ITGA4

Summary

ITGA4 (integrin subunit alpha 4, HGNC:6140) is a protein-coding gene on chromosome 2q31.3, encoding Integrin alpha-4 (P13612). Integrins alpha-4/beta-1 (VLA-4) and alpha-4/beta-7 are receptors for fibronectin.

The gene encodes a member of the integrin alpha chain family of proteins. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain that function in cell surface adhesion and signaling. The encoded preproprotein is proteolytically processed to generate light and heavy chains that comprise the alpha 4 subunit. This subunit associates with a beta 1 or beta 7 subunit to form an integrin that may play a role in cell motility and migration. This integrin is a therapeutic target for the treatment of multiple sclerosis, Crohn’s disease and inflammatory bowel disease. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 3676 — RefSeq curated summary.

At a glance

• GWAS associations: 47
• Clinical variants (ClinVar): 179 total — 1 pathogenic, 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_000885

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6140
Approved symbol	ITGA4
Name	integrin subunit alpha 4
Location	2q31.3
Locus type	gene with protein product
Status	Approved
Aliases	CD49d
Ensembl gene	ENSG00000115232
Ensembl biotype	protein_coding
OMIM	192975
Entrez	3676

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 7 retained_intron, 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000233573, ENST00000339307, ENST00000397033, ENST00000465522, ENST00000468948, ENST00000473002, ENST00000476089, ENST00000476824, ENST00000478440, ENST00000484404, ENST00000490435

RefSeq mRNA: 2 — MANE Select: NM_000885 NM_000885, NM_001316312

CCDS: CCDS42788, CCDS82540

Canonical transcript exons

ENST00000397033 — 28 exons

Exon	Start	End
ENSE00000783326	181485881	181485992
ENSE00000783327	181493325	181493419
ENSE00000783330	181495783	181495937
ENSE00000783331	181498623	181498777
ENSE00000783338	181527297	181527387
ENSE00000783339	181529541	181529648
ENSE00000783340	181530524	181530649
ENSE00000783343	181534816	181534935
ENSE00000883087	181531657	181531776
ENSE00000883088	181534272	181534370
ENSE00001070439	181535432	181538940
ENSE00001918564	181457386	181457851
ENSE00003490392	181475159	181475288
ENSE00003495371	181458196	181458317
ENSE00003510047	181511699	181511775
ENSE00003524283	181509658	181509807
ENSE00003535123	181495371	181495416
ENSE00003554902	181494722	181494812
ENSE00003561651	181480137	181480266
ENSE00003573570	181524171	181524250
ENSE00003586175	181525202	181525291
ENSE00003599574	181481598	181481683
ENSE00003628298	181474960	181475066
ENSE00003646223	181482514	181482651
ENSE00003671544	181523437	181523532
ENSE00003678088	181522191	181522341
ENSE00003687565	181478757	181478824
ENSE00003688384	181482360	181482422

Expression profiles

Bgee: expression breadth ubiquitous, 220 present calls, max score 98.06.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 49.1010 / max 2076.3339, expressed in 1478 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
23994	29.5747	1413
23995	6.6377	1179
24001	3.7528	322
23992	1.9308	204
24003	1.3264	260
23998	1.0635	362
24000	1.0398	241
23996	0.7504	353
23990	0.7146	204
23991	0.5569	126

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.06	gold quality
mononuclear cell	CL:0000842	98.01	gold quality
leukocyte	CL:0000738	97.86	gold quality
bone marrow cell	CL:0002092	96.88	gold quality
bone marrow	UBERON:0002371	94.64	gold quality
granulocyte	CL:0000094	94.25	gold quality
vermiform appendix	UBERON:0001154	93.59	gold quality
blood	UBERON:0000178	91.08	gold quality
lymph node	UBERON:0000029	90.91	gold quality
spleen	UBERON:0002106	90.91	gold quality
trabecular bone tissue	UBERON:0002483	90.39	gold quality
secondary oocyte	CL:0000655	89.14	gold quality
colonic epithelium	UBERON:0000397	88.93	gold quality
stromal cell of endometrium	CL:0002255	88.57	gold quality
caecum	UBERON:0001153	87.67	gold quality
rectum	UBERON:0001052	87.30	gold quality
superficial temporal artery	UBERON:0001614	87.25	gold quality
epithelium of nasopharynx	UBERON:0001951	86.90	gold quality
nasopharynx	UBERON:0001728	86.89	gold quality
gall bladder	UBERON:0002110	85.69	gold quality
thymus	UBERON:0002370	85.66	gold quality
tonsil	UBERON:0002372	84.13	gold quality
oocyte	CL:0000023	82.42	gold quality
jejunal mucosa	UBERON:0000399	81.73	gold quality
right lung	UBERON:0002167	81.29	gold quality
small intestine Peyer’s patch	UBERON:0003454	81.01	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.66	gold quality
upper lobe of left lung	UBERON:0008952	80.63	gold quality
mucosa of paranasal sinus	UBERON:0005030	80.42	silver quality
lung	UBERON:0002048	80.21	gold quality

Single-cell (SCXA)

Detected in 11 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	789.82
E-GEOD-130473	yes	522.69
E-GEOD-135922	yes	24.31
E-CURD-122	yes	22.84
E-ANND-3	yes	12.25
E-MTAB-9067	yes	11.27
E-MTAB-6701	yes	11.16
E-MTAB-10042	yes	9.50
E-HCAD-10	yes	7.65
E-MTAB-7381	no	533.67
E-MTAB-6142	no	90.05

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ETS1, ID1, ITGB8, MITF, PAX6, RUNX3, WT1

miRNA regulators (miRDB)

207 targeting ITGA4, 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-4768-5P	100.00	69.49	2861
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979

Literature-anchored findings (GeneRIF, showing 40)

• Alpha 4 integrin signaling activates phosphatidylinositol 3-kinase, stimulates beta 2 integrin-mediated T cell adhesion to ICAM-1, and induces a distinct rearrangement of the actin cytoskeleton. (PMID:11777963)
• role in mediating adhesion and migration of activated cycling CD34+ hematopoietic progenitor cells onto fibronectin (PMID:11877275)
• Human mast cell progenitors use alpha4-integrin, VCAM-1, and PSGL-1, E-selectin for adhesive interactions with human vascular endothelium under flow conditions. (PMID:11929779)
• important for migration of chronic lymphocytic leukemia cells into lymph nodes (PMID:11929789)
• Adhesion to fibronectin via alpha4 integrin (CD49d) protects B cells from apoptosis induced by serum deprivation (PMID:11966761)
• mediates adhesion of osteosarcoma to the core region of thrombospondin 1 (alpha 4 beta 1 integrin) (PMID:12054567)
• VCAM-1/alpha4 integrin (CD49D antigen) interactions mediate monocyte adhesion to human saphenous vein (PMID:12097820)
• VLA4 integrin activation by chemokines requires cholesterol (PMID:12163503)
• role of Rap1 GTPase for Mn(2+)- and antibody-induced VLA-4-mediated cell adhesion [VLA-4] (PMID:12171996)
• regulation of alpha4beta1 integrin function in melanoma cells and T cells by ligands of CD47 (PMID:12218055)
• cell surface alpha4 integrin is downregulated by p38 MAP kinase to facilitate erbB-2-mediated invasion (PMID:12659685)
• 3 new “silent’ ITGA4 variants: a C–>A transversion at 269 in the promoter region of exon 1; a G–>A transversion at 2273 in exon 16, & a T–>C exchange at 3311 in exon 26 are described. The frequencies of all 5 known variants were measured. (PMID:12686501)
• endometrial integrin alpha1 and alpha4 expression is more consistently present in the early luteal phase in stimulated cycles than in natural cycles (PMID:12694973)
• Association of integrin alpha 4 with paxillin mediates cross-talk by enhancing the activation of the related tyrosine kinases FAK and Pyk2 in Jurkat T cells. (PMID:12794117)
• Requires integrin alpha4beta1 to control T cell migration and requires both phosphorylation and dephosphorylation of the alpha 4 cytoplasmic domain to regulate the reversible binding of paxillin. (PMID:12837751)
• Alpha4beta1 integrin has a role in cell adhesion (PMID:12844491)
• in beta-thalassemic patients, significant reduction of CD49d, CD29 and CD71 antigen expression was found in peripheral blood nucleated red cells (PMID:12904899)
• following priming of human neutrophils with lipopolysaccharide or tumor necrosis factor alpha (TNF-alpha), addition of formyl-Met-Leu-Phe (fMLP) results in a “stimulated”, sepsis-like, four- to fivefold rise in CD49d expression (PMID:14525968)
• integrin alpha4beta1 is induced by p53 and has a role in B-cell chronic lymphocytic leukemia drug resistance (PMID:14623330)
• cellular alpha4-integrin is conformationally activated (PMID:14645084)
• integrin alpha-4 has a role in redox regulation of surface protein thiols (PMID:14657342)
• alpha3beta1, alpha4beta1 and alphaVbeta1 integrins may play an important role in the implantation process (PMID:14666169)
• Alpha4beta1 is an important endothelial cell receptor for mediating motility and proliferative responses to thrombospondins and for modulation of angiogenesis. (PMID:14699013)
• Role of alpha4, alpha5, and alphav integrin receptors–which are central to mediating interactions with these domains of FN–in regulating ssquamous cell carcinoma migration. (PMID:15051489)
• EWI-2-dependent reorganization of alpha4beta1-CD81 complexes on the cell surface is responsible for EWI-2 effects on integrin-dependent morphology and motility functions (PMID:15070678)
• findings identify Glu-Pg as an adhesive ligand for integrins alphaMbeta2 and alpha5beta1 and suggest that alpha5beta1 may participate in the binding of soluble Glu-Pg and assist in its activation. (PMID:15090462)
• conformational activation of VLA-4 by inside-out signaling is independent of and additive to reduction-regulated integrin activation (PMID:15166232)
• very late antigen-4 affinity is modulated by shear (PMID:15226304)
• regulatory role of alpha 4 integrins on T lymphocyte-antigen presenting cell cognate immune interactions (PMID:15263094)
• alpha4beta1 integrin on sickle reticulocytes is a CD47-activated receptor for TSP, VCAM-1, and plasma fibronectin (PMID:15292185)
• Cell adhesion to VCAM-1 mediated by very late antigen 4 was suppressed by monoclonal antibodies, dependent on reaction oxygen species. (PMID:15308572)
• metal ion binding sites in the I-like domain and the interface with the hybrid domain are important for rolling and firm adhesion by integrin alpha4beta7 (PMID:15448154)
• demonstrates a cooperative role between alpha5beta1 and alpha4beta1 integrins and suggests that interactions between the Hep II domain and alpha4beta1 integrin could modulate the strength of cytoskeleton-mediated processes in the trabecular meshwork (PMID:15572366)
• Acute myeloid leukemia cells might adhere to and get through vascular endothelium by CD49d/VCAM-1 and CD11a/ICAM-1 adhesion mechanism. (PMID:15622747)
• VEGF and alpha4beta1 integrin have roles in chemokine-induced motility on and through endothelium in chronic lymphocytic leukemia cells but not in normal B lymphocytes (PMID:15731179)
• analyzed the rotavirus-specific VH and VL repertoire in IgD- B cells expressing the intestinal homing marker alpha4beta7 (PMID:15749880)
• activation of Vav1-Rac signaling pathway by CXCL12 represents an important inside-out event controlling efficient up-regulation of alpha4beta1-dependent T lymphocyte adhesion (PMID:15872091)
• ITGA4 mediates engraftment of GCSF-mobilized stem cells. (PMID:15987366)
• CD44 and CD49d are putative activity markers and CD44 a potential novel therapeutic target in multiple sclerosis. (PMID:15990174)
• These data suggest that during a respiratory virus infection activated CD8+ T cells from asthmatic subjects may produce excess type 2 cytokines and may contribute to asthma exacerbation by augmenting allergic inflammation. (PMID:16001979)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	itga4	ENSDARG00000103056
mus_musculus	Itga4	ENSMUSG00000027009
rattus_norvegicus	Itga4	ENSRNOG00000004861
drosophila_melanogaster	if	FBGN0001250
drosophila_melanogaster	ItgaPS4	FBGN0034005
drosophila_melanogaster	ItgaPS5	FBGN0034880
drosophila_melanogaster	scb	FBGN0286785
caenorhabditis_elegans		WBGENE00003929

