ITGAV

Summary

ITGAV (integrin subunit alpha V, HGNC:6150) is a protein-coding gene on chromosome 2q32.1, encoding Integrin alpha-V (P06756). The alpha-V (ITGAV) integrins are receptors for vitronectin, cytotactin, fibronectin, fibrinogen, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin and vWF. It is a selective cancer dependency (DepMap: 44.1% of cell lines).

The product of this gene belongs to the integrin alpha chain family. Integrins are heterodimeric integral membrane proteins composed of an alpha subunit and a beta subunit that function in cell surface adhesion and signaling. The encoded preproprotein is proteolytically processed to generate light and heavy chains that comprise the alpha V subunit. This subunit associates with beta 1, beta 3, beta 5, beta 6 and beta 8 subunits. The heterodimer consisting of alpha V and beta 3 subunits is also known as the vitronectin receptor. This integrin may regulate angiogenesis and cancer progression. Alternative splicing results in multiple transcript variants. Note that the integrin alpha 5 and integrin alpha V subunits are encoded by distinct genes.

Source: NCBI Gene 3685 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 205 total — 3 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 39
• Druggable target: yes — 8 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• Cancer dependency (DepMap): dependent in 44.1% of screened cell lines
• MANE Select transcript: NM_002210

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6150
Approved symbol	ITGAV
Name	integrin subunit alpha V
Location	2q32.1
Locus type	gene with protein product
Status	Approved
Aliases	CD51
Ensembl gene	ENSG00000138448
Ensembl biotype	protein_coding
OMIM	193210
Entrez	3685

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 15 protein_coding, 9 retained_intron, 3 nonsense_mediated_decay

ENST00000261023, ENST00000374907, ENST00000430709, ENST00000433736, ENST00000460641, ENST00000496477, ENST00000496854, ENST00000696906, ENST00000696907, ENST00000696908, ENST00000696909, ENST00000696910, ENST00000696911, ENST00000696912, ENST00000696913, ENST00000696914, ENST00000696915, ENST00000696916, ENST00000696917, ENST00000696918, ENST00000696919, ENST00000696936, ENST00000696937, ENST00000877363, ENST00000925191, ENST00000925192, ENST00000925193

RefSeq mRNA: 3 — MANE Select: NM_002210 NM_001144999, NM_001145000, NM_002210

CCDS: CCDS2292, CCDS46470, CCDS46471

Canonical transcript exons

ENST00000261023 — 30 exons

Exon	Start	End
ENSE00000783598	186649840	186649885
ENSE00000783599	186651982	186652089
ENSE00000783600	186654650	186654708
ENSE00000783601	186656247	186656401
ENSE00000783608	186667671	186667776
ENSE00000783611	186675604	186675717
ENSE00000783612	186675820	186675927
ENSE00000783613	186676813	186676935
ENSE00000934420	186602021	186602151
ENSE00000934421	186622339	186622430
ENSE00000934422	186625473	186625587
ENSE00000934423	186630797	186630858
ENSE00000934424	186633329	186633374
ENSE00000934425	186636082	186636207
ENSE00000934426	186637065	186637109
ENSE00000934427	186638277	186638320
ENSE00000934428	186638409	186638465
ENSE00000934429	186640915	186640967
ENSE00000934430	186641386	186641588
ENSE00000934431	186646686	186646877
ENSE00000934432	186659038	186659175
ENSE00000934433	186663768	186663835
ENSE00000934434	186664494	186664641
ENSE00003568137	186665126	186665218
ENSE00003595945	186666704	186666783
ENSE00003618919	186667150	186667230
ENSE00003653171	186668762	186668920
ENSE00003687186	186669701	186669814
ENSE00003968888	186677197	186680901
ENSE00003968894	186590056	186590523

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 99.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 62.4725 / max 1303.0842, expressed in 1809 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
24110	58.6891	1809
24113	2.2638	1072
24112	1.0669	645
24111	0.4526	219

Top tissues by expression

301 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
pigmented layer of retina	UBERON:0001782	99.91	gold quality
retina	UBERON:0000966	99.89	gold quality
choroid plexus epithelium	UBERON:0003911	99.66	gold quality
germinal epithelium of ovary	UBERON:0001304	99.38	gold quality
tibia	UBERON:0000979	99.29	gold quality
heart right ventricle	UBERON:0002080	99.19	gold quality
skin of hip	UBERON:0001554	99.13	gold quality
visceral pleura	UBERON:0002401	99.13	gold quality
renal glomerulus	UBERON:0000074	99.07	gold quality
metanephric glomerulus	UBERON:0004736	98.95	gold quality
blood vessel layer	UBERON:0004797	98.92	gold quality
parietal pleura	UBERON:0002400	98.75	gold quality
synovial joint	UBERON:0002217	98.72	gold quality
pleura	UBERON:0000977	98.67	gold quality
periodontal ligament	UBERON:0008266	98.62	gold quality
superficial temporal artery	UBERON:0001614	98.58	gold quality
upper leg skin	UBERON:0004262	98.54	gold quality
renal medulla	UBERON:0000362	98.28	gold quality
decidua	UBERON:0002450	98.27	gold quality
adrenal tissue	UBERON:0018303	98.21	gold quality
inferior vagus X ganglion	UBERON:0005363	98.18	gold quality
seminal vesicle	UBERON:0000998	98.16	gold quality
epithelium of nasopharynx	UBERON:0001951	98.15	gold quality
subthalamic nucleus	UBERON:0001906	98.06	gold quality
mammalian vulva	UBERON:0000997	97.99	gold quality
cauda epididymis	UBERON:0004360	97.94	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	97.91	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.90	gold quality
myocardium	UBERON:0002349	97.89	gold quality
stromal cell of endometrium	CL:0002255	97.88	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-11121	yes	851.78
E-MTAB-6108	yes	225.78
E-CURD-112	yes	19.22
E-GEOD-135922	yes	14.60
E-GEOD-124858	no	668.13
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): DIDO1, ETS1, FOSL1, HOXD3, ITGB8, JUND, SP1, SP3

miRNA regulators (miRDB)

237 targeting ITGAV, 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-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-1193	100.00	65.93	529
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-433-3P	99.98	69.37	1203
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548P	99.98	72.25	3784

