Prevention and Treatment Among African American Older Adults: Treatment Trial
NCT00646607	PHASE3	COMPLETED	FOLFOX-4 3months Versus 6 Months and Bevacizumab as Adjuvant Therapy for Patients With Stage II/III Colon Cancer
NCT00687830	PHASE3	COMPLETED	Efficacy of Morning-only Bowel Preparation for Afternoon Colonoscopy.
NCT00756548	PHASE3	COMPLETED	BLI850-302: BLI850 vs an Approved Active Control Bowel Preparation in Adult Subjects Undergoing Colonoscopy
NCT00756977	PHASE3	COMPLETED	BLI850 vs an Active Control Bowel Preparation in Adult Subjects Undergoing Colonoscopy
NCT00894725	PHASE3	COMPLETED	Laparoscopic Versus Open Left Colonic Resection
NCT00911170	PHASE3	COMPLETED	PAVES: Pegfilgrastim Anti-vascular Endothelial Growth Factor (VEGF) Evaluation Study