Paralogs (17): ITGAL (ENSG00000005844), ITGA3 (ENSG00000005884), ITGA2B (ENSG00000005961), ITGA8 (ENSG00000077943), ITGAE (ENSG00000083457), ITGA6 (ENSG00000091409), ITGA7 (ENSG00000135424), ITGA11 (ENSG00000137809), ITGAV (ENSG00000138448), ITGAX (ENSG00000140678), ITGA10 (ENSG00000143127), ITGA9 (ENSG00000144668), ITGAD (ENSG00000156886), ITGA5 (ENSG00000161638), ITGA2 (ENSG00000164171), ITGAM (ENSG00000169896), ITGA1 (ENSG00000213949)

Protein

Protein identifiers

Integrin alpha-4 — P13612 (reviewed: P13612)

Alternative names: CD49 antigen-like family member D, Integrin alpha-IV, VLA-4 subunit alpha

All UniProt accessions (2): P13612, E7EP60

UniProt curated annotations — full annotation on UniProt →

Function. Integrins alpha-4/beta-1 (VLA-4) and alpha-4/beta-7 are receptors for fibronectin. They recognize one or more domains within the alternatively spliced CS-1 and CS-5 regions of fibronectin. They are also receptors for VCAM1. Integrin alpha-4/beta-1 recognizes the sequence Q-I-D-S in VCAM1. Integrin alpha-4/beta-7 is also a receptor for MADCAM1. It recognizes the sequence L-D-T in MADCAM1. On activated endothelial cells integrin VLA-4 triggers homotypic aggregation for most VLA-4-positive leukocyte cell lines. It may also participate in cytolytic T-cell interactions with target cells. ITGA4:ITGB1 binds to fractalkine (CX3CL1) and may act as its coreceptor in CX3CR1-dependent fractalkine signaling. ITGA4:ITGB1 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. Integrin ITGA4:ITGB1 represses PRKCA-mediated L-type voltage-gated channel Ca(2+) influx and ROCK-mediated calcium sensitivity in vascular smooth muscle cells via its interaction with SVEP1, thereby inhibiting vasocontraction.

Subunit / interactions. Heterodimer of an alpha and a beta subunit. The alpha subunit can sometimes be cleaved into two non-covalently associated fragments. Alpha-4 associates with either beta-1 or beta-7. Alpha-4 interacts with PXN, LPXN, and TGFB1I1/HIC5. Interacts with CSPG4 through CSPG4 chondroitin sulfate glycosaminoglycan. Interacts with JAML; integrin alpha-4/beta-1 may regulate leukocyte to endothelial cells adhesion by controlling JAML homodimerization. ITGA4:ITGB1 is found in a ternary complex with CX3CR1 and CX3CL1. Interacts with MDK. ITGA4:ITGB1 interacts with MDK; this interaction mediates MDK-induced osteoblast cells migration through PXN phosphorylation. Integrin ITGA4:ITGB1 interacts with SVEP1 (via Sushi domain 21); thereby inhibits Ca(2+) intracellular signaling and as a result represses vasocontraction. ITGA4:ITGB1 interacts with SELP. ITGA4:ITGB1 interacts with BCAM.

Subcellular location. Membrane.

Tissue specificity. Expressed in vascular smooth muscle cells (at protein level).

Post-translational modifications. Phosphorylation on Ser-1027 inhibits PXN binding.

Domain organisation. The SG1 motif is involved in binding to chondroitin sulfate glycosaminoglycan and cell adhesion.

Similarity. Belongs to the integrin alpha chain family.

Isoforms (2)

UniProt ID	Names	Canonical?
P13612-1	1	yes
P13612-2	2

RefSeq proteins (2): NP_000876, NP_001303241 (=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: PF01839, PF08441, PF20805, PF20806

UniProt features (111 total): strand 41, binding site 13, glycosylation site 11, disulfide bond 9, repeat 7, mutagenesis site 7, helix 6, sequence variant 3, turn 3, short sequence motif 2, topological domain 2, splice variant 2, signal peptide 1, chain 1, site 1, modified residue 1, transmembrane region 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
4HKC	X-RAY DIFFRACTION	2.2
5C7Z	X-RAY DIFFRACTION	2.77
5FPI	X-RAY DIFFRACTION	2.77
9P95	ELECTRON MICROSCOPY	3.05
3V4V	X-RAY DIFFRACTION	3.1
9P96	ELECTRON MICROSCOPY	3.1
3V4P	X-RAY DIFFRACTION	3.15

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P13612-F1	84.11	0.50

Antibody-complex structures (SAbDab): 2 — 3V4P, 3V4V

Functional residue map

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

Catalytic / active sites (1): 591–592 (cleavage)

Ligand- & substrate-binding residues (13): 314; 316; 318; 322; 377; 379; 381; 385; 439; 441; 443; 445 …

Post-translational modifications (1): 1021

Disulfide bonds (9): 91–101, 144–165, 183–198, 486–495, 501–557, 622–627, 698–711, 852–890, 897–902

Glycosylation sites (11): 79, 138, 229, 480, 518, 538, 626, 645, 660, 806, 821

Mutagenesis-validated functional residues (7):

Position	Phenotype
222	blocks binding to pla2g2a.
223	blocks binding to pla2g2a.
590	abolishes almost completely cleavage.
591	abolishes completely cleavage.
1021	abolishes phosphorylation.
1021	reduces pxn binding.
1024	disrupts pxn binding.

Function

Pathways and Gene Ontology

Reactome pathways

17 pathways

ID	Pathway
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-216083	Integrin cell surface interactions
R-HSA-8949275	RUNX3 Regulates Immune Response and Cell Migration
R-HSA-9679191	Potential therapeutics for SARS
R-HSA-109582	Hemostasis
R-HSA-1280218	Adaptive Immune System
R-HSA-1474244	Extracellular matrix organization
R-HSA-1643685	Disease
R-HSA-168256	Immune System
R-HSA-212436	Generic Transcription Pathway
R-HSA-5663205	Infectious disease
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8878159	Transcriptional regulation by RUNX3
R-HSA-9679506	SARS-CoV Infections
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 569 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, ZHAN_LATE_DIFFERENTIATION_GENES_UP, WALLACE_PROSTATE_CANCER_RACE_UP, BENPORATH_ES_WITH_H3K27ME3, MODULE_169, GOBP_NEURON_PROJECTION_EXTENSION, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_VESICLE_LOCALIZATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, MODULE_255, GOBP_RESPONSE_TO_PEPTIDE, GOBP_B_CELL_ACTIVATION, GOBP_FORMATION_OF_PRIMARY_GERM_LAYER, GOBP_POSITIVE_REGULATION_OF_LYMPHOCYTE_MIGRATION, GOBP_GROWTH