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 44.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• integrin alphavbeta3 is shown to interact with PECAM-1 (PMID:10982404)
• Processing of integrin alpha(v) subunit by membrane type 1 matrix metalloproteinase stimulates migration of breast carcinoma cells on vitronectin (PMID:11724803)
• Acute hyperglycaemia induces an up-regulation of seven major genes, four of which were not previously reported in the literature. Northern blot analyses, performed on these 4 genes, confirm macroarrays results for alphav, beta4, c-myc, and MUC18. (PMID:11848444)
• Review. Alpha(v)beta3 integrins are involved in vascular repair processes. The challenge is to develop a therapeutic agent that will prove effective in reducing restenosis in humans following percutaneous coronary intervention (PCI). (PMID:11858476)
• They analyzed the expression of these cell surface receptors in nine ovarian cancer cell lines and also in the primary human ovarian surface epithelial cell line (HOSE). (PMID:11872628)
• Chemotaxis and chemoinvasion analyses revealed a dose-dependent increase in prostate cancer cell movement induced by osteopontin and a strict dependence of cell invasion on alphavbeta3 integrin function. (PMID:11928818)
• Unique ability of integrin alpha(v)beta 3 to support tumor cell arrest under dynamic flow conditions (Integrin alpha-v beta-3) (PMID:11934894)
• Del1 mediates vascular smooth muscle cell adhesion, migration, and proliferation through interaction with integrin alpha(v)beta(3). (PMID:11959660)
• Factor XIII mediates adhesion of platelets to endothelial cells through alpha(v)beta(3) and glycoprotein IIb/IIIa integrins. (PMID:12031826)
• Acute cellular rejection following human heart transplantation is associated with increased expression (PMID:12099514)
• existence of an alpha V integrin/vitronectin connection in hepatocellular carcinoma and suggest that this connection may be an adverse prognostic factor. (PMID:12143051)
• Alpha(v)beta(3) integrin engagement enhances cell invasiveness in human multiple myeloma. (PMID:12161360)
• integrin alphaVbeta3 expression is reduced when ROR alpha is activated in prostate cancer cells (PMID:12168086)
• Integrin alphavbeta3. Expression of integrin alpha v beta 3 promotes the metastatic phenotype in human melanoma by supporting specific adhesive, invasive and migratory properties of the tumor cells (PMID:12198771)
• alpha v beta 3 integrin signaling through Shc recruitment in response to mechanical stimulation in human osteoblasts (PMID:12210725)
• phosphoinositide 3-kinase C2alpha was found to be differentially regulated by alpha(v)beta(3) engagement (PMID:12237112)
• promotion of integrin alpha Vbeta 3-dependent endothelial cell adhesion by PGE2 (PMID:12237321)
• identification of a new alphavbeta5 integrin-interacting motif that is highly conserved in the fas-1 domains of many proteins suggesting that fas-1 domain-containing proteins may perform their biological functions by interacting with integrins (PMID:12270930)
• induced alpha(v)beta(8) integrin expression mediated Fas-stimulated migration (PMID:12324452)
• identification of functional segments within the beta2I-domain (PMID:12324470)
• Data show clearly that integrin alpha(v)beta(3) interacts with the latency-associated peptide (LAPbeta1 and 3) RGD motif. (PMID:12358597)
• role in mediating pro-angiogenic activity of CYR61 (PMID:12364323)
• An autocrine loop of the integrin alpha(V)beta(3)/CD47 receptor complex and thrombospondin-1 is identified as the molecular coupling device between mechanical loading and apoptosis. (PMID:12370491)
• in patients with endometriosis a significant negative correlation was observed between luminal expression of eNOS and alpha(v)beta(3) integrin and between glandular expression of eNOS and luminal expression of alpha(v)beta(3) integrin (PMID:12372469)
• thrombin interacts with alphavbeta3 as demonstrated by direct binding of alphavbeta3 protein to immobilized thrombin. (PMID:12372811)
• Overexpression of integrin alphaV promotes human osteosarcoma cell populated collagen lattice contraction and cell movement. (PMID:12384999)
• activation state of alphaVbeta3 integrin is an important regulator of the duration of insulin-like growth factor I receptor phosphorylation and this regulation is mediated through changes in the subcellular localization of SHP-2 (PMID:12399420)
• Data show a novel mechanism by which ECM regulates membrane-type 1 matrix metalloproteinase (MT1-MMP) association with beta1 or alphavbeta3 integrins, thus modulating its internalization, activity, and function on human endothelial cells. (PMID:12427871)
• integrin alpha5beta1-mediated control of the levels of integrin alphaVbeta3 is important for the distribution of focal contacts (PMID:12486108)
• has a role in the early phase of liver metastasis (PMID:12553378)
• thymidine phosphorylase and 2-deoxyribose-induced focal adhesion kinase phosphorylation was blocked by the antibodies to integrins alpha 5 beta 1 and alpha v beta 3, directly linking their migration and signaling components (PMID:12639965)
• role in regulating cell proliferation through integrin-linked kinase (ILK) in ovarian cancer cells (PMID:12642872)
• decreased expression of endometrial integrin alphavbeta3 suggests that functional, but not morphological, endometrial defect may be one of the causes for the patients with unexplained infertility and recurrent IVF-ET failures (PMID:12645863)
• Alphavbeta3 integrin expression and pinopode formation in human endometrium are processes closely related to endometrial maturation; unlikely as targets for contraceptive approaches or fertility-promoting strategies (PMID:12660257)
• tumstatin binds to alpha v beta 3 integrin in a vitronectin/fibronectin/RGD cyclic peptide independent manner (PMID:12682293)
• Data suggest that this alphavbeta3 binding to alpha5-laminins is involved in the regulation of cellular responses to growth factors known to be involved in epithelial and endothelial development. (PMID:12691260)
• signaling through JAM-1 and alphavbeta3 is necessary for bFGF-induced angiogenesis. (PMID:12750158)
• Data provide the first evidence that alphavbeta3 integrin can generate apoptosis-stimulating signals. (PMID:12765524)
• alpha 5 beta 1 and alpha v beta 3 are both important but cell-specific fibrillin-1 receptors (PMID:12807887)
• integrin alphavbeta3 cooperates with metalloproteinase MMP-9 in regulating migration of metastatic breast cancer cells (PMID:12874388)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	itgav	ENSDARG00000006314
mus_musculus	Itgav	ENSMUSG00000027087
rattus_norvegicus	Itgav	ENSRNOG00000004912
drosophila_melanogaster	if	FBGN0001250
drosophila_melanogaster	mew	FBGN0004456
drosophila_melanogaster	ItgaPS4	FBGN0034005
drosophila_melanogaster	ItgaPS5	FBGN0034880
drosophila_melanogaster	scb	FBGN0286785
caenorhabditis_elegans		WBGENE00002081
caenorhabditis_elegans		WBGENE00003929

Paralogs (17): ITGAL (ENSG00000005844), ITGA3 (ENSG00000005884), ITGA2B (ENSG00000005961), ITGA8 (ENSG00000077943), ITGAE (ENSG00000083457), ITGA6 (ENSG00000091409), ITGA4 (ENSG00000115232), ITGA7 (ENSG00000135424), ITGA11 (ENSG00000137809), ITGAX (ENSG00000140678), ITGA10 (ENSG00000143127), ITGA9 (ENSG00000144668), ITGAD (ENSG00000156886), ITGA5 (ENSG00000161638), ITGA2 (ENSG00000164171), ITGAM (ENSG00000169896), ITGA1 (ENSG00000213949)

Protein

Protein identifiers

Integrin alpha-V — P06756 (reviewed: P06756)

Alternative names: Vitronectin receptor, Vitronectin receptor subunit alpha

All UniProt accessions (13): P06756, A0A8V8TKF7, A0A8V8TKG0, A0A8V8TKH9, A0A8V8TKI2, A0A8V8TKT8, A0A8V8TKU8, A0A8V8TLN8, A0A8V8TLP3, A0A8V8TLW4, A0A8V8TLW9, H7BZG1, L7RXH0

UniProt curated annotations — full annotation on UniProt →

Function. The alpha-V (ITGAV) integrins are receptors for vitronectin, cytotactin, fibronectin, fibrinogen, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin and vWF. They recognize the sequence R-G-D in a wide array of ligands. ITGAV:ITGB3 binds to fractalkine (CX3CL1) and may act as its coreceptor in CX3CR1-dependent fractalkine signaling. ITGAV:ITGB3 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling. ITGAV:ITGB3 binds to FGF1 and this binding is essential for FGF1 signaling. ITGAV:ITGB3 binds to FGF2 and this binding is essential for FGF2 signaling. ITGAV:ITGB3 binds to IGF1 and this binding is essential for IGF1 signaling. ITGAV:ITGB3 binds to IGF2 and this binding is essential for IGF2 signaling. ITGAV:ITGB3 binds to IL1B and this binding is essential for IL1B signaling. ITGAV:ITGB3 binds to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1. ITGAV:ITGB3 and ITGAV:ITGB6 act as receptors for fibrillin-1 (FBN1) and mediate R-G-D-dependent cell adhesion to FBN1. Integrin alpha-V/beta-6 or alpha-V/beta-8 (ITGAV:ITGB6 or ITGAV:ITGB8) mediates R-G-D-dependent release of transforming growth factor beta-1 (TGF-beta-1) from regulatory Latency-associated peptide (LAP), thereby playing a key role in TGF-beta-1 activation. ITGAV:ITGB3 acts as a receptor for CD40LG. ITGAV:ITGB3 acts as a receptor for IBSP and promotes cell adhesion and migration to IBSP. (Microbial infection) Integrin ITGAV:ITGB5 acts as a receptor for Adenovirus type C. (Microbial infection) Integrin ITGAV:ITGB5 and ITGAV:ITGB3 act as receptors for Coxsackievirus A9 and B1. (Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for Herpes virus 8/HHV-8. (Microbial infection) Integrin ITGAV:ITGB6 acts as a receptor for herpes simplex 1/HHV-1. (Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for Human parechovirus 1. (Microbial infection) Integrin ITGAV:ITGB3 acts as a receptor for West nile virus. (Microbial infection) In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi’s sarcoma lesions.

Subunit / interactions. Heterodimer of an alpha and a beta subunit. The alpha subunit is composed of a heavy and a light chain linked by a disulfide bond. Alpha-V (ITGAV) associates with either beta-1 (ITGB1), beta-3 (ITGB3), beta-5 (ITGB5), beta-6 (ITGB6) or beta-8 (ITGB8). Interacts with CIB1. Interacts with RAB25. Integrins ITGAV:ITGB3 and ITGAV:ITGB5 interact with FBLN5 (via N-terminus). ITGAV:ITGB3 and ITGAV:ITGB5 interact with CCN3. ITGAV:ITGB3 interacts with ADGRA2. ITGAV:ITGB3 interacts with FGF2; it is likely that FGF2 can simultaneously bind ITGAV:ITGB3 and FGF receptors. ITGAV:ITGB3 interacts with IL1B. ITGAV:ITGB3 interacts with SELP (via C-type lectin domain); the interaction mediates cell-cell interaction and adhesion. ITGAV:ITGB3 is found in a ternary complex with CX3CR1 and CX3CL1. ITGAV:ITGB3 is found in a ternary complex with NRG1 and ERBB3. ITGAV:ITGB3 is found in a ternary complex with FGF1 and FGFR1. ITGAV:ITGB3 is found in a ternary complex with IGF1 and IGF1R. ITGAV:ITGB3 interacts with IGF2. ITGAV:ITGB3 and ITGAV:ITGB6 interact with FBN1. ITGAV:ITGB3 interacts with CD9, CD81 and CD151 (via second extracellular domain). ITGAV:ITGB6 interacts with TGFB1. ITGAV:ITGB3 interacts with PTN. Forms a complex with PTPRZ1 and PTN that stimulates endothelial cell migration through ITGB3 ‘Tyr-773’ phosphorylation. Interacts with TM4SF19. ITGAV:ITGB3 interacts with Bothrops moojeni disintegrin Moojecin; the interaction may inhibit ADP-induced platelet aggregation in human plasma. (Microbial infection) Integrin ITGAV:ITGB3 interacts with herpes virus 8/HHV-8 envelope glycoprotein B. (Microbial infection) Integrin ITGAV:ITGB3 and ITGAV:ITGB6 bind to coxsackievirus A9 and coxsackievirus B1 capsid proteins. (Microbial infection) Integrin ITGAV:ITGB6 interacts with herpes simplex 1/HHV-1 envelope glycoprotein H. (Microbial infection) Integrin ITGAV:ITGB3 interacts with Herpes simplex 2/HHV-2 envelope glycoprotein H. (Microbial infection) Integrin ITGAV:ITGB5 interacts with adenovirus type C penton protein. (Microbial infection) Integrin ITGAV:ITGB3 interacts with Human parechovirus 1 capsid proteins. (Microbial infection) Integrin ITGAV:ITGB3 interacts with West nile virus envelope protein E. (Microbial infection) Interacts with HIV-1 Tat.