GO Biological Process (32): immune response in gut-associated lymphoid tissue (GO:0002387), cell-matrix adhesion involved in ameboidal cell migration (GO:0003366), leukocyte cell-cell adhesion (GO:0007159), cell-matrix adhesion (GO:0007160), integrin-mediated signaling pathway (GO:0007229), B cell differentiation (GO:0030183), cell-cell adhesion mediated by integrin (GO:0033631), heterotypic cell-cell adhesion (GO:0034113), substrate adhesion-dependent cell spreading (GO:0034446), endodermal cell differentiation (GO:0035987), receptor clustering (GO:0043113), negative regulation of vasoconstriction (GO:0045906), leukocyte tethering or rolling (GO:0050901), diapedesis (GO:0050904), axonogenesis involved in innervation (GO:0060385), cellular response to cytokine stimulus (GO:0071345), obsolete negative regulation of protein homodimerization activity (GO:0090074), cell-cell adhesion (GO:0098609), positive regulation of leukocyte tethering or rolling (GO:1903238), cellular response to amyloid-beta (GO:1904646), positive regulation of vascular endothelial cell proliferation (GO:1905564), neuron projection extension (GO:1990138), clathrin-dependent extracellular exosome endocytosis (GO:1990771), positive regulation of endothelial cell apoptotic process (GO:2000353), positive regulation of T cell migration (GO:2000406), positive regulation of leukocyte migration (GO:0002687), cell adhesion (GO:0007155), tissue development (GO:0009888), embryonic morphogenesis (GO:0048598), leukocyte migration (GO:0050900), import into cell (GO:0098657), positive regulation of leukocyte cell-cell adhesion (GO:1903039)

GO Molecular Function (10): fibronectin binding (GO:0001968), integrin binding (GO:0005178), coreceptor activity (GO:0015026), signaling receptor activity (GO:0038023), metal ion binding (GO:0046872), cell adhesion molecule binding (GO:0050839), protein antigen binding (GO:1990405), antigen binding (GO:0003823), protein binding (GO:0005515), C-X3-C chemokine binding (GO:0019960)

GO Cellular Component (10): plasma membrane (GO:0005886), focal adhesion (GO:0005925), cell surface (GO:0009986), membrane (GO:0016020), growth cone (GO:0030426), integrin alpha4-beta1 complex (GO:0034668), integrin alpha4-beta7 complex (GO:0034669), neuronal cell body (GO:0043025), extracellular exosome (GO:0070062), integrin complex (GO:0008305)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Adaptive Immune System	1
Hemostasis	1
Extracellular matrix organization	1
Transcriptional regulation by RUNX3	1
SARS-CoV Infections	1
Immune System	1
RNA Polymerase II Transcription	1
Disease	1
Gene expression (Transcription)	1
Generic Transcription Pathway	1
Viral Infection Pathways	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell-cell adhesion	3
protein binding	3
cell-substrate adhesion	2
cellular extravasation	2
binding	2
cellular anatomical structure	2
integrin complex	2
immune response	1
ameboidal-type cell migration	1
cell-matrix adhesion	1
cell surface receptor signaling pathway	1
lymphocyte differentiation	1
B cell activation	1
cell adhesion mediated by integrin	1
endoderm formation	1
cell differentiation	1
plasma membrane	1
protein localization to membrane	1
regulation of vasoconstriction	1
vasoconstriction	1
negative regulation of multicellular organismal process	1
leukocyte adhesion to vascular endothelial cell	1
leukocyte migration	1
axonogenesis	1
innervation	1
response to cytokine	1
cell adhesion	1
leukocyte tethering or rolling	1
regulation of leukocyte tethering or rolling	1
positive regulation of leukocyte adhesion to vascular endothelial cell	1
cellular response to nitrogen compound	1
cellular response to oxygen-containing compound	1
response to amyloid-beta	1
signaling receptor binding	1
protein-containing complex binding	1
cell adhesion molecule binding	1
signaling receptor activity	1
molecular transducer activity	1
cation binding	1
antigen binding	1

Protein interactions and networks

STRING

2422 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ITGA4	ITGB1	P05556	998
ITGA4	VCAM1	P19320	997
ITGA4	ITGB7	P26010	996
ITGA4	FN1	P02751	995
ITGA4	PXN	P49023	986
ITGA4	ICAM1	P05362	985
ITGA4	TSPAN8	P19075	985
ITGA4	MADCAM1	Q13477	980
ITGA4	ITGB2	P05107	928
ITGA4	CD44	P16070	902
ITGA4	ITGB3	P05106	852
ITGA4	CD8A	P01732	819
ITGA4	SELL	P14151	819
ITGA4	CCR7	P32248	809
ITGA4	CD28	P10747	766

IntAct

92 interactions, top by confidence:

A	B	Type	Score
FN1	ITGB1	psi-mi:“MI:0915”(physical association)	0.750
FN1	ITGB3	psi-mi:“MI:0915”(physical association)	0.750
ITGA4	ITGB7	psi-mi:“MI:0407”(direct interaction)	0.740
ITGA4	ITGB7	psi-mi:“MI:0915”(physical association)	0.740
ITGA4	PXN	psi-mi:“MI:0915”(physical association)	0.690
PXN	ITGA4	psi-mi:“MI:0915”(physical association)	0.690
ITGA4	ITGB1	psi-mi:“MI:0915”(physical association)	0.680
ITGB1	ITGA4	psi-mi:“MI:0915”(physical association)	0.680
KCNJ2	KCNJ18	psi-mi:“MI:2364”(proximity)	0.660
VCAM1	ITGB1	psi-mi:“MI:0914”(association)	0.660
Ap2m1	ITGA4	psi-mi:“MI:0407”(direct interaction)	0.560
ITGA4	ABI1	psi-mi:“MI:0915”(physical association)	0.540
ITGA4	ABI1	psi-mi:“MI:0407”(direct interaction)	0.540
TAFA4	NRP1	psi-mi:“MI:0914”(association)	0.530
CST9	ITGA4	psi-mi:“MI:0914”(association)	0.530
PICK1	ILVBL	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
LGALS1	PODXL	psi-mi:“MI:0914”(association)	0.530
VCAM1	PSMD11	psi-mi:“MI:0914”(association)	0.530
ITGB1	LYN	psi-mi:“MI:0914”(association)	0.430
LYN	ITGB1	psi-mi:“MI:0914”(association)	0.430
ITGA4	LYN	psi-mi:“MI:0403”(colocalization)	0.430
Itgb1	FN1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (575): ITGA4 (Affinity Capture-MS), ITGA4 (Affinity Capture-MS), ITGA4 (Affinity Capture-MS), ITGA4 (Affinity Capture-MS), ITGA4 (Affinity Capture-MS), ITGA4 (Affinity Capture-MS), ITGA4 (Affinity Capture-MS), ITGA4 (Affinity Capture-MS), EED (Two-hybrid), ITGA4 (Affinity Capture-MS), ITGA4 (Affinity Capture-MS), ITGA4 (Affinity Capture-MS), ITGA4 (Affinity Capture-MS), ITGA4 (Affinity Capture-MS), ITGA4 (Affinity Capture-MS)

ESM2 similar proteins: A2ARA8, B0S5N4, B8JK39, F1MMS9, O08665, P05555, P06756, P08514, P08648, P11215, P11688, P13612, P17301, P17852, P18564, P20701, P23229, P24063, P26006, P26007, P26008, P26009, P38570, P43406, P53708, P53710, P53711, P61622, P61625, P80746, Q00651, Q06274, Q13683, Q13797, Q60677, Q61738, Q61739, Q62469, Q62470, Q63258

Diamond homologs: B8JK39, O70362, P13612, P20701, P24063, P26008, P61625, Q00651, Q13797, Q91687, P80109, F1MMS9, P05555, P17852, P23229, P26006, P26007, P80108, Q13683, Q24247, Q61738, Q61739, Q62470, Q63258, Q8R2H5, Q86AV9, A2ARA8, O44386, P26009, P47014, Q03600, Q9V7A4

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
PRKACA	“up-regulates activity”	ITGA4	phosphorylation
ITGA4	“form complex”	“A4/b1 integrin”	binding
ITGA4	“form complex”	“A4/b7 integrin”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 72 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
Integrin cell surface interactions	7	21.9×	1e-05
Cell surface interactions at the vascular wall	6	13.3×	7e-04

GO biological processes:

GO term	Partners	Fold	FDR
substrate adhesion-dependent cell spreading	5	27.7×	2e-04
cell-matrix adhesion	6	15.8×	4e-04
integrin-mediated signaling pathway	5	12.9×	2e-03
cell adhesion	14	8.5×	5e-07
positive regulation of ERK1 and ERK2 cascade	6	8.2×	3e-03
cell-cell adhesion	5	8.2×	7e-03
cell migration	7	6.9×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	119
Likely benign	17
Benign	12

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1526933	GRCh37/hg19 2q31.1-35(chr2:169829974-215521436)	Pathogenic
986978	NM_000885.6(ITGA4):c.*2719T>C	Likely pathogenic

SpliceAI

3640 predictions. Top by Δscore:

Variant	Effect	Δscore
2:181457848:GATG:G	donor_gain	1.0000
2:181458313:GCTGG:G	donor_gain	1.0000
2:181478751:TTTTA:T	acceptor_loss	1.0000
2:181478752:TTTA:T	acceptor_loss	1.0000
2:181478753:TTAGA:T	acceptor_loss	1.0000
2:181478754:TAG:T	acceptor_loss	1.0000
2:181478755:A:AG	acceptor_gain	1.0000
2:181478755:A:C	acceptor_loss	1.0000
2:181478756:G:GC	acceptor_gain	1.0000
2:181478756:GA:G	acceptor_gain	1.0000
2:181478756:GATT:G	acceptor_gain	1.0000
2:181478756:GATTA:G	acceptor_gain	1.0000
2:181478821:AAAG:A	donor_loss	1.0000
2:181478824:GGTAA:G	donor_loss	1.0000
2:181478825:G:A	donor_loss	1.0000
2:181478826:T:A	donor_loss	1.0000
2:181481594:A:AG	acceptor_gain	1.0000
2:181481594:AAAG:A	acceptor_gain	1.0000
2:181481595:A:G	acceptor_gain	1.0000
2:181481595:AAG:A	acceptor_gain	1.0000
2:181481596:A:AG	acceptor_gain	1.0000
2:181481596:A:AT	acceptor_loss	1.0000
2:181481596:AG:A	acceptor_gain	1.0000
2:181481597:G:A	acceptor_gain	1.0000
2:181481597:G:GT	acceptor_gain	1.0000
2:181481597:GGA:G	acceptor_gain	1.0000
2:181481597:GGAT:G	acceptor_gain	1.0000
2:181481597:GGATA:G	acceptor_gain	1.0000
2:181481674:GATTG:G	donor_gain	1.0000
2:181481679:GTAAG:G	donor_gain	1.0000