Subcellular location. Cell membrane. Cell junction. Focal adhesion.

Miscellaneous. The constitutive activation of ITGAV:ITGB3 on neoplastic cells may contribute to tumor growth and metastatic potential.

Similarity. Belongs to the integrin alpha chain family.

Isoforms (3)

UniProt ID	Names	Canonical?
P06756-1	1	yes
P06756-2	2
P06756-3	3

RefSeq proteins (3): NP_001138471, NP_001138472, NP_002201* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000413	Integrin_alpha	Family
IPR013517	FG-GAP	Repeat
IPR013519	Int_alpha_beta-p	Repeat
IPR013649	Integrin_alpha_Ig-like_1	Domain
IPR018184	Integrin_alpha_C_CS	Conserved_site
IPR028994	Integrin_alpha_N	Homologous_superfamily
IPR032695	Integrin_dom_sf	Homologous_superfamily
IPR048285	Integrin_alpha_Ig-like_2	Domain
IPR048286	Integrin_alpha_Ig-like_3	Domain

Pfam: PF00357, PF01839, PF08441, PF20805, PF20806

UniProt features (176 total): strand 90, binding site 20, glycosylation site 13, turn 10, disulfide bond 9, helix 8, repeat 7, chain 3, sequence variant 3, sequence conflict 3, topological domain 2, splice variant 2, signal peptide 1, region of interest 1, short sequence motif 1, compositionally biased region 1, transmembrane region 1, mutagenesis site 1

Structure

Experimental structures (PDB)

59 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9CZD	X-RAY DIFFRACTION	2.23
5FFG	X-RAY DIFFRACTION	2.25
8W30	X-RAY DIFFRACTION	2.45
9CZA	X-RAY DIFFRACTION	2.49
4UM9	X-RAY DIFFRACTION	2.5
9CZF	X-RAY DIFFRACTION	2.53
9CZ7	X-RAY DIFFRACTION	2.57
6OM1	X-RAY DIFFRACTION	2.66
8VS6	ELECTRON MICROSCOPY	2.73
6OM2	X-RAY DIFFRACTION	2.77
9IUJ	ELECTRON MICROSCOPY	2.78
9LT3	ELECTRON MICROSCOPY	2.79
8XEL	ELECTRON MICROSCOPY	2.8
8XFG	ELECTRON MICROSCOPY	2.8
4UM8	X-RAY DIFFRACTION	2.85
9IND	ELECTRON MICROSCOPY	2.88
9XMM	ELECTRON MICROSCOPY	2.88
3IJE	X-RAY DIFFRACTION	2.9
4G1M	X-RAY DIFFRACTION	2.9
8TCF	ELECTRON MICROSCOPY	2.9
8XEI	ELECTRON MICROSCOPY	2.9
8XEK	ELECTRON MICROSCOPY	2.9
4G1E	X-RAY DIFFRACTION	3
8IJ5	ELECTRON MICROSCOPY	3
8XER	ELECTRON MICROSCOPY	3
8XFO	ELECTRON MICROSCOPY	3
6MK0	X-RAY DIFFRACTION	3
8ZDG	ELECTRON MICROSCOPY	3.03
1JV2	X-RAY DIFFRACTION	3.1
1U8C	X-RAY DIFFRACTION	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P06756-F1	88.21	0.72

Antibody-complex structures (SAbDab): 8 — 4O02, 6AVQ, 6AVR, 6AVU, 6DJP, 6UJB, 6UJC, 9IND

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (20): 260; 262; 264; 266; 268; 314; 316; 318; 320; 322; 379; 381 …

Disulfide bonds (9): 89–97, 138–158, 172–185, 491–502, 508–565, 626–632, 698–711, 852–914, 904–909

Glycosylation sites (13): 74, 290, 296, 488, 554, 615, 704, 835, 851, 874, 945, 973, 980

Mutagenesis-validated functional residues (1):

Position	Phenotype
1020–1021	increases ligand-binding activity.

Function

Pathways and Gene Ontology

Reactome pathways

35 pathways

ID	Pathway
R-HSA-1236973	Cross-presentation of particulate exogenous antigens (phagosomes)
R-HSA-1566948	Elastic fibre formation
R-HSA-210990	PECAM1 interactions
R-HSA-2129379	Molecules associated with elastic fibres
R-HSA-216083	Integrin cell surface interactions
R-HSA-2173789	TGF-beta receptor signaling activates SMADs
R-HSA-3000157	Laminin interactions
R-HSA-3000170	Syndecan interactions
R-HSA-3000178	ECM proteoglycans
R-HSA-4420097	VEGFA-VEGFR2 Pathway
R-HSA-445144	Signal transduction by L1
R-HSA-6798695	Neutrophil degranulation
R-HSA-9856532	Mechanical load activates signaling by PIEZO1 and integrins in osteocytes
R-HSA-9860927	Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells
R-HSA-109582	Hemostasis
R-HSA-1236975	Antigen processing-Cross presentation
R-HSA-1266738	Developmental Biology
R-HSA-1280218	Adaptive Immune System
R-HSA-1474244	Extracellular matrix organization
R-HSA-162582	Signal Transduction
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-170834	Signaling by TGF-beta Receptor Complex
R-HSA-194138	Signaling by VEGF
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-3000171	Non-integrin membrane-ECM interactions
R-HSA-373760	L1CAM interactions
R-HSA-422475	Axon guidance
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases

MSigDB gene sets: 579 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_REGULATION_OF_LIPID_STORAGE, GOBP_EPITHELIUM_DEVELOPMENT, PID_S1P_S1P1_PATHWAY, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX, BIOCARTA_EDG1_PATHWAY, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_LIPOPROTEIN_METABOLIC_PROCESS, REACTOME_CLASS_I_MHC_MEDIATED_ANTIGEN_PROCESSING_PRESENTATION, GOBP_FORMATION_OF_PRIMARY_GERM_LAYER, GOCC_SECRETORY_GRANULE, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOCC_CELL_SURFACE

GO Biological Process (40): angiogenesis (GO:0001525), vasculogenesis (GO:0001570), cell adhesion (GO:0007155), cell-matrix adhesion (GO:0007160), positive regulation of cytosolic calcium ion concentration (GO:0007204), integrin-mediated signaling pathway (GO:0007229), positive regulation of cell population proliferation (GO:0008284), negative regulation of macrophage derived foam cell differentiation (GO:0010745), negative regulation of lipid storage (GO:0010888), negative regulation of low-density lipoprotein particle clearance (GO:0010989), cell migration (GO:0016477), positive regulation of cell migration (GO:0030335), cell-substrate adhesion (GO:0031589), negative regulation of lipid transport (GO:0032369), cell adhesion mediated by integrin (GO:0033627), positive regulation of osteoblast proliferation (GO:0033690), heterotypic cell-cell adhesion (GO:0034113), substrate adhesion-dependent cell spreading (GO:0034446), wound healing, spreading of epidermal cells (GO:0035313), endodermal cell differentiation (GO:0035987), apolipoprotein A-I-mediated signaling pathway (GO:0038027), apoptotic cell clearance (GO:0043277), positive regulation of cell adhesion (GO:0045785), symbiont entry into host cell (GO:0046718), negative regulation of lipoprotein metabolic process (GO:0050748), regulation of phagocytosis (GO:0050764), negative chemotaxis (GO:0050919), positive regulation of small GTPase mediated signal transduction (GO:0051057), ERK1 and ERK2 cascade (GO:0070371), calcium ion transmembrane transport (GO:0070588), transforming growth factor beta production (GO:0071604), entry into host cell by a symbiont-containing vacuole (GO:0085017), extrinsic apoptotic signaling pathway in absence of ligand (GO:0097192), cell-cell adhesion (GO:0098609), positive regulation of intracellular signal transduction (GO:1902533), negative regulation of entry of bacterium into host cell (GO:2000536), negative regulation of extrinsic apoptotic signaling pathway (GO:2001237), blood vessel development (GO:0001568), formation of primary germ layer (GO:0001704), tissue development (GO:0009888)