AlphaMissense

6823 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:181478792:T:C	C198R	0.999
2:181478793:G:A	C198Y	0.999
2:181478794:T:G	C198W	0.999
2:181480152:G:T	G214W	0.999
2:181458254:G:T	G86W	0.998
2:181475018:G:C	W126C	0.998
2:181475018:G:T	W126C	0.998
2:181475162:T:C	C144R	0.998
2:181475163:G:A	C144Y	0.998
2:181475164:T:G	C144W	0.998
2:181475279:T:C	C183R	0.998
2:181475280:G:A	C183Y	0.998
2:181475281:T:G	C183W	0.998
2:181480152:G:A	G214R	0.998
2:181480152:G:C	G214R	0.998
2:181480173:T:A	W221R	0.998
2:181480173:T:C	W221R	0.998
2:181480179:G:T	G223C	0.998
2:181480180:G:A	G223D	0.998
2:181480180:G:T	G223V	0.998
2:181481598:G:A	G252E	0.998
2:181481679:G:A	G279D	0.998
2:181482578:T:C	L323P	0.998
2:181457812:G:A	G53D	0.997
2:181458213:C:A	P72H	0.997
2:181458269:T:A	C91S	0.997
2:181458270:G:C	C91S	0.997
2:181474994:T:G	C118W	0.997
2:181475016:T:A	W126R	0.997
2:181475016:T:C	W126R	0.997

dbSNP variants (sampled 300 via entrez): RS1000011736 (2:181492290 A>T), RS1000018859 (2:181456714 G>A), RS1000050357 (2:181510988 A>G), RS1000066339 (2:181538952 C>CTCTT), RS1000213075 (2:181513504 A>C,G), RS1000254615 (2:181472434 A>G), RS1000311581 (2:181466630 A>G,T), RS1000315925 (2:181480924 C>A), RS1000341904 (2:181466935 G>A,C), RS1000426093 (2:181516429 T>G), RS1000489467 (2:181534423 A>G), RS1000526852 (2:181518514 G>A), RS1000528015 (2:181530243 T>C), RS1000543951 (2:181511596 A>G), RS1000548819 (2:181512110 G>A,T)

Disease associations

OMIM: gene MIM:192975 | disease phenotypes: MIM:268000, MIM:608380

GenCC curated gene-disease

Mondo (2): retinitis pigmentosa (MONDO:0019200), retinitis pigmentosa 26 (MONDO:0012024)

Orphanet (1): Retinitis pigmentosa (Orphanet:791)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

47 associations (top):

Study	Trait	p-value
GCST000612_2	Celiac disease	5.000000e-11
GCST001134_17	White blood cell types	2.000000e-14
GCST001137_4	White blood cell count	3.000000e-23
GCST001887_1	Monocyte count	5.000000e-17
GCST002555_4	Monocyte count	7.000000e-14
GCST002555_5	Monocyte count	8.000000e-08
GCST002594_24	Neurofibrillary tangles	6.000000e-06
GCST003265_323	Post bronchodilator FEV1/FVC ratio in COPD	5.000000e-06
GCST004129_1	White blood cell count (monocyte)	8.000000e-20
GCST004131_2	Inflammatory bowel disease	1.000000e-13
GCST004132_67	Crohn’s disease	1.000000e-10
GCST004133_34	Ulcerative colitis	1.000000e-06
GCST004164_2	Monocyte count	2.000000e-07
GCST004170_1	Monocyte-lymphocyte ratio	2.000000e-08
GCST004608_62	Granulocyte percentage of myeloid white cells	2.000000e-151
GCST004609_150	Monocyte percentage of white cells	1.000000e-222
GCST004611_17	High light scatter reticulocyte count	1.000000e-12
GCST004612_52	High light scatter reticulocyte percentage of red cells	3.000000e-13
GCST004625_55	Monocyte count	6.000000e-281
GCST004625_56	Monocyte count	4.000000e-10
GCST004628_150	Immature fraction of reticulocytes	1.000000e-31
GCST004632_136	Lymphocyte percentage of white cells	1.000000e-10
GCST005523_9	Celiac disease	3.000000e-16
GCST005531_88	Multiple sclerosis	2.000000e-06
GCST005973_23	White blood cell count	3.000000e-08
GCST005976_2	White blood cell count (basophil)	4.000000e-08
GCST005977_28	Monocyte count	8.000000e-63
GCST009873_9	Autoimmune traits (pleiotropy)	1.000000e-18
GCST010002_406	Refractive error	3.000000e-08
GCST010572_11	Sweet taste preference	5.000000e-06

EFO canonical traits (14, from GWAS)

EFO ID	Trait name
EFO:0005091	monocyte count
EFO:0006797	neurofibrillary tangles measurement
EFO:0004713	FEV/FVC ratio
EFO:0007956	monocyte:lymphocyte ratio
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0007986	reticulocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0005090	basophil count
EFO:0010156	sweet liking measurement
EFO:0010701	mean reticulocyte volume
EFO:0004833	neutrophil count
EFO:0007990	neutrophil percentage of leukocytes
EFO:0004533	alkaline phosphatase measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
C564249	Retinitis Pigmentosa 26 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL1907599 (PROTEIN COMPLEX), CHEMBL2095184 (PROTEIN COMPLEX), CHEMBL278 (SINGLE PROTEIN)

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 (1 total), top 1:

Ligand	Action	Affinity	Parameter
abrilumab	Inhibition	11.05	pKd

Binding affinities (BindingDB)