GO Molecular Function (18): virus receptor activity (GO:0001618), opsonin binding (GO:0001846), fibronectin binding (GO:0001968), protease binding (GO:0002020), protein kinase C binding (GO:0005080), integrin binding (GO:0005178), coreceptor activity (GO:0015026), signaling receptor activity (GO:0038023), metal ion binding (GO:0046872), transforming growth factor beta binding (GO:0050431), extracellular matrix binding (GO:0050840), extracellular matrix protein binding (GO:1990430), signaling receptor binding (GO:0005102), protein binding (GO:0005515), fibroblast growth factor binding (GO:0017134), C-X3-C chemokine binding (GO:0019960), insulin-like growth factor I binding (GO:0031994), neuregulin binding (GO:0038132)

GO Cellular Component (23): cytosol (GO:0005829), plasma membrane (GO:0005886), focal adhesion (GO:0005925), integrin complex (GO:0008305), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), membrane (GO:0016020), lamellipodium membrane (GO:0031258), filopodium membrane (GO:0031527), microvillus membrane (GO:0031528), ruffle membrane (GO:0032587), integrin alphav-beta1 complex (GO:0034682), integrin alphav-beta3 complex (GO:0034683), integrin alphav-beta5 complex (GO:0034684), integrin alphav-beta6 complex (GO:0034685), integrin alphav-beta8 complex (GO:0034686), specific granule membrane (GO:0035579), alphav-beta3 integrin-PKCalpha complex (GO:0035866), alphav-beta3 integrin-IGF-1-IGF1R complex (GO:0035867), alphav-beta3 integrin-HMGB1 complex (GO:0035868), phagocytic vesicle (GO:0045335), extracellular exosome (GO:0070062), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Extracellular matrix organization	4
Antigen processing-Cross presentation	1
Cell surface interactions at the vascular wall	1
Elastic fibre formation	1
Signaling by TGF-beta Receptor Complex	1
Non-integrin membrane-ECM interactions	1
Signaling by VEGF	1
L1CAM interactions	1
Innate Immune System	1
Cellular responses to mechanical stimuli	1
Response of endothelial cells to shear stress	1
Class I MHC mediated antigen processing & presentation	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
integrin complex	5
protein binding	4
cell projection membrane	4
growth factor binding	3
cellular anatomical structure	3
plasma membrane protein complex	3
blood vessel morphogenesis	2
cell differentiation	2
cell-substrate adhesion	2
negative regulation of lipid localization	2
cell adhesion	2
binding	2
leading edge membrane	2
anatomical structure formation involved in morphogenesis	1
cellular process	1
regulation of biological quality	1
cell surface receptor signaling pathway	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
macrophage derived foam cell differentiation	1
regulation of macrophage derived foam cell differentiation	1
negative regulation of cell differentiation	1
regulation of lipid storage	1
lipid storage	1
negative regulation of cellular process	1
negative regulation of lipoprotein particle clearance	1
regulation of low-density lipoprotein particle clearance	1
low-density lipoprotein particle clearance	1
cell motility	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
lipid transport	1
regulation of lipid transport	1
negative regulation of transport	1
positive regulation of cell population proliferation	1
osteoblast proliferation	1
regulation of osteoblast proliferation	1
cell-cell adhesion	1

Protein interactions and networks

STRING

2766 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ITGAV	VTN	P01141	999
ITGAV	ITGB3	P05106	999
ITGAV	FN1	P02751	997
ITGAV	ITGB1	P05556	994
ITGAV	SPP1	P10451	990
ITGAV	ITGB5	P18084	990
ITGAV	MFGE8	Q08431	976
ITGAV	ITGB8	P26012	925
ITGAV	ITGB2	P05107	890
ITGAV	ITGB6	P18564	871
ITGAV	CD44	P16070	842
ITGAV	IBSP	P21815	837
ITGAV	VWF	P04275	834
ITGAV	CD36	P16671	794
ITGAV	SCARB2	Q14108	794
ITGAV	SCARB1	Q8WTV0	794

IntAct

138 interactions, top by confidence:

A	B	Type	Score
ITGAV	ITGB3	psi-mi:“MI:0407”(direct interaction)	0.930
ITGB3	ITGAV	psi-mi:“MI:0407”(direct interaction)	0.930
ITGB3	ITGAV	psi-mi:“MI:0915”(physical association)	0.930
ITGAV	ITGB3	psi-mi:“MI:0915”(physical association)	0.930
ITGAV	ITGB6	psi-mi:“MI:0407”(direct interaction)	0.800
FN1	ITGB3	psi-mi:“MI:0915”(physical association)	0.750
FN1	ITGB3	psi-mi:“MI:0407”(direct interaction)	0.750
ITGB3	FN1	psi-mi:“MI:0915”(physical association)	0.750
ITGAV	FN1	psi-mi:“MI:0915”(physical association)	0.740
B3GNT3	PGRMC1	psi-mi:“MI:0914”(association)	0.670
FGG	ITGB3	psi-mi:“MI:0915”(physical association)	0.660
KCNJ2	KCNJ18	psi-mi:“MI:2364”(proximity)	0.660
ITGAV	VTN	psi-mi:“MI:0915”(physical association)	0.560
SERPINH1	ITGAV	psi-mi:“MI:0915”(physical association)	0.560
PRKACA	ITGAV	psi-mi:“MI:0915”(physical association)	0.560
RAD23A	ITGAV	psi-mi:“MI:0915”(physical association)	0.560
TGFBR2	ITGAV	psi-mi:“MI:0915”(physical association)	0.560
LRRK1	ITGAV	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (232): ITGAV (Affinity Capture-MS), ITGAV (Affinity Capture-MS), ITGAV (Affinity Capture-MS), ITGAV (Affinity Capture-MS), ITGB1 (Co-fractionation), PSMD12 (Co-fractionation), ITGAV (Reconstituted Complex), LGALS3BP (Reconstituted Complex), ITGAV (Affinity Capture-Western), ITGAV (Affinity Capture-MS), ITGAV (Affinity Capture-MS), ITGAV (Synthetic Lethality), ITGAV (Biochemical Activity), NCOR1 (Affinity Capture-Western), NCOR2 (Affinity Capture-Western)

ESM2 similar proteins: A0AAQ4VMX2, A0RZC6, A8K7I4, C9XI63, C9XI66, I2C090, J3S836, P01023, P01024, P01025, P01026, P01027, P01029, P01030, P01031, P06684, P06756, P08649, P08650, P0C0L4, P0C0L5, P12247, P12387, P19069, P20740, P26007, P26008, P56652, P80746, P97280, P98093, Q01833, Q06033, Q0ZZJ6, Q2UVX4, Q3UU35, Q5RB37, Q61704, Q61739, Q63041

Diamond homologs: A2ARA8, O70362, P06756, P08514, P08648, P11688, P12080, P26008, P26009, P34446, P43406, P53708, P53711, P80108, P80109, P80746, Q06274, Q27977, Q61739, Q86AV9, Q8R2H5, Q9QUM0, A8X3A7, Q63258, P20702, P61625, Q9QXH4, P17852, P23229, P26007, P47014, Q00651, Q03600, Q13683, Q13797, Q24247, Q61738, Q62470, Q9W1M8, F1MMS9

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
ITGAV	“form complex”	“Av/b1 integrin”	binding
ITGAV	“form complex”	“Av/b2 integrin”	binding
ITGAV	“form complex”	“Av/b3 integrin”	binding
ITGAV	“form complex”	“Av/b5 integrin”	binding
ITGAV	“form complex”	“Av/b6 integrin”	binding
ITGAV	“form complex”	“Av/b8 integrin”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 126 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
p130Cas linkage to MAPK signaling for integrins	5	44.3×	4e-06
GRB2:SOS provides linkage to MAPK signaling for Integrins	5	41.5×	5e-06
Molecules associated with elastic fibres	9	32.3×	3e-09
TGF-beta receptor signaling activates SMADs	8	30.4×	4e-08
Syndecan interactions	6	29.5×	3e-06
Elastic fibre formation	7	27.3×	5e-07
Integrin signaling	5	24.6×	7e-05
Signaling by TGF-beta Receptor Complex	8	18.6×	8e-07

GO biological processes:

GO term	Partners	Fold	FDR
cell adhesion mediated by integrin	7	42.5×	1e-07
integrin-mediated signaling pathway	15	21.7×	3e-13
transforming growth factor beta receptor signaling pathway	10	14.3×	5e-07
positive regulation of epithelial to mesenchymal transition	5	14.3×	2e-03
cell-matrix adhesion	9	13.3×	5e-06
response to wounding	5	10.0×	7e-03
positive regulation of angiogenesis	7	7.3×	4e-03
positive regulation of cell migration	12	6.7×	4e-05

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — STAD.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	1
Uncertain significance	140
Likely benign	14
Benign	5

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
2663809	NM_002210.5(ITGAV):c.432G>C (p.Trp144Cys)	Pathogenic
2663810	NM_002210.5(ITGAV):c.1136A>T (p.Asp379Val)	Pathogenic
4823282	NM_002210.5(ITGAV):c.1719+1G>A	Pathogenic
3256934	NM_002210.5(ITGAV):c.903+1G>C	Likely pathogenic

SpliceAI

4382 predictions. Top by Δscore:

Variant	Effect	Δscore
2:186590524:G:GG	donor_gain	1.0000
2:186602019:A:AG	acceptor_gain	1.0000
2:186602019:AGCC:A	acceptor_gain	1.0000
2:186602020:G:GG	acceptor_gain	1.0000
2:186602020:GCCG:G	acceptor_gain	1.0000
2:186602147:AACAG:A	donor_loss	1.0000
2:186602149:CAGGT:C	donor_loss	1.0000
2:186602150:AGG:A	donor_loss	1.0000
2:186602151:GG:G	donor_loss	1.0000
2:186602152:GTAA:G	donor_loss	1.0000
2:186602153:T:A	donor_loss	1.0000
2:186618399:A:G	donor_gain	1.0000
2:186619620:A:G	donor_gain	1.0000
2:186622334:TTTA:T	acceptor_loss	1.0000
2:186622335:TTA:T	acceptor_loss	1.0000
2:186622337:A:AG	acceptor_gain	1.0000
2:186622338:G:GA	acceptor_gain	1.0000
2:186622338:GGCA:G	acceptor_gain	1.0000
2:186622429:TGG:T	donor_loss	1.0000
2:186622431:G:C	donor_loss	1.0000
2:186622431:G:GG	donor_gain	1.0000
2:186622433:GA:G	donor_loss	1.0000
2:186622434:AGTCT:A	donor_loss	1.0000
2:186630795:A:AG	acceptor_gain	1.0000
2:186630796:G:GG	acceptor_gain	1.0000
2:186630796:GAA:G	acceptor_gain	1.0000
2:186630859:G:GG	donor_gain	1.0000
2:186633314:T:TA	acceptor_gain	1.0000
2:186633316:T:TA	acceptor_gain	1.0000
2:186633327:A:AG	acceptor_gain	1.0000

AlphaMissense

6870 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:186625477:G:A	C138Y	1.000
2:186625478:T:G	C138W	1.000
2:186625536:T:C	C158R	1.000
2:186625537:G:A	C158Y	1.000
2:186625538:C:G	C158W	1.000
2:186625578:T:A	C172S	1.000
2:186625578:T:C	C172R	1.000
2:186625579:G:A	C172Y	1.000
2:186625579:G:C	C172S	1.000
2:186630826:T:A	C185S	1.000
2:186630826:T:C	C185R	1.000
2:186630827:G:A	C185Y	1.000
2:186630827:G:C	C185S	1.000
2:186630828:T:G	C185W	1.000
2:186633374:G:C	G211R	1.000
2:186633374:G:T	G211C	1.000
2:186638315:G:A	G281R	1.000
2:186638315:G:C	G281R	1.000
2:186638316:G:A	G281E	1.000
2:186640931:G:A	G307E	1.000
2:186663786:T:A	C626S	1.000
2:186663787:G:A	C626Y	1.000
2:186663787:G:C	C626S	1.000
2:186663804:T:A	C632S	1.000
2:186663804:T:C	C632R	1.000
2:186663805:G:A	C632Y	1.000
2:186663805:G:C	C632S	1.000
2:186664586:T:C	L673P	1.000
2:186665183:T:A	C711S	1.000
2:186665183:T:C	C711R	1.000

dbSNP variants (sampled 300 via entrez): RS1000004330 (2:186620054 C>CTG), RS1000007969 (2:186673732 A>G), RS1000029962 (2:186678439 A>G,T), RS1000072850 (2:186671291 T>A), RS1000092883 (2:186598136 C>A,T), RS1000157550 (2:186591154 C>G,T), RS1000173055 (2:186636872 C>G), RS1000191584 (2:186645844 C>T), RS1000249629 (2:186601289 C>A,T), RS1000254305 (2:186608770 G>T), RS1000291345 (2:186642509 T>C), RS1000308533 (2:186598221 G>A,T), RS1000338524 (2:186588573 G>C), RS1000365790 (2:186648408 A>G), RS1000424630 (2:186639603 G>C)

Disease associations

OMIM: gene MIM:193210 | disease phenotypes: MIM:621375

GenCC curated gene-disease

Mondo (1): immune dysregulation, neurodevelopmental defects, and colitis (MONDO:0980702)

Orphanet (0):

HPO phenotypes

39 total (30 of 39 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000175	Cleft palate
HP:0000193	Bifid uvula
HP:0000252	Microcephaly
HP:0000488	Retinopathy
HP:0000568	Microphthalmia
HP:0001047	Atopic dermatitis
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001382	Joint hypermobility
HP:0001511	Intrauterine growth retardation
HP:0001545	Anteriorly placed anus
HP:0001581	Recurrent skin infections
HP:0001627	Abnormal heart morphology
HP:0001880	Increased total eosinophil count
HP:0002119	Ventriculomegaly
HP:0002188	Delayed CNS myelination
HP:0002205	Recurrent respiratory infections
HP:0002583	Colitis
HP:0002720	Decreased circulating IgA concentration
HP:0002808	Kyphosis
HP:0002841	Recurrent fungal infections
HP:0003237	Increased circulating IgG concentration
HP:0003593	Infantile onset
HP:0004349	Reduced bone mineral density
HP:0005218	Anoperineal fistula
HP:0006989	Dysplastic corpus callosum
HP:0010479	Patent urachus
HP:0011003	High myopia

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST003253_8	Microalbuminuria	1.000000e-06
GCST003254_7	Urinary albumin-to-creatinine ratio in non-diabetics	4.000000e-06
GCST003255_5	Urinary albumin-to-creatinine ratio	8.000000e-07
GCST004131_3	Inflammatory bowel disease	1.000000e-08
GCST004132_87	Crohn’s disease	8.000000e-07
GCST007431_36	Lung function (FEV1/FVC)	5.000000e-14
GCST010043_101	Asthma	4.000000e-08
GCST90013421_3	Left-handedness	5.000000e-11

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007778	urinary albumin to creatinine ratio
EFO:0004713	FEV/FVC ratio
EFO:0009902	handedness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (10): CHEMBL1907598 (PROTEIN COMPLEX), CHEMBL2096675 (PROTEIN COMPLEX), CHEMBL2111407 (PROTEIN COMPLEX), CHEMBL2111416 (PROTEIN COMPLEX), CHEMBL2111425 (PROTEIN COMPLEX GROUP), CHEMBL2111443 (SELECTIVITY GROUP), CHEMBL3430892 (PROTEIN COMPLEX), CHEMBL3430893 (PROTEIN COMPLEX), CHEMBL3660 (SINGLE PROTEIN), CHEMBL4106150 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

8 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 377,027 (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
CHEMBL1174	EPTIFIBATIDE	4	17,269
CHEMBL428647	PACLITAXEL	4	332,542
CHEMBL916	TIROFIBAN	4	16,908
CHEMBL429876	CILENGITIDE	3	10,123
CHEMBL5315046	NESVATEGRAST	2	72
CHEMBL3319236	GLPG-0187	1	96
CHEMBL4241824	GSK-3008348 FREE BASE	1	8
CHEMBL4246089	GSK-3008348	1	9

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: catalytic receptor — Integrins

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
GSK3008348	Antagonist	10.8	pKd
MK-0429	Antagonist	7.1	pIC50
bexotegrast	Antagonist	5.47	pIC50

Binding affinities (BindingDB)

23 measured of 27 human assays (27 total across all organisms); most potent 23 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(S)-3-[3’-(2-cyclopropylamino-3,4-dioxo-cyclobut-1-enylamino)-biphenyl-4-yl]-2-((R)-7,7-dimethyl-2-oxo-bicyclo[2.2.1]heptane-1-sulfonylamino)-propionic acid	KI	0.1 nM
(3S)-3-[3-bromo-5-(trifluoromethyl)phenyl]-3-[[2-[[5-[(5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino]pyridine-3-carbonyl]amino]acetyl]amino]propanoic acid	IC50	0.3 nM	US-10035778: Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists
(3S)-3-[3-chloro-5-(difluoromethyl)phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido]propanoic acid	IC50	0.5 nM	US-10035778: Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists
(3S)-3-[3-bromo-5-methyl-phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido)propanoic acid	IC50	0.5 nM	US-10035778: Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists
(3S)-3-[3-bromo-5-chloro-phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido]propanoic acid	IC50	0.6 nM	US-10035778: Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists
(3S)-3-(3-bromo-5-chloro-phenyl)-3-[[2-[[5-[(5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino]pyridine-3-carbonyl]amino]acetyl]amino]propanoic acid	IC50	0.6 nM	US-10035778: Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists
(3S)-3-[3-bromo-5-fluoro-phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido)propanoic acid	IC50	0.6 nM	US-10035778: Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists
(3S)-3-(3,5-dibromophenyl)-3-[[2-[[5-[(5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino]pyridine-3-carbonyl]amino]acetyl]amino]propanoic acid	IC50	0.6 nM	US-10035778: Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists
(3S)-3-[3-bromo-5-(difluoromethyl)phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido]propanoic acid	IC50	0.7 nM	US-10035778: Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists
(3S)-3-[3-chloro-5-(trifluoromethyl)phenyl]3-[[2-[[5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino]pyridine-3-carbonyl]amino]acetyl]amino]propanoic acid	IC50	0.7 nM	US-10035778: Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists
(3S)-3-(3-bromo-5-(trifluoromethyl)phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido)propanoic acid	IC50	0.8 nM	US-10035778: Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists
(3S)-3-[3-chloro-5-(trifluoromethyl)phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido]propanoic acid	IC50	0.8 nM	US-10035778: Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists
(3S)-3-(3,5-dibromophenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido)propanoic acid	IC50	1 nM	US-10035778: Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists
(3S)-3-[3,5-bis(trifluoromethyl)phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido]propanoic acid	IC50	1 nM	US-10035778: Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists
(3S)-3-[3,5-dichloro-phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido)propanoic acid	IC50	1 nM	US-10035778: Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists
(3S)-3-[3-chloro-5-(trifluoromethoxy)phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido)propanoic acid	IC50	1 nM	US-10035778: Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists
(3S)-3-(3-bromo-5-(trifluoromethoxy)phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido)propanoic acid	IC50	1 nM	US-10035778: Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists
(S)-2-((S)-7,7-Dimethyl-2-oxo-bicyclo[2.2.1]hept-1-ylmethanesulfonylamino)-3-[3’-(3-propyl-ureido)-biphenyl-4-yl]-propionic acid	KI	1 nM
(3S)-3-[3-chloro-5-methyl-phenyl)-3-(2-(3-hydroxy-5-((5-hydroxy-1,4,5,6-tetrahydropyrimidin-2-yl)amino)benzamido)acetamido)propanoic acid	IC50	2 nM	US-10035778: Meta-azacyclic amino benzoic acid derivatives as pan integrin antagonists
(S)-2-(Adamantan-1-ylmethoxycarbonylamino)-3-{[5-(2-guanidinocarbonyl-cyclopropyl)-thiophene-2-carbonyl]-amino}-propionic acid	IC50	69 nM
(2R)-2-[[(6R)-4,5,6,7-tetrahydro-1H-indazole-6-carbonyl]amino]-4-[3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]cyclobutyl]oxybutanoic acid	IC50	150 nM	US-11180494: Substituted amino acids as integrin inhibitors
(S)-2-(Adamantan-1-ylmethoxycarbonylamino)-3-{[5-((E)-3-guanidino-3-oxo-propenyl)-thiophene-2-carbonyl]-amino}-propionic acid	IC50	1100 nM
CHEMBL3973646	IC50	2500 nM

ChEMBL bioactivities

3861 potent at pChembl≥5 of 4001 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Ki	0.01	nM	GSK-3008348 FREE BASE
10.80	Kd	0.01585	nM	GSK-3008348 FREE BASE
10.70	IC50	0.01995	nM	CHEMBL3962660
10.70	IC50	0.02	nM	CHEMBL3962660
10.70	Ki	0.01995	nM	CHEMBL4244784
10.70	Kd	0.02	nM	GSK-3008348 FREE BASE
10.60	Ki	0.02512	nM	CHEMBL4238909
10.52	IC50	0.03	nM	CHEMBL378530
10.52	IC50	0.03	nM	CHEMBL410050
10.50	Ki	0.03162	nM	CHEMBL4242263
10.48	IC50	0.033	nM	CHEMBL1180969
10.40	IC50	0.04	nM	CHEMBL151142
10.40	IC50	0.04	nM	CHEMBL267434
10.40	Ki	0.03981	nM	GSK-3008348 FREE BASE
10.40	Ki	0.03981	nM	CHEMBL4241584
10.40	Ki	0.03981	nM	CHEMBL4249629
10.40	Ki	0.03981	nM	CHEMBL4249172
10.40	Ki	0.03981	nM	GSK-3008348
10.40	IC50	0.04	nM	CHEMBL5268482
10.40	IC50	0.04	nM	CHEMBL357486
10.40	IC50	0.04	nM	CHEMBL116123
10.37	Ki	0.043	nM	CHEMBL2071603
10.30	Ki	0.05012	nM	CHEMBL4237919
10.26	IC50	0.055	nM	CHEMBL87372
10.25	IC50	0.056	nM	CHEMBL314636
10.24	IC50	0.058	nM	CHEMBL312929
10.22	Kd	0.06	nM	CHEMBL332914
10.22	IC50	0.06	nM	CHEMBL3893700
10.22	IC50	0.06	nM	CHEMBL4443665
10.20	IC50	0.0631	nM	CHEMBL3893700
10.20	Ki	0.0631	nM	CHEMBL4238909
10.20	Ki	0.0631	nM	CHEMBL4243367
10.20	Ki	0.0631	nM	CHEMBL4237868
10.20	Ki	0.0631	nM	CHEMBL4239085
10.20	IC50	0.063	nM	CHEMBL84578
10.15	IC50	0.07	nM	CHEMBL123262
10.15	IC50	0.07	nM	CHEMBL186552
10.10	IC50	0.08	nM	CHEMBL332914
10.10	IC50	0.08	nM	CHEMBL123374
10.10	IC50	0.08	nM	CHEMBL187289
10.10	Ki	0.07943	nM	CHEMBL4242635
10.10	Ki	0.07943	nM	CHEMBL4247149
10.10	Ki	0.07943	nM	CHEMBL4248589
10.10	IC50	0.08	nM	CHEMBL437072
10.10	IC50	0.08	nM	CHEMBL145085
10.09	IC50	0.082	nM	CHEMBL2153647
10.05	IC50	0.09	nM	CHEMBL1269295
10.00	IC50	0.1	nM	CHEMBL332914
10.00	IC50	0.1	nM	CHEMBL181758
10.00	Ki	0.1	nM	CHEMBL4251444

PubChem BioAssay actives

3157 with measured affinity, of 4395 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
3-[[2-[4-[(4-methyl-2-pyridinyl)amino]butanoylamino]acetyl]amino]-3-(4-naphthalen-1-ylphenyl)propanoic acid	1171325: Inhibition of integrin alphavbeta6 (unknown origin) by Merck binding assay	ic50	<0.0001	uM
(3S)-3-(3-morpholin-4-ylphenyl)-4-[(3R)-3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]pyrrolidin-1-yl]butanoic acid	1400456: Binding affinity to human integrin alphaVbeta6 assessed as dissociation constant up to 48 hrs by liquid scintillation counting	ki	<0.0001	uM
(3S)-3-[3-(3,5-dimethylpyrazol-1-yl)-5-morpholin-4-ylphenyl]-4-[(3R)-3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]pyrrolidin-1-yl]butanoic acid	1400434: Binding affinity to alphaVbeta6 (unknown origin) by radioligand binding assay	ki	<0.0001	uM
(3S)-3-[3-(2,5-dimethyl-1H-imidazol-4-yl)phenyl]-4-[(3R)-3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]pyrrolidin-1-yl]butanoic acid	1400434: Binding affinity to alphaVbeta6 (unknown origin) by radioligand binding assay	ki	<0.0001	uM
(2S)-2-[[(2S)-1-(benzenesulfonyl)pyrrolidine-2-carbonyl]amino]-3-[4-[4-(diaminomethylideneamino)butanoylamino]phenyl]propanoic acid	1324385: Inhibition of integrin alphaVbeta1 (unknown origin)-mediated CHO cell adhesion to fibronectin preincubated for 15 to 30 mins followed by 60 min incubation for adhesion by crystal violet staining based cell adhesion assay	ic50	<0.0001	uM
(3S)-3-[3-[(3S)-oxolan-3-yl]oxyphenyl]-4-[(3R)-3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]pyrrolidin-1-yl]butanoic acid	1400434: Binding affinity to alphaVbeta6 (unknown origin) by radioligand binding assay	ki	<0.0001	uM
(3S)-3-[3-(oxolan-3-yl)phenyl]-4-[(3R)-3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]pyrrolidin-1-yl]butanoic acid	1400434: Binding affinity to alphaVbeta6 (unknown origin) by radioligand binding assay	ki	<0.0001	uM
(3S)-4-[(3R)-3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]pyrrolidin-1-yl]-3-[3-(triazol-1-yl)phenyl]butanoic acid	1400434: Binding affinity to alphaVbeta6 (unknown origin) by radioligand binding assay	ki	<0.0001	uM
3-[[(5Z)-5-[(2-chloro-4,5-dimethoxyphenyl)methylidene]-3-methyl-4-oxo-1,3-thiazolidin-2-ylidene]amino]benzoic acid	266645: Inhibition of [125I]echistatin binding to integrin alphaVbeta3 receptor	ic50	<0.0001	uM
2-[(1S,4S,10S,13S)-10-[3-(diaminomethylideneamino)propyl]-3,6,9,12-tetraoxo-14-propanoyl-2,5,8,11,14-pentazabicyclo[11.2.1]hexadecan-4-yl]acetic acid	317269: Displacement of [125I]echistatin from human integrin alpha-V-beta-3 receptor high affinity state by solid phase assay	ic50	<0.0001	uM
(2S)-2-(benzenesulfonamido)-3-[[5-[2-[(diaminomethylideneamino)methyl]phenyl]thiophene-2-carbonyl]amino]propanoic acid;2,2,2-trifluoroacetic acid	220478: Inhibition of fibrinogen binding to integrin alphaV-beta3 receptor	ic50	<0.0001	uM
(3S)-3-[[2-[2-oxo-3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]pyrrolidin-1-yl]acetyl]amino]-3-quinolin-3-ylpropanoic acid	217313: Inhibition of Vitronectin receptor, integrin alphaV-beta3 expressed in HEK 293 cells	ic50	<0.0001	uM
2-[1-[2-[[4-(1H-benzimidazol-2-ylamino)cyclohexyl]methylamino]-2-oxoethyl]-2-oxo-4,5-dihydro-3H-1-benzazepin-5-yl]acetic acid	1924406: Antagonist activity against human integrin alphaVbeta3 expressed in CHO-K1 cells measured after 4 hrs by Cell adhesion assay	ic50	<0.0001	uM
2-[(2S,5R,8S,11S)-5-benzyl-8-[4-[3-[(2E)-2-[(2E,4E,6E)-7-[3-[3-[4-[(2S,5S,11S,14R)-14-benzyl-5-(3-carbamimidamidopropyl)-11-(carboxymethyl)-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]butylamino]-3-oxopropyl]-1,1-dimethylbenzo[e]indol-3-ium-2-yl]hepta-2,4,6-trienylidene]-1,1-dimethylbenzo[e]indol-3-yl]propanoylamino]butyl]-11-(3-carbamimidamidopropyl)-3,6,9,12,15-pentaoxo-1,4,7,10,13-pentazacyclopentadec-2-yl]acetic acid bromide	678142: Displacement of [125I]-c(RGDyK) from human integrin alphavbeta3 after 16 hrs by scintillation counting	ki	<0.0001	uM
(3S)-3-[3-(3,5-dimethylpyrazol-1-yl)phenyl]-4-[(3R)-3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]pyrrolidin-1-yl]butanoic acid	1400434: Binding affinity to alphaVbeta6 (unknown origin) by radioligand binding assay	ki	<0.0001	uM
(3S)-3-[3-(3,5-dimethylpyrazol-1-yl)phenyl]-4-[(3R)-3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]pyrrolidin-1-yl]butanoic acid;hydrochloride	1577126: Inhibition of integrin alphavbeta6 (unknown origin) by radioligand binding assay	ki	<0.0001	uM
(3S)-3-[[2-[(3S)-2-oxo-3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]pyrrolidin-1-yl]acetyl]amino]-3-quinolin-3-ylpropanoic acid	35526: Inhibition of high affinity radioligand binding to human alphaV-beta3 integrin	ic50	<0.0001	uM
(2S)-3-[[5-[3-(diaminomethylideneamino)phenyl]thiophene-2-carbonyl]amino]-2-[(2,4,6-trimethylphenyl)sulfonylamino]propanoic acid;2,2,2-trifluoroacetic acid	220605: Inhibition of fibrinogen binding to K562 cells expressing integrin alphaV-beta3	ic50	<0.0001	uM
(2S)-2-(benzenesulfonamido)-3-[[5-[3-[(diaminomethylideneamino)methyl]phenyl]thiophene-2-carbonyl]amino]propanoic acid	1177813: Antagonist activity at alphavbeta3 integrin receptor (unknown origin) by cell-based ELISA	ic50	<0.0001	uM
2-[7-[[4-(1,4,5,6-tetrahydropyrimidin-2-ylamino)butanoylamino]methyl]-8,9-dihydro-5H-benzo[7]annulen-9-yl]acetic acid	217444: Displacement of vitronectin from human integrin alphaV-beta5	ic50	0.0001	uM
(3S)-3-(2-methoxypyrimidin-5-yl)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid	242026: Inhibitory activity against alpha v beta-3 receptor using scintillation proximity assay (SPAV3)	ic50	0.0001	uM
(3S)-3-(2,3-dihydro-1-benzofuran-6-yl)-3-[2-oxo-3-[3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl]imidazolidin-1-yl]propanoic acid	220465: Inhibition of alphaV-beta3 integrin binding	ic50	0.0001	uM
(2S)-2-(benzenesulfonamido)-3-[[4-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]benzoyl]amino]propanoic acid	217313: Inhibition of Vitronectin receptor, integrin alphaV-beta3 expressed in HEK 293 cells	ic50	0.0001	uM
(2S)-3-[[3-fluoro-4-[4-(1,4,5,6-tetrahydropyrimidin-2-ylamino)piperidin-1-yl]benzoyl]amino]-2-[(4-hydroxyphenyl)sulfonylamino]propanoic acid	600449: Antagonist activity at alphavbeta3 integrin receptor	ic50	0.0001	uM
(2S)-3-[[4-[2-(6-amino-2-pyridinyl)ethyl]benzoyl]amino]-2-[(4-iodophenyl)sulfonylamino]propanoic acid	217313: Inhibition of Vitronectin receptor, integrin alphaV-beta3 expressed in HEK 293 cells	ic50	0.0001	uM
(2S)-3-[[1-[3-(1H-imidazol-2-ylamino)propyl]indazole-4-carbonyl]amino]-2-[(2,4,6-trimethylphenyl)sulfonylamino]propanoic acid	217308: Inhibition of Vitronectin receptor (alpha V beta 3) binding	ic50	0.0001	uM
(2S)-3-[[4-[2-(6-amino-2-pyridinyl)ethyl]benzoyl]amino]-2-(benzenesulfonamido)propanoic acid	217306: Inhibition of binding to human Vitronectin receptor (integrin alphaV-beta3)	ic50	0.0001	uM
3-[[2-[4-[(4-methyl-2-pyridinyl)amino]butanoylamino]acetyl]amino]-3-[3-(trifluoromethoxy)phenyl]propanoic acid	220626: Inhibition of fibronectin binding to recombinant human alphaV-beta6 integrin	ic50	0.0001	uM
(3S)-3-[(3R)-2-oxo-3-[3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propyl]pyrrolidin-1-yl]-3-quinolin-3-ylpropanoic acid	220466: Displacement of [125I]-labeled nonpeptide from purified recombinant human alphaV-beta3 integrin	ic50	0.0001	uM
(2S)-2-[[(2S)-1-(benzenesulfonyl)pyrrolidine-2-carbonyl]amino]-3-[4-[[3-(diaminomethylideneamino)benzoyl]amino]phenyl]propanoic acid	1324385: Inhibition of integrin alphaVbeta1 (unknown origin)-mediated CHO cell adhesion to fibronectin preincubated for 15 to 30 mins followed by 60 min incubation for adhesion by crystal violet staining based cell adhesion assay	ic50	0.0001	uM
(2S)-5-oxo-2-(phenylmethoxycarbonylamino)-5-[4-[3-(1,4,5,6-tetrahydropyrimidin-2-ylamino)phenyl]piperazin-1-yl]pentanoic acid	217305: Inhibitory activity was determined against human vitronectin receptor (alpha V beta 3)	ic50	0.0001	uM
(3S)-3-(3-cyclopropyl-5-morpholin-4-ylphenyl)-4-[(3R)-3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]pyrrolidin-1-yl]butanoic acid	1400434: Binding affinity to alphaVbeta6 (unknown origin) by radioligand binding assay	ki	0.0001	uM
(2S)-2-[[(2S)-1-(benzenesulfonyl)pyrrolidine-2-carbonyl]amino]-3-[4-[4-(4,5-dihydro-1H-imidazol-2-ylamino)butanoylamino]phenyl]propanoic acid	1324385: Inhibition of integrin alphaVbeta1 (unknown origin)-mediated CHO cell adhesion to fibronectin preincubated for 15 to 30 mins followed by 60 min incubation for adhesion by crystal violet staining based cell adhesion assay	ic50	0.0001	uM
(3S)-3-[3-[(3R)-oxolan-3-yl]oxyphenyl]-4-[(3R)-3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]pyrrolidin-1-yl]butanoic acid	1400434: Binding affinity to alphaVbeta6 (unknown origin) by radioligand binding assay	ki	0.0001	uM
(2S)-3-[[2-[[3-[4-(adamantane-1-carbonylamino)butanoylamino]-5-(diaminomethylideneamino)benzoyl]amino]acetyl]amino]-2-[[(2S)-1-(benzenesulfonyl)pyrrolidine-2-carbonyl]amino]propanoic acid	1698264: Inhibition of alphavbeta1 integrin (unknown origin) by solid phase binding assay	ic50	0.0001	uM
(3S)-3-[3-(3-methyl-1,2,4-triazol-4-yl)phenyl]-4-[(3R)-3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]pyrrolidin-1-yl]butanoic acid	1400434: Binding affinity to alphaVbeta6 (unknown origin) by radioligand binding assay	ki	0.0001	uM
(3S)-3-[3-(3,5-dimethyl-1,2,4-triazol-1-yl)phenyl]-4-[(3R)-3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]pyrrolidin-1-yl]butanoic acid	1400434: Binding affinity to alphaVbeta6 (unknown origin) by radioligand binding assay	ki	0.0001	uM
(3S)-3-[3-(3,5-dimethylpyrazol-1-yl)phenyl]-4-[(1S,3R)-1-methyl-3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]pyrrolidin-1-ium-1-yl]butanoate	1577126: Inhibition of integrin alphavbeta6 (unknown origin) by radioligand binding assay	ki	0.0001	uM
(3S)-3-[3-(3-methylpyrazol-1-yl)phenyl]-4-[(3R)-3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]pyrrolidin-1-yl]butanoic acid	1400434: Binding affinity to alphaVbeta6 (unknown origin) by radioligand binding assay	ki	0.0001	uM
(3S)-3-(3-pyrazol-1-ylphenyl)-4-[(3R)-3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]pyrrolidin-1-yl]butanoic acid	1400434: Binding affinity to alphaVbeta6 (unknown origin) by radioligand binding assay	ki	0.0001	uM
(3S)-3-[3-(5-methylpyrazol-1-yl)phenyl]-4-[(3R)-3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]pyrrolidin-1-yl]butanoic acid	1400434: Binding affinity to alphaVbeta6 (unknown origin) by radioligand binding assay	ki	0.0001	uM
(3S)-3-(3-cyclopropylphenyl)-4-[(3R)-3-[2-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)ethyl]pyrrolidin-1-yl]butanoic acid	1400434: Binding affinity to alphaVbeta6 (unknown origin) by radioligand binding assay	ki	0.0001	uM
2-[(3S,6S,12S,15S,21S,24R)-12-[3-(diaminomethylideneamino)propyl]-21-[4-[6-[3-(2,2-difluoro-10,12-dimethyl-3-aza-1-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-1(12),4,6,8,10-pentaen-4-yl)propanoylamino]hexanoylamino]butyl]-22-methyl-3,15-bis(2-methylpropyl)-2,5,8,11,14,17,20,23-octaoxo-1,4,7,10,13,16,19,22-octazabicyclo[22.3.0]heptacosan-6-yl]acetic acid	1614469: Inhibition of LAP binding to human integrin alphavbeta8 receptor after 1 hr by solid-phase binding assay	ic50	0.0001	uM
(2S)-3-[[2-[[3-[3-(adamantane-1-carbonylamino)propanoylamino]-5-(diaminomethylideneamino)benzoyl]amino]acetyl]amino]-2-[[(2S)-1-(benzenesulfonyl)pyrrolidine-2-carbonyl]amino]propanoic acid	1698264: Inhibition of alphavbeta1 integrin (unknown origin) by solid phase binding assay	ic50	0.0001	uM
(2S)-3-[[2-[[3-[[2-(adamantane-1-carbonylamino)acetyl]amino]-5-(diaminomethylideneamino)benzoyl]amino]acetyl]amino]-2-[[(2S)-1-(benzenesulfonyl)pyrrolidine-2-carbonyl]amino]propanoic acid	1698264: Inhibition of alphavbeta1 integrin (unknown origin) by solid phase binding assay	ic50	0.0001	uM
(2S)-3-[[2-[[3-[5-(adamantane-1-carbonylamino)pentanoylamino]-5-(diaminomethylideneamino)benzoyl]amino]acetyl]amino]-2-[[(2S)-1-(benzenesulfonyl)pyrrolidine-2-carbonyl]amino]propanoic acid	1698264: Inhibition of alphavbeta1 integrin (unknown origin) by solid phase binding assay	ic50	0.0001	uM
2-[(2S,5R,8S,11S)-5-benzyl-11-[3-(diaminomethylideneamino)propyl]-7-methyl-3,6,9,12,15-pentaoxo-8-propan-2-yl-1,4,7,10,13-pentazacyclopentadec-2-yl]acetic acid	256969: Displacement of [125I]-echistatin from alpha-v-beta-5 integrin receptor	ic50	0.0001	uM
2-(benzenesulfonamido)-3-[4-[[3-(1,4,5,6-tetrahydropyrimidin-2-ylamino)benzoyl]amino]phenyl]propanoic acid	35524: Binding affinity towards alpha V-beta3 receptor expressed in HEK293 cells	ic50	0.0001	uM
2-[(1S,4S,10S,13S)-10-[3-(diaminomethylideneamino)propyl]-14-heptyl-3,6,9,12-tetraoxo-2,5,8,11,14-pentazabicyclo[11.2.1]hexadecan-4-yl]acetic acid	317269: Displacement of [125I]echistatin from human integrin alpha-V-beta-3 receptor high affinity state by solid phase assay	ic50	0.0001	uM
3-[[2-[[5-(benzylcarbamoylamino)furan-2-carbonyl]amino]acetyl]amino]-3-pyridin-3-ylpropanoic acid	220303: Inhibitory activity against alphaV-beta3 integrin	ic50	0.0001	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases expression, increases abundance	4
Benzo(a)pyrene	decreases reaction, increases expression, affects binding, increases methylation	4
Air Pollutants	affects cotreatment, decreases expression, increases abundance, increases oxidation	3
Copper	decreases uptake, affects binding, increases expression, decreases abundance, decreases expression (+1 more)	3
Tobacco Smoke Pollution	affects expression, decreases expression	3
Tretinoin	increases cleavage, affects cotreatment, increases expression, affects binding	3
Valproic Acid	decreases methylation, increases expression	3
Aflatoxin B1	affects expression, increases methylation	3
Cadmium Chloride	increases expression, decreases reaction, increases abundance, increases palmitoylation, decreases expression	3
perfluorooctane sulfonic acid	decreases expression	2
chloropicrin	decreases expression	2
entinostat	affects cotreatment, decreases expression	2
lipopolysaccharide, Escherichia coli O111 B4	decreases reaction, increases expression, affects binding	2
Bortezomib	increases expression, affects cotreatment, decreases expression	2
Resveratrol	affects cotreatment, increases expression, affects binding, affects localization, increases reaction	2
Cisplatin	decreases abundance, decreases response to substance, decreases uptake, affects cotreatment, decreases expression	2
Dibutyl Phthalate	decreases expression, increases expression	2
Plant Extracts	affects cotreatment, increases expression, decreases reaction, increases abundance	2
Triterpenes	decreases reaction, increases expression, increases secretion, affects binding	2
Cyclosporine	decreases expression, increases expression	2
Particulate Matter	increases expression, decreases expression, increases abundance	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, decreases expression, increases oxidation	1
bisphenol A	decreases expression	1
sodium arsenate	decreases expression	1
titanium dioxide	increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, affects localization, increases expression	1

ChEMBL screening assays

592 unique, capped per target: 546 binding, 31 functional, 15 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1013695	Binding	Binding affinity to integrin alphaVbeta3 expressed in human K562 cells at 1 uM for 30 mins by flow cytometry	Discovery of targeting ligands for breast cancer cells using the one-bead one-compound combinatorial method. — J Med Chem
CHEMBL1786464	Functional	Antagonist activity at alphavbeta3 integrin receptor	Improvement in aqueous solubility in small molecule drug discovery programs by disruption of molecular planarity and symmetry. — J Med Chem
CHEMBL4001095	ADMET	Drug internalization in human EPC assessed as alphavbeta3-mediated drug uptake by measuring intracellular content per mg protein at 1 uM measured after 1 hr by HPLC-ESI-MS/MS analysis	Synthesis of Novel c(AmpRGD)-Sunitinib Dual Conjugates as Molecular Tools Targeting the αvβ3 Integrin/VEGFR2 Couple and Impairing Tumor-Associated Angiogenesis. — J Med Chem

Cellosaurus cell lines

11 cell lines: 9 cancer cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8IU	Abcam HCT 116 ITGAV KO	Cancer cell line	Male
CVCL_B8XP	Abcam MCF-7 ITGAV KO	Cancer cell line	Female
CVCL_B9L4	Abcam A-549 ITGAV KO	Cancer cell line	Male
CVCL_D8NI	Ubigene HCT 116 ITGAV KO	Cancer cell line	Male
CVCL_E4J4	Genomeditech HEK-293 H_alphaVbeta6	Transformed cell line	Female
CVCL_JX91	K562-AVB3	Cancer cell line	Female
CVCL_JY67	H357-V3	Cancer cell line	Male
CVCL_JY68	H357-VB6	Cancer cell line	Male
CVCL_JZ13	M21L4	Cancer cell line	Female
CVCL_JZ14	M21L22	Cancer cell line	Female

Clinical trials (associated diseases)

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