1163 measured of 1836 human assays (1849 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(5S)-5-[(1-carbamoylcyclohexyl)carbamoyl]-5-[(2S)-2-[1-(4-{[(2-methylphenyl)carbamoyl]amino}phenyl)acetamido]-6-[(2E)-3-(pyridin-3-yl)prop-2-enamido]hexanamido]pentanoic acid	IC50	0.0372 nM
(2S)-2-[[2-chloro-6-fluoro-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]-3-[8-(1-methyl-2,4-dioxopyrido[3,4-d]pyrimidin-3-yl)quinolin-5-yl]propanoic acid	EC50	0.048 nM	US-11116760: Quinoline derivatives
(2S)-2-[[2-fluoro-6-methyl-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]-3-[8-(1-methyl-2,4-dioxopyrido[3,4-d]pyrimidin-3-yl)quinolin-5-yl]propanoic acid	EC50	0.049 nM	US-11116760: Quinoline derivatives
(2S)-2-[[2-fluoro-6-methyl-4-[[(2R)-1,1,1-trifluorobutan-2-yl]amino]benzoyl]amino]-3-[8-(1-methyl-2,4-dioxopyrido[3,4-d]pyrimidin-3-yl)quinolin-5-yl]propanoic acid	EC50	0.049 nM	US-11116760: Quinoline derivatives
(2S)-2-[[2-fluoro-6-methyl-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]-3-[8-(1-methyl-2,4-dioxopyrido[3,4-d]pyrimidin-3-yl)quinolin-5-yl]propanoic acid	EC50	0.05 nM	US-11116760: Quinoline derivatives
(2S)-3-[8-(2,4-dimethyl-5,7-dioxo-[1,3]thiazolo[4,5-d]pyrimidin-6-yl)quinolin-5-yl]-2-[[2-fluoro-6-methyl-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]propanoic acid	EC50	0.054 nM	US-11116760: Quinoline derivatives
(2S)-2-[[2-fluoro-6-methyl-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]-3-[8-(1-methyl-2,4-dioxo-6,8-dihydro-5H-pyrano[3,4-d]pyrimidin-3-yl)quinolin-5-yl]propanoic acid	EC50	0.06 nM	US-11116760: Quinoline derivatives
(2S)-3-[7-fluoro-8-(1-methyl-2,4-dioxopyrido[3,4-d]pyrimidin-3-yl)quinolin-5-yl]-2-[[2-fluoro-6-methyl-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]propanoic acid	EC50	0.076 nM	US-11116760: Quinoline derivatives
(2S)-3-[8-(1-methyl-2,4-dioxopyrido[3,4-d]pyrimidin-3-yl)quinolin-5-yl]-2-[[2,3,6-trifluoro-4-[[(2R)-1,1,1-trifluorobutan-2-yl]amino]benzoyl]amino]propanoic acid	EC50	0.076 nM	US-11116760: Quinoline derivatives
(2S)-2-[[2-fluoro-6-methyl-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]-3-[8-(1-methyl-2,4-dioxopyrimido[4,5-d]pyrimidin-3-yl)quinolin-5-yl]propanoic acid	EC50	0.08 nM	US-11116760: Quinoline derivatives
(2S)-2-[[2,6-difluoro-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]-3-[8-(7-fluoro-1-methyl-2,4-dioxoquinazolin-3-yl)quinolin-5-yl]propanoic acid	EC50	0.08 nM	US-11116760: Quinoline derivatives
(2S)-3-[8-[1,2-dimethyl-6-oxo-4-(trifluoromethyl)pyrimidin-5-yl]quinolin-5-yl]-2-[[2-fluoro-6-methyl-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]propanoic acid	EC50	0.09 nM	US-11116760: Quinoline derivatives
(2S)-2-[[2-fluoro-6-methyl-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]-3-[8-(1-methyl-2,4-dioxo-7,8-dihydro-5H-pyrano[4,3-d]pyrimidin-3-yl)quinolin-5-yl]propanoic acid	EC50	0.091 nM	US-11116760: Quinoline derivatives
(2S)-2-[[2-fluoro-6-methyl-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]-3-[8-(7-methoxy-1-methyl-2,4-dioxopyrido[3,2-d]pyrimidin-3-yl)quinolin-5-yl]propanoic acid	EC50	0.091 nM	US-11116760: Quinoline derivatives
(2S)-3-[8-(4-chloro-1,6-dimethyl-2-oxo-3-pyridinyl)quinolin-5-yl]-2-[[2-fluoro-6-methyl-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]propanoic acid	EC50	0.092 nM	US-11116760: Quinoline derivatives
(2S)-3-[8-[1,6-dimethyl-2-oxo-4-(trifluoromethyl)-3-pyridinyl]quinolin-5-yl]-2-[[2-fluoro-6-methyl-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]propanoic acid	EC50	0.093 nM	US-11116760: Quinoline derivatives
(2S)-3-[8-(7-fluoro-1-methyl-2,4-dioxoquinazolin-3-yl)quinolin-5-yl]-2-[[2-fluoro-6-methyl-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]propanoic acid	EC50	0.094 nM	US-11116760: Quinoline derivatives
(2S)-3-[3-fluoro-8-(1-methyl-2,4-dioxopyrido[3,4-d]pyrimidin-3-yl)quinolin-5-yl]-2-[[2-fluoro-6-methyl-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]propanoic acid	EC50	0.096 nM	US-11116760: Quinoline derivatives
(2S)-2-[[2,6-difluoro-4-[[(2R)-1,1,1-trifluorobutan-2-yl]amino]benzoyl]amino]-3-[8-[1-methyl-2-oxo-4-(trifluoromethyl)-1,7-naphthyridin-3-yl]quinolin-5-yl]propanoic acid	EC50	0.1 nM	US-11116760: Quinoline derivatives
(2S)-3-[8-[1,6-dimethyl-2-oxo-4-(trifluoromethyl)-3-pyridinyl]quinolin-5-yl]-2-[[2-fluoro-6-methyl-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]propanoic acid	EC50	0.1 nM	US-11116760: Quinoline derivatives
(2S)-2-[[2-fluoro-6-methyl-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]-3-[8-(1-methyl-2,4-dioxopyrido[3,2-d]pyrimidin-3-yl)quinolin-5-yl]propanoic acid	EC50	0.1 nM	US-11116760: Quinoline derivatives
(2S)-2-[[2-fluoro-6-methyl-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]-3-[8-(1-methyl-2,4-dioxopyrido[4,3-d]pyrimidin-3-yl)quinolin-5-yl]propanoic acid	EC50	0.1 nM	US-11116760: Quinoline derivatives
(2S)-2-[[2-fluoro-6-methyl-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]-3-[8-(1-methyl-2,4-dioxopyrido[2,3-d]pyrimidin-3-yl)quinolin-5-yl]propanoic acid	EC50	0.1 nM	US-11116760: Quinoline derivatives
(2S)-2-[[2-fluoro-6-methyl-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]-3-[8-(1-methyl-2,4-dioxopteridin-3-yl)quinolin-5-yl]propanoic acid	EC50	0.1 nM	US-11116760: Quinoline derivatives
(2S)-3-[8-[1,6-dimethyl-2-oxo-4-(trifluoromethyl)-3-pyridinyl]quinolin-5-yl]-2-[[2-fluoro-6-(trideuteriomethyl)-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]propanoic acid	EC50	0.102 nM	US-11116760: Quinoline derivatives
(2S)-2-[[2-fluoro-6-methyl-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]-3-[8-(1-methyl-2,4-dioxopyrido[4,3-d]pyrimidin-3-yl)quinolin-5-yl]propanoic acid	EC50	0.103 nM	US-11116760: Quinoline derivatives
(2S)-2-[[2-fluoro-6-methyl-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]-3-[8-(1-methyl-2-oxo-1,6-naphthyridin-3-yl)quinolin-5-yl]propanoic acid	EC50	0.103 nM	US-11116760: Quinoline derivatives
(2S)-3-[8-(6-fluoro-7-imidazol-1-yl-1-methyl-2,4-dioxoquinazolin-3-yl)quinolin-5-yl]-2-[[2-fluoro-6-methyl-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]propanoic acid	EC50	0.104 nM	US-11116760: Quinoline derivatives
(2S)-2-[[2-fluoro-6-methyl-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]-3-[8-(1-methyl-2,4-dioxopyrido[2,3-d]pyrimidin-3-yl)quinolin-5-yl]propanoic acid	EC50	0.11 nM	US-11116760: Quinoline derivatives
(2S)-2-[[2,6-difluoro-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]-3-[8-(1-methyl-2,4-dioxopyrido[3,4-d]pyrimidin-3-yl)quinolin-5-yl]propanoic acid	EC50	0.112 nM	US-11116760: Quinoline derivatives
(2S)-2-[[2-fluoro-6-methyl-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]-3-[8-(4,5,6-trimethyl-3-oxopyrazin-2-yl)quinolin-5-yl]propanoic acid	EC50	0.115 nM	US-11116760: Quinoline derivatives
(2S)-3-[8-(6-fluoro-1-methyl-2,4-dioxopyrido[3,4-d]pyrimidin-3-yl)quinolin-5-yl]-2-[[2-fluoro-6-methyl-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]propanoic acid	EC50	0.116 nM	US-11116760: Quinoline derivatives
(2S)-3-[8-(1-ethyl-2,4-dioxopyrido[3,4-d]pyrimidin-3-yl)quinolin-5-yl]-2-[[2-fluoro-6-methyl-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]propanoic acid	EC50	0.117 nM	US-11116760: Quinoline derivatives
(2S)-3-[8-[6-(dimethylamino)-1-methyl-2,4-dioxopyrido[3,4-d]pyrimidin-3-yl]quinolin-5-yl]-2-[[2-fluoro-6-methyl-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]propanoic acid	EC50	0.126 nM	US-11116760: Quinoline derivatives
(2S)-3-[7-fluoro-8-(1-methyl-2-oxo-1,6-naphthyridin-3-yl)quinolin-5-yl]-2-[[2-fluoro-6-methyl-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]propanoic acid	EC50	0.13 nM	US-11116760: Quinoline derivatives
(2S)-2-[[2-chloro-6-fluoro-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]-3-[8-(4,5,6-trimethyl-3-oxopyrazin-2-yl)quinolin-5-yl]propanoic acid	EC50	0.14 nM	US-11116760: Quinoline derivatives
(2S)-2-[[2,6-difluoro-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]-3-[8-(4-methyl-3-oxoquinoxalin-2-yl)quinolin-5-yl]propanoic acid	EC50	0.143 nM	US-11116760: Quinoline derivatives
(2S)-2-[[2,6-difluoro-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]-3-[8-(1,6-dimethyl-2,4-dioxopyrido[3,4-d]pyrimidin-3-yl)quinolin-5-yl]propanoic acid	EC50	0.15 nM	US-11116760: Quinoline derivatives
(2S)-2-[[2-fluoro-6-methyl-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]-3-[8-(1,2,4-trimethyl-6-oxopyrimidin-5-yl)quinolin-5-yl]propanoic acid	EC50	0.15 nM	US-11116760: Quinoline derivatives
(2S)-2-[[2,6-difluoro-4-[[(2R)-1,1,1-trifluorobutan-2-yl]amino]benzoyl]amino]-3-[8-(1-methyl-2,4-dioxopyrido[3,4-d]pyrimidin-3-yl)quinolin-5-yl]propanoic acid	EC50	0.157 nM	US-11116760: Quinoline derivatives
(2S)-3-[8-(1,6-dimethyl-2-oxo-3-pyridinyl)quinolin-5-yl]-2-[[2-fluoro-6-methyl-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]propanoic acid	EC50	0.161 nM	US-11116760: Quinoline derivatives
(2S)-2-[[2-fluoro-6-methyl-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]-3-[8-(1-methyl-2,4-dioxopyrido[3,4-d]pyrimidin-3-yl)quinolin-5-yl]propanoic acid	EC50	0.162 nM	US-11116760: Quinoline derivatives
(2S)-2-[[2-fluoro-6-methyl-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]-3-[8-(6-methoxy-1-methyl-2,4-dioxopyrido[3,4-d]pyrimidin-3-yl)quinolin-5-yl]propanoic acid	EC50	0.162 nM	US-11116760: Quinoline derivatives
(2S)-3-[8-[1,6-dimethyl-2-oxo-4-(trifluoromethyl)-3-pyridinyl]quinolin-5-yl]-2-[[2-ethyl-6-fluoro-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]propanoic acid	EC50	0.179 nM	US-11116760: Quinoline derivatives
(2S)-2-[[2,6-difluoro-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]-3-[8-(6-methoxy-1-methyl-2,4-dioxopyrido[3,4-d]pyrimidin-3-yl)quinolin-5-yl]propanoic acid	EC50	0.18 nM	US-11116760: Quinoline derivatives
(2S)-3-[8-[1,6-dimethyl-2-oxo-4-(trifluoromethyl)-3-pyridinyl]quinolin-5-yl]-2-[[2-fluoro-6-propan-2-yl-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]propanoic acid	EC50	0.181 nM	US-11116760: Quinoline derivatives
(2S)-3-[8-(1,6-dimethyl-2,4-dioxopyrido[3,4-d]pyrimidin-3-yl)quinolin-5-yl]-2-[[2-fluoro-6-methyl-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]propanoic acid	EC50	0.185 nM	US-11116760: Quinoline derivatives
(2S)-2-[[2,6-difluoro-4-[(2S,3R)-2-methyl-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]-3-[8-[1,6-dimethyl-2-oxo-4-(trifluoromethyl)-3-pyridinyl]quinolin-5-yl]propanoic acid	EC50	0.189 nM	US-11116760: Quinoline derivatives
(2S)-3-[8-(2,4-dioxo-1H-pyrido[3,4-d]pyrimidin-3-yl)quinolin-5-yl]-2-[[2-fluoro-6-methyl-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]propanoic acid	EC50	0.191 nM	US-11116760: Quinoline derivatives
(2S)-2-[[2,6-difluoro-4-[(3R)-3-(trifluoromethyl)morpholin-4-yl]benzoyl]amino]-3-[8-(1-methyl-2,4-dioxopyrido[4,3-d]pyrimidin-3-yl)quinolin-5-yl]propanoic acid	EC50	0.196 nM	US-11116760: Quinoline derivatives

ChEMBL bioactivities

2493 potent at pChembl≥5 of 2607 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.70	IC50	0.02	nM	CHEMBL569442
10.66	IC50	0.022	nM	CHEMBL1241140
10.52	IC50	0.03	nM	CHEMBL296804
10.52	IC50	0.03	nM	CHEMBL566154
10.43	IC50	0.0372	nM	CHEMBL395150
10.43	IC50	0.037	nM	CHEMBL447509
10.30	IC50	0.05	nM	CHEMBL2110195
10.30	IC50	0.05	nM	CHEMBL69035
10.28	IC50	0.0525	nM	CHEMBL505769
10.15	IC50	0.07	nM	CHEMBL309823
10.15	IC50	0.07	nM	CHEMBL4798264
10.15	IC50	0.07	nM	CHEMBL296804
10.15	IC50	0.07	nM	CHEMBL566154
10.15	IC50	0.07	nM	CHEMBL1829034
10.15	IC50	0.07	nM	CHEMBL355240
10.10	IC50	0.08	nM	CHEMBL76119
10.10	IC50	0.08	nM	CHEMBL56511
10.10	IC50	0.08	nM	CHEMBL502641
10.10	IC50	0.08	nM	CHEMBL601470
10.10	IC50	0.08	nM	CHEMBL601683
10.10	IC50	0.08	nM	CHEMBL293807
10.10	IC50	0.08	nM	CHEMBL56822
10.05	IC50	0.09	nM	CHEMBL91402
10.05	IC50	0.09	nM	CHEMBL91737
10.05	IC50	0.09	nM	CHEMBL448863
10.05	IC50	0.09	nM	CHEMBL507665
10.05	IC50	0.09	nM	CHEMBL298835
10.05	IC50	0.09	nM	CHEMBL56511
10.05	IC50	0.09	nM	CHEMBL292619
10.05	IC50	0.09	nM	CHEMBL171389
10.00	IC50	0.1	nM	CHEMBL430931
10.00	IC50	0.1	nM	CHEMBL330687
10.00	IC50	0.1	nM	CHEMBL423683
10.00	IC50	0.1	nM	CHEMBL183768
10.00	IC50	0.1	nM	CHEMBL182181
10.00	IC50	0.1	nM	CHEMBL338417
10.00	IC50	0.1	nM	CHEMBL420936
10.00	IC50	0.1	nM	CHEMBL445303
10.00	IC50	0.1	nM	CHEMBL505992
10.00	IC50	0.1	nM	CHEMBL569443
10.00	IC50	0.1	nM	CHEMBL275603
10.00	IC50	0.1	nM	CHEMBL79984
10.00	IC50	0.1	nM	CHEMBL82938
10.00	IC50	0.1	nM	CHEMBL298835
10.00	IC50	0.1	nM	CHEMBL56822
10.00	IC50	0.1	nM	CHEMBL292619
10.00	IC50	0.1	nM	CHEMBL296804
10.00	IC50	0.1	nM	CHEMBL56520
10.00	IC50	0.1	nM	CHEMBL352778
10.00	IC50	0.1	nM	CHEMBL29018

PubChem BioAssay actives

2780 with measured affinity, of 3489 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
(2S)-2-[[(2S)-1-(3,5-dichlorophenyl)sulfonylpyrrolidine-2-carbonyl]amino]-3-[4-[(3,5-dichloropyridine-4-carbonyl)amino]phenyl]propanoic acid	241468: Inhibition of VLA-4 receptor of Jurkat cells in BURJ assay	ic50	<0.0001	uM
(2S)-2-[[(2S,4R)-1-(3-cyanophenyl)sulfonyl-4-(3,3-difluoropiperidin-1-yl)pyrrolidine-2-carbonyl]amino]-3-[4-[(3,5-dichloropyridine-4-carbonyl)amino]phenyl]propanoic acid	448164: Displacement of [35S]-labeled ligand from VLA4 in human Jurkat cells washed with buffer containing activating Mn2+ by competitive binding assay	ic50	<0.0001	uM
(5R)-6-[(1-carbamoylcyclohexyl)amino]-5-[[(2R)-2-[[4-[(2-methylphenyl)carbamoylamino]benzoyl]amino]-6-[[(E)-3-pyridin-3-ylprop-2-enoyl]amino]hexanoyl]amino]-6-oxohexanoic acid	303242: Inhibition of integrin alpha4beta1 receptor-mediated human Molt-4 cell adhesion to CS1 peptide	ic50	<0.0001	uM
(2S)-2-[[(2S,4R)-1-(3-cyanophenyl)sulfonyl-4-[cyclobutyl(2,2,2-trifluoroethyl)amino]pyrrolidine-2-carbonyl]amino]-3-[4-[(3,5-dichloropyridine-4-carbonyl)amino]phenyl]propanoic acid	448685: Displacement of [35S]-labeled ligand from VLA4 in human Jurkat cells washed with buffer containing non activating Ca2+ and Mg2+ by competitive binding assay	ic50	<0.0001	uM
(5S)-6-[[(2R)-1-amino-1-oxo-3-phenylpropan-2-yl]amino]-5-[[(2S)-2-[[2-[4-[(2-methylphenyl)carbamoylamino]phenyl]acetyl]amino]-6-[[(E)-3-pyridin-3-ylprop-2-enoyl]amino]hexanoyl]amino]-6-oxohexanoic acid	513088: Inhibition of Integrin alpha-4-beta-1-mediated adhesion in human jurkat cells	ic50	<0.0001	uM
(5S)-6-[(1-carbamoylcyclohexyl)amino]-5-[[(2S)-2-[[2-[4-[(2-methylphenyl)carbamoylamino]phenyl]acetyl]amino]-6-[[(E)-3-pyridin-3-ylprop-2-enoyl]amino]hexanoyl]amino]-6-oxohexanoic acid	1797818: Competitive Cell Adhesion Assay from Article 10.1021/jm070790o: “Highly Potent, Water Soluble Benzimidazole Antagonist for Activated alpha(4)beta(1) Integrin.”	ic50	<0.0001	uM
(2S)-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]-2-[[1-[2-(methylcarbamoylamino)ethyl]cyclopentanecarbonyl]amino]propanoic acid	217051: Inhibitory binding concentration determined against VCAM/VLA-4 in ELISA	ic50	0.0001	uM
(2S)-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]-2-[[1-(4-methylsulfonylbutyl)cyclobutanecarbonyl]amino]propanoic acid	216088: Inhibition of Very late antigen 4/vascular cell adhesion molecule 1 interaction in ELISA	ic50	0.0001	uM
(2S)-2-[[(2S)-1-(3,5-dichlorophenyl)sulfonylpyrrolidine-2-carbonyl]amino]-3-[4-(pyrrolidine-1-carbonyloxy)phenyl]propanoic acid	219967: Alpha4-beta1 integrin binding affinity was assessed by measuring the reduction in binding of [125I]VCAM-Ig to a suspension of Jurkat cells (a human T cell line alpha-4-beta-1-beta-7)	ic50	0.0001	uM
(2S)-2-[[C-[(2S)-1-(benzenesulfonyl)azetidin-2-yl]-N-(2,2,2-trifluoroethyl)carbonimidoyl]amino]-3-[4-(2,6-dimethoxyphenyl)phenyl]propanoic acid	1727046: Displacement of 125I-VCAM-Ig from VLA4 in human Jurkat cells incubated for 30 mins by scintillation counting method	ic50	0.0001	uM
(2S)-2-[[3-(benzenesulfonyl)piperidine-3-carbonyl]amino]-3-[4-(2,6-dimethoxyphenyl)phenyl]propanoic acid	216052: Binding affinity towards VLA-4 (alpha4 beta-1) receptor in human Jurkat cells using [125I]VCAM-Ig as radioligand	ic50	0.0001	uM
(2S)-2-[[3-(2-bromophenyl)sulfonylpiperidine-3-carbonyl]amino]-3-[4-(2,6-dimethoxyphenyl)phenyl]propanoic acid	216052: Binding affinity towards VLA-4 (alpha4 beta-1) receptor in human Jurkat cells using [125I]VCAM-Ig as radioligand	ic50	0.0001	uM
(2S)-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]-2-[[1-[2-(methylcarbamothioylamino)ethyl]cyclopentanecarbonyl]amino]propanoic acid	217051: Inhibitory binding concentration determined against VCAM/VLA-4 in ELISA	ic50	0.0001	uM
(2S)-3-[4-(2,6-dimethoxyphenyl)phenyl]-2-[[3-(3-methylimidazol-4-yl)sulfonylpiperidine-3-carbonyl]amino]propanoic acid	216052: Binding affinity towards VLA-4 (alpha4 beta-1) receptor in human Jurkat cells using [125I]VCAM-Ig as radioligand	ic50	0.0001	uM
3-[4-[(3,5-dichloropyridine-4-carbonyl)amino]phenyl]-2-[3-[2,2-dimethylpropanoyl(2-methylpropyl)amino]-4-ethylphenyl]propanoic acid	242815: Inhibition of Very late antigen-4 (VLA-4) expressing human leukemia cells (HL-60) aggregation with human Vascular cell adhesion molecule-1 (VCAM-1) expressing chinese hamster ovary (CHO) cells	ic50	0.0001	uM
(2S)-2-[[(2S)-1-(benzenesulfonyl)pyrrolidine-2-carbonyl]amino]-3-[4-(pyrrolidine-1-carbonyloxy)phenyl]propanoic acid	219967: Alpha4-beta1 integrin binding affinity was assessed by measuring the reduction in binding of [125I]VCAM-Ig to a suspension of Jurkat cells (a human T cell line alpha-4-beta-1-beta-7)	ic50	0.0001	uM
(2S)-2-[[3-(3-bromophenyl)sulfonylpiperidine-3-carbonyl]amino]-3-[4-(2,6-dimethoxyphenyl)phenyl]propanoic acid	216052: Binding affinity towards VLA-4 (alpha4 beta-1) receptor in human Jurkat cells using [125I]VCAM-Ig as radioligand	ic50	0.0001	uM
(2S)-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]-2-[[1-(4-methylsulfonylbutyl)cyclopentanecarbonyl]amino]propanoic acid	216088: Inhibition of Very late antigen 4/vascular cell adhesion molecule 1 interaction in ELISA	ic50	0.0001	uM
(2S)-2-[[(2S)-1-(3,5-dichlorophenyl)sulfonyl-2-methylazetidine-2-carbonyl]amino]-3-[4-(2,6-dimethoxyphenyl)phenyl]propanoic acid	216083: Inhibition of Mn2+ activated state of very late antigen 4 (VLA-4)	ic50	0.0001	uM
(2S)-2-[[(2S)-1-(3,5-dichlorophenyl)sulfonyl-2-methylpyrrolidine-2-carbonyl]amino]-3-[4-(2,6-dimethoxyphenyl)phenyl]propanoic acid	216069: Inhibition of [125I]VCAM-Ig binding to VLA-4 of Jurkat cells in the presence of [Ca2+]	ic50	0.0001	uM
3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]-2-[3-[2,2-dimethylpropanoyl(2-methylpropyl)amino]-4-propoxyphenyl]propanoic acid	242815: Inhibition of Very late antigen-4 (VLA-4) expressing human leukemia cells (HL-60) aggregation with human Vascular cell adhesion molecule-1 (VCAM-1) expressing chinese hamster ovary (CHO) cells	ic50	0.0001	uM
(2S)-2-[[amino-[(2S)-1-(benzenesulfonyl)azetidin-2-yl]methylidene]amino]-3-[4-(2,6-dimethoxyphenyl)phenyl]propanoic acid	1727046: Displacement of 125I-VCAM-Ig from VLA4 in human Jurkat cells incubated for 30 mins by scintillation counting method	ic50	0.0001	uM
(2S)-2-[[(2S,4R)-1-(3-cyanophenyl)sulfonyl-4-(cyclobutylamino)pyrrolidine-2-carbonyl]amino]-3-[4-[(3,5-dichloropyridine-4-carbonyl)amino]phenyl]propanoic acid	448685: Displacement of [35S]-labeled ligand from VLA4 in human Jurkat cells washed with buffer containing non activating Ca2+ and Mg2+ by competitive binding assay	ic50	0.0001	uM
(2S)-2-[[(2S)-1-(benzenesulfonyl)-2-ethylazetidine-2-carbonyl]amino]-3-[4-(2,6-dimethoxyphenyl)phenyl]propanoic acid	1727046: Displacement of 125I-VCAM-Ig from VLA4 in human Jurkat cells incubated for 30 mins by scintillation counting method	ic50	0.0001	uM
(2S)-2-[[(2S)-1-(3,5-dichlorophenyl)sulfonylpyrrolidine-2-carbonyl]amino]-3-[4-[2-(dimethylcarbamoyl)phenyl]phenyl]propanoic acid	217347: Antagonistic activity against VLA-4 integrin of human jurkat cells using [125I]VCAM-Ig as radioligand	ic50	0.0001	uM
(2S)-2-[[(2S)-1-(3,5-dichlorophenyl)sulfonylpyrrolidine-2-carbonyl]amino]-3-[4-[2-(methylcarbamoyl)phenyl]phenyl]propanoic acid	217347: Antagonistic activity against VLA-4 integrin of human jurkat cells using [125I]VCAM-Ig as radioligand	ic50	0.0001	uM
(2S)-2-[[(2S)-1-(3,5-dichlorophenyl)sulfonylpyrrolidine-2-carbonyl]amino]-3-[4-(2-methylsulfonylphenyl)phenyl]propanoic acid	217347: Antagonistic activity against VLA-4 integrin of human jurkat cells using [125I]VCAM-Ig as radioligand	ic50	0.0001	uM
(2S)-3-[4-(2-carbamoylphenyl)phenyl]-2-[[(2S)-1-(3,5-dichlorophenyl)sulfonylpyrrolidine-2-carbonyl]amino]propanoic acid	217347: Antagonistic activity against VLA-4 integrin of human jurkat cells using [125I]VCAM-Ig as radioligand	ic50	0.0001	uM
(5R)-5-[[(2R)-2-[[2-[4-(1,3-benzothiazol-2-ylamino)phenyl]acetyl]amino]-6-[[(E)-3-pyridin-3-ylprop-2-enoyl]amino]hexanoyl]amino]-6-[(1-carbamoylcyclohexyl)amino]-6-oxohexanoic acid	410577: Inhibition of human integrin alpha-4-beta-1-mediated MOLT4 cell adhesion to biotin-conjugated CS-1 peptide	ic50	0.0001	uM
(2S)-2-[[(2S,4R)-4-amino-1-(3,5-dichlorophenyl)sulfonylpyrrolidine-2-carbonyl]amino]-3-[4-[(3,5-dichloropyridine-4-carbonyl)amino]phenyl]propanoic acid	374772: Displacement of [125I]-(S)-2-((2S,4R)-4-(azetidin-1-yl)-1-(3-iodophenylsulfonyl)pyrrolidine-2-carboxamido)-3-(4-(3,5-dichloroisonicotinamido)phenyl)propanoic acid from VLA4 in human Jurkat cells washed with Hepes buffer by competitive binding assay	ic50	0.0001	uM
(2S)-2-[[(2S,4R)-1-(3,5-dichlorophenyl)sulfonyl-4-pyrrolidin-1-ylpyrrolidine-2-carbonyl]amino]-3-[4-[(3,5-dichloropyridine-4-carbonyl)amino]phenyl]propanoic acid	374772: Displacement of [125I]-(S)-2-((2S,4R)-4-(azetidin-1-yl)-1-(3-iodophenylsulfonyl)pyrrolidine-2-carboxamido)-3-(4-(3,5-dichloroisonicotinamido)phenyl)propanoic acid from VLA4 in human Jurkat cells washed with Hepes buffer by competitive binding assay	ic50	0.0001	uM
(2S)-2-[[(2S,4R)-4-(cyclobutylamino)-1-(3,5-dichlorophenyl)sulfonylpyrrolidine-2-carbonyl]amino]-3-[4-[(3,5-dichloropyridine-4-carbonyl)amino]phenyl]propanoic acid	374772: Displacement of [125I]-(S)-2-((2S,4R)-4-(azetidin-1-yl)-1-(3-iodophenylsulfonyl)pyrrolidine-2-carboxamido)-3-(4-(3,5-dichloroisonicotinamido)phenyl)propanoic acid from VLA4 in human Jurkat cells washed with Hepes buffer by competitive binding assay	ic50	0.0001	uM
(2S)-2-[[(2S,4R)-1-(3,5-dichlorophenyl)sulfonyl-4-piperidin-1-ylpyrrolidine-2-carbonyl]amino]-3-[4-[(3,5-dichloropyridine-4-carbonyl)amino]phenyl]propanoic acid	374772: Displacement of [125I]-(S)-2-((2S,4R)-4-(azetidin-1-yl)-1-(3-iodophenylsulfonyl)pyrrolidine-2-carboxamido)-3-(4-(3,5-dichloroisonicotinamido)phenyl)propanoic acid from VLA4 in human Jurkat cells washed with Hepes buffer by competitive binding assay	ic50	0.0001	uM
(8R,13R)-13-[[1-acetyl-3-(4-hydroxyphenyl)pyrrolidine-2-carbonyl]amino]-6,14-dioxo-10,11-dithia-7,15-diazaspiro[4.12]heptadecane-8-carboxylic acid	217340: Compound was evaluated for VCAM-VLA-4 antagonistic activity using solid phase assay	ic50	0.0001	uM
(2S)-3-[4-(2-cyanophenyl)phenyl]-2-[[(2S,3S)-1-(3,5-dichlorophenyl)sulfonyl-3-hydroxypyrrolidine-2-carbonyl]amino]propanoic acid	219966: Inhibition of integrin alpha4-beta1 of human Jurkat cells	ic50	0.0001	uM
(2S)-2-[[(2S,3S)-1-(3,5-dichlorophenyl)sulfonyl-3-hydroxypyrrolidine-2-carbonyl]amino]-3-[4-(2-methoxyphenyl)phenyl]propanoic acid	219966: Inhibition of integrin alpha4-beta1 of human Jurkat cells	ic50	0.0001	uM
(2S)-2-[[(2S)-1-(3,5-dichlorophenyl)sulfonyl-2-methylpyrrolidine-2-carbonyl]amino]-3-[4-(morpholine-4-carbonyloxy)phenyl]propanoic acid	219967: Alpha4-beta1 integrin binding affinity was assessed by measuring the reduction in binding of [125I]VCAM-Ig to a suspension of Jurkat cells (a human T cell line alpha-4-beta-1-beta-7)	ic50	0.0001	uM
(2S)-2-[[(2S)-1-(3,5-dichlorophenyl)sulfonylpyrrolidine-2-carbonyl]amino]-3-[4-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]phenyl]propanoic acid	219967: Alpha4-beta1 integrin binding affinity was assessed by measuring the reduction in binding of [125I]VCAM-Ig to a suspension of Jurkat cells (a human T cell line alpha-4-beta-1-beta-7)	ic50	0.0001	uM
(2S)-3-[4-[(2,6-dichlorobenzoyl)amino]phenyl]-2-[[(2S)-1-(3,5-dichlorophenyl)sulfonyl-2-methylpyrrolidine-2-carbonyl]amino]propanoic acid	216069: Inhibition of [125I]VCAM-Ig binding to VLA-4 of Jurkat cells in the presence of [Ca2+]	ic50	0.0001	uM
(2S)-2-[[(2S)-1-(3-chlorophenyl)sulfonylpyrrolidine-2-carbonyl]amino]-3-[4-[(3,5-dichloropyridine-4-carbonyl)amino]phenyl]propanoic acid	216069: Inhibition of [125I]VCAM-Ig binding to VLA-4 of Jurkat cells in the presence of [Ca2+]	ic50	0.0001	uM
(2S)-3-[4-[(3,5-dichloro-1-methylpyridin-1-ium-4-carbonyl)amino]phenyl]-2-[[(2S)-1-(3,5-dichlorophenyl)sulfonyl-2-methylpyrrolidine-2-carbonyl]amino]propanoic acid	216069: Inhibition of [125I]VCAM-Ig binding to VLA-4 of Jurkat cells in the presence of [Ca2+]	ic50	0.0001	uM
(2S)-2-[[(2S)-1-(3,5-dichlorophenyl)sulfonyl-2-methylpyrrolidine-2-carbonyl]amino]-3-[4-[(2,4-dichloropyridine-3-carbonyl)amino]phenyl]propanoic acid	216069: Inhibition of [125I]VCAM-Ig binding to VLA-4 of Jurkat cells in the presence of [Ca2+]	ic50	0.0001	uM
(2S)-3-[4-[(4-chloropyridine-3-carbonyl)amino]phenyl]-2-[[(2S)-1-(3,5-dichlorophenyl)sulfonyl-2-methylpyrrolidine-2-carbonyl]amino]propanoic acid	216070: Inhibition of [125I]VCAM-Ig binding to VLA-4 of Jurkat cells in the presence of Mn2+	ic50	0.0001	uM
(2S)-3-[4-[(2-chloro-4-methoxypyridine-3-carbonyl)amino]phenyl]-2-[[(2S)-1-(3,5-dichlorophenyl)sulfonyl-2-methylpyrrolidine-2-carbonyl]amino]propanoic acid	216069: Inhibition of [125I]VCAM-Ig binding to VLA-4 of Jurkat cells in the presence of [Ca2+]	ic50	0.0001	uM
(2S)-2-[[(2S)-1-(3,5-dichlorophenyl)sulfonyl-2-methylpyrrolidine-2-carbonyl]amino]-3-[4-[2,6-dimethoxy-4-(pyrrolidin-1-ylmethyl)phenyl]phenyl]propanoic acid	216069: Inhibition of [125I]VCAM-Ig binding to VLA-4 of Jurkat cells in the presence of [Ca2+]	ic50	0.0001	uM
(2S)-3-[4-[(4,6-dichloro-2-oxo-3H-pyridine-5-carbonyl)amino]phenyl]-2-[[(2S)-1-(3,5-dichlorophenyl)sulfonyl-2-methylpyrrolidine-2-carbonyl]amino]propanoic acid	216069: Inhibition of [125I]VCAM-Ig binding to VLA-4 of Jurkat cells in the presence of [Ca2+]	ic50	0.0001	uM
(2S)-2-[[(2S)-1-(benzenesulfonyl)pyrrolidine-2-carbonyl]amino]-3-[4-[(3,5-dichloropyridine-4-carbonyl)amino]phenyl]propanoic acid	216069: Inhibition of [125I]VCAM-Ig binding to VLA-4 of Jurkat cells in the presence of [Ca2+]	ic50	0.0001	uM
2-[[1-(benzenesulfonyl)pyrrolidine-2-carbonyl]amino]-3-[4-(2,6-dimethoxyphenyl)phenyl]propanoic acid	218412: Inhibition of [125I]VCAM-Ig binding to human integrin alpha4-beta1 (VLA-4) of Jurkat cells	ic50	0.0001	uM
2-[[1-(benzenesulfonyl)cyclopentanecarbonyl]amino]-3-[4-(2,6-dimethoxyphenyl)phenyl]propanoic acid	218412: Inhibition of [125I]VCAM-Ig binding to human integrin alpha4-beta1 (VLA-4) of Jurkat cells	ic50	0.0001	uM
(2S)-2-[[(2S)-1-(3,5-dichlorophenyl)sulfonyl-2-methylpyrrolidine-2-carbonyl]amino]-3-(4-pyridin-2-ylphenyl)propanoic acid	217347: Antagonistic activity against VLA-4 integrin of human jurkat cells using [125I]VCAM-Ig as radioligand	ic50	0.0001	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression, increases abundance	5
(+)-JQ1 compound	decreases expression, decreases reaction, increases expression	4
trichostatin A	affects cotreatment, increases expression	3
Tretinoin	increases expression, decreases expression	3
Valproic Acid	affects cotreatment, increases expression	3
bisphenol A	affects cotreatment, increases methylation, decreases expression, decreases methylation	2
potassium chromate(VI)	affects cotreatment, decreases expression, increases expression	2
mercuric bromide	decreases expression, affects cotreatment	2
Benzo(a)pyrene	increases expression, increases methylation	2
Doxorubicin	decreases expression, increases expression	2
Lipopolysaccharides	decreases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Plant Extracts	increases expression, decreases expression, decreases reaction, increases abundance, affects cotreatment	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
p-Chloromercuribenzoic Acid	decreases expression, affects cotreatment	2
aristolochic acid I	decreases expression	1
napabucasin	decreases expression	1
4-oxoretinoic acid	increases expression	1
methylmercuric chloride	decreases expression	1
oxybenzone	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
bis(tri-n-butyltin)oxide	increases expression	1
tributyltin	increases expression	1
arsenite	increases methylation	1
methylparaben	decreases expression	1
cobaltous chloride	increases expression	1
butyraldehyde	increases expression	1
ochratoxin A	increases expression	1
methylmercury II	increases expression	1

ChEMBL screening assays

299 unique, capped per target: 282 binding, 17 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1030320	Binding	Inhibition of integrin alpha-4-beta-1-mediated U937 and Jurkat cell adhesion to VCAM-1 coated surface up to 100 uM by BCECF fluorescence measurement	Cyclic glycopeptidomimetics through a versatile sugar-based scaffold. — Bioorg Med Chem Lett
CHEMBL1833598	Functional	Antagonist activity at alpha4beta1 integrin	Modeling the molecular basis for α4β1 integrin antagonism. — Bioorg Med Chem

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1NI	Abcam K-562 ITGA4 KO	Cancer cell line	Female
CVCL_D2K3	Abcam Raji ITGA4 KO	Cancer cell line	Male
CVCL_D9HF	Ubigene HEK293 ITGA4 KO	Transformed cell line	Female
CVCL_ST27	HAP1 ITGA4 (-) 1	Cancer cell line	Male
CVCL_ST28	HAP1 ITGA4 (-) 2	Cancer cell line	Male
CVCL_UQ84	Abcam Jurkat ITGA4 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT00000114	PHASE3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	PHASE3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	PHASE3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	PHASE3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT04636853	PHASE3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	PHASE3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	PHASE3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	PHASE3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT00100230	PHASE2	COMPLETED	DHA and X-Linked Retinitis Pigmentosa
NCT00447980	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Participants With Early Stage Retinitis Pigmentosa
NCT00447993	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
NCT01233609	PHASE2	COMPLETED	Trial of Oral Valproic Acid for Retinitis Pigmentosa
NCT01399515	PHASE2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01530659	PHASE2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT01560715	PHASE2	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT02609165	PHASE2	COMPLETED	Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema
NCT02661711	PHASE2	COMPLETED	Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
NCT02804360	PHASE2	UNKNOWN	Intravitreal Dexamethasone Implant in Retinitis Pigmentosa-related Macular Edema- a Retrospective Study
NCT02837640	PHASE2	UNKNOWN	Studying a Potential Protective Effect of L-Dopa on Retinitis Pigmentosa
NCT03073733	PHASE2	COMPLETED	Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04356716	PHASE2	COMPLETED	Sildenafil for Treatment of Choroidal Ischemia
NCT04604899	PHASE2	COMPLETED	Safety of Repeat Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa
NCT04763369	PHASE2	UNKNOWN	Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)
NCT04864496	PHASE2	UNKNOWN	Effects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05085964	PHASE2	TERMINATED	An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa
NCT05392179	PHASE2	COMPLETED	A Study in Subjects With Retinitis Pigmentosa
NCT06627179	PHASE2	RECRUITING	Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT06628947	PHASE2	RECRUITING	A Phase II Study of Intravitreal KIO-301 in Patients With Late-stage Retinitis Pigmentosa
NCT06912633	PHASE2	RECRUITING	Safety of a Single, Intravitreal Injection of 6.0M jCell (Famzeretcel) in Retinitis Pigmentosa (RP)
NCT00063765	PHASE1	COMPLETED	Evaluation of Safety of Ciliary Neurotrophic Factor Implants in the Eye
NCT00065455	PHASE1	COMPLETED	Investigating the Effect of Vitamin A Supplementation on Retinitis Pigmentosa
NCT00458575	PHASE1	TERMINATED	A Study to Evaluate the Safety of CNTO 2476 in Patients With Advanced Retinitis Pigmentosa
NCT01068561	PHASE1	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa