VCAM1

Summary

VCAM1 (vascular cell adhesion molecule 1, HGNC:12663) is a protein-coding gene on chromosome 1p21.2, encoding Vascular cell adhesion protein 1 (P19320). Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation.

This gene is a member of the Ig superfamily and encodes a cell surface sialoglycoprotein expressed by cytokine-activated endothelium. This type I membrane protein mediates leukocyte-endothelial cell adhesion and signal transduction, and may play a role in the development of artherosclerosis and rheumatoid arthritis. Three alternatively spliced transcripts encoding different isoforms have been described for this gene.

Source: NCBI Gene 7412 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 101 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001078

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12663
Approved symbol	VCAM1
Name	vascular cell adhesion molecule 1
Location	1p21.2
Locus type	gene with protein product
Status	Approved
Aliases	CD106
Ensembl gene	ENSG00000162692
Ensembl biotype	protein_coding
OMIM	192225
Entrez	7412

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000294728, ENST00000347652, ENST00000370115, ENST00000370119, ENST00000603679, ENST00000650339, ENST00000855907, ENST00000949395, ENST00000949396

RefSeq mRNA: 3 — MANE Select: NM_001078 NM_001078, NM_001199834, NM_080682

CCDS: CCDS55617, CCDS773, CCDS774

Canonical transcript exons

ENST00000294728 — 9 exons

Exon	Start	End
ENSE00001067751	100734502	100734768
ENSE00001067753	100731198	100731518
ENSE00001067755	100723020	100723340
ENSE00001067756	100729107	100729382
ENSE00001067757	100720476	100720751
ENSE00001067758	100724624	100724890
ENSE00001067759	100732418	100732684
ENSE00001167778	100738123	100739045
ENSE00001167786	100719742	100719924

Expression profiles

Bgee: expression breadth ubiquitous, 257 present calls, max score 99.13.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.7029 / max 910.3466, expressed in 928 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
4248	14.7029	928

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cartilage tissue	UBERON:0002418	99.13	gold quality
trabecular bone tissue	UBERON:0002483	98.99	gold quality
parietal pleura	UBERON:0002400	98.23	gold quality
vena cava	UBERON:0004087	98.08	gold quality
tendon of biceps brachii	UBERON:0008188	98.08	gold quality
spleen	UBERON:0002106	97.98	gold quality
adrenal tissue	UBERON:0018303	97.94	gold quality
renal glomerulus	UBERON:0000074	97.91	gold quality
metanephric glomerulus	UBERON:0004736	97.80	gold quality
synovial joint	UBERON:0002217	97.38	gold quality
nephron tubule	UBERON:0001231	97.34	gold quality
pleura	UBERON:0000977	97.21	gold quality
kidney epithelium	UBERON:0004819	97.14	gold quality
lymph node	UBERON:0000029	96.63	gold quality
decidua	UBERON:0002450	96.19	gold quality
layer of synovial tissue	UBERON:0007616	95.41	gold quality
visceral pleura	UBERON:0002401	95.40	gold quality
epithelium of nasopharynx	UBERON:0001951	95.16	gold quality
nasopharynx	UBERON:0001728	95.15	gold quality
germinal epithelium of ovary	UBERON:0001304	95.05	gold quality
choroid plexus epithelium	UBERON:0003911	94.62	gold quality
kidney	UBERON:0002113	93.36	gold quality
metanephros	UBERON:0000081	93.25	gold quality
adult mammalian kidney	UBERON:0000082	93.20	gold quality
vermiform appendix	UBERON:0001154	93.11	gold quality
adrenal gland	UBERON:0002369	92.76	gold quality
mucosa of urinary bladder	UBERON:0001259	92.64	gold quality
cortex of kidney	UBERON:0001225	92.43	gold quality
colonic epithelium	UBERON:0000397	92.33	gold quality
ventricular zone	UBERON:0003053	92.26	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-MTAB-8322	yes	1536.75
E-MTAB-7407	yes	597.59
E-ANND-5	yes	582.58
E-GEOD-135922	yes	33.99
E-HCAD-4	yes	24.46
E-MTAB-10553	yes	23.55
E-ANND-3	yes	23.25
E-HCAD-9	yes	19.88
E-GEOD-93593	yes	14.84
E-GEOD-83139	yes	13.16
E-CURD-112	yes	11.19
E-GEOD-124858	no	807.76

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, APLNR, AR, CLOCK, CREB1, EP300, EPAS1, FLCN, FOS, FOXC1, FOXO1, GATA2, GATA3, GATA4, GATA6, HDAC4, HOXA9, ID3, IKBKB, IL1B, IRF1, IRF2, IRF6, JUN, KLF4, MYC, NFATC1, NFE2L2, NFKB1, NFKB2, NFKB, NFKBIA, NFKBID, NR4A3, PARP1, PGR, POU2F1, PPARA, PPARD, PPARG

miRNA regulators (miRDB)

49 targeting VCAM1, 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-4692	100.00	67.32	2066
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-507	99.97	70.11	1915
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-557	99.96	70.01	1640
HSA-MIR-545-3P	99.95	70.74	2783
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-7845-5P	99.88	64.88	771
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-202-3P	99.84	71.41	1290
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-4766-5P	99.75	69.23	2662
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-1284	99.67	73.56	1353

Literature-anchored findings (GeneRIF, showing 40)

• Premature labor is associated with up-regulation of adhesion molecules in the lower uterine segment (PMID:11776680)
• Soluble VCAM-1 is a very early marker of endothelial cell activation in cardiopulmonary bypass. (PMID:11817523)
• significant increase in plasma levels between day 1 and day 5 of G-CSF-induced stem cell mobilization; possible effect on leukocyte-endothelial cell interactions (PMID:11847011)
• Testosterone attenuates expression of vascular cell adhesion molecule-1 by conversion to estradiol by aromatase in endothelial cells: implications in atherosclerosis (PMID:11904449)
• Elevated soluble CD40 ligand is related to the endothelial adhesion molecules in patients with acute coronary syndrome. (PMID:11922919)
• 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)
• relation between glycemic control, hyperinsulinism and plasma concentration in patients with glucosse intolerance or NIDDM (PMID:11935152)
• Results suggest that exogenous NO inhibits VCAM-1 expression via suppression of NF-kappaB through a cGMP-independent pathway. (PMID:11961404)
• women with stage III and IV endometriosis had higher serum concentrations of soluble VCAM-1, lower serum concentration of soluble ICAM-1 (PMID:11963839)
• The tumor necrosis factor-alpha-stimulated redox-sensitive vascular cell adhesion molecule-1 selective signaling pathway in endothelial cells depends upon isoprenylcysteine carboxyl methyltransferase as a critical component. (PMID:12006387)
• During leukocyte adhesion VCAM-1, ICAM-1, and activated moesin and ezrin clustered in an endothelial actin-rich docking structure that anchored and partially embraced the leukocyte containing other cytoskeletal components (PMID:12082081)
• the preferential expression of VCAM-1 on the endothelium of femoral and iliac arteries in thromboangiitis obliterans (PMID:12086338)
• VCAM-1/alpha4 integrin interactions mediate monocyte adhesion to human saphenous vein (PMID:12097820)
• signal transduction pathways involved in rheumatoid arthritis synovial fibroblast interleukin-18-induced vascular cell adhesion molecule-1 expression (PMID:12105209)
• VCAM-1 expression via effects on interferon regulatory factor-1 expression and activity (PMID:12115600)
• E-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular adhesion molecule-1 (VCAM-1) were measured in serum from hypertensive patients with LV hypertrophy (PMID:12172318)
• Downregulation of vcam-1 is associated with nodal metastasis in breast cancer (PMID:12172576)
• Synchronized human hematopoietic progenitor cell adhesion fluctuates reversibly during cell cycle transit in ex vivo culture (PMID:12351381)
• induction by tumor necrosis factor alpha (PMID:12387879)
• Of the 10 candidate SNPs analyzed in this pilot study, the variant allele of the nonsynonymous SNP, VCAM1 G1238C, may be associated with protection from stroke. (PMID:12393616)
• Relationship between pathological changes and the expression of vascular cell adhesion molecule-1 in the placenta of patients with pregnancy-induced hypertension complicated by intrauterine growth retardation (PMID:12433638)
• VCAM1 stimulation by thrombin in endothelial cells is mediated by protein kinase C-delta-NF-kappa B and PKC-zeta-GATA signaling pathways (PMID:12493764)
• VCAM1 expression is induced by p38-mediated TNFalpha and suppressed by JNK in human cells (PMID:12587980)
• In adults with sickle cell disease, steady-state serum sVCAM-1 levels do not seem to reflect clinical disease severity, but may reflect bone marrow activity in SCD, underlying the pleiotropic nature of adhesion molecules in vivo. (PMID:12601490)
• Strongly expressed in histological type II of rheumatoid arthritis. (PMID:12643440)
• Crosslinking of CD44 on osteoblastic cells with specific antibodies augmented the expression of intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 (PMID:12650924)
• Endothelial cells have increased expression of VCAM-1, E-selectin, and ICAM-1 when exposed to sickle blood cells. (PMID:12673844)
• VCAM-1-induced, Rac-dependent signaling plays a key role in the modulation of vascular-endothelial cadherin-mediated endothelial cell-cell adhesion and leukocyte extravasation. (PMID:12700137)
• regulation of expression in osteoblasts by interleukin 13 (PMID:12704784)
• a novel role for the P2Y2 receptor in the p38- and Rho kinase-dependent expression of VCAM-1 that mediates the recruitment of monocytes by vascular endothelium associated with the development of atherosclerosis (PMID:12714597)
• Soluble VCAM-1 markedly enhances phosphorylation of both p38 and focal adhesion kinase, but not ERK1/2, in endothelial cells, endothelial cell migration activity in vitro, and neovascularization in Matrigel in vivo. (PMID:12759453)
• Extravasated and oxidized LDL in xanthoma adds to foam cell recruitment by activating tyrosine kinase and inducing adhesion of monocytes to dermal microvascular endothelial cells through VCAM-1 and E-selectin. (PMID:12788528)
• Blood levels do not differ in normal and coronary artery disease patients. (PMID:12940514)
• During infusion of triacylglycerol, PAI-1 increased to approximately 2.6 fold higher levels while tPA and adipsin were unaffected; changes in sVCAM-1 were significantly correlated with those seen for PAI-1. (PMID:12958610)
• presence of vascular cell adhesion molecule (VCAM-1) in placental villi is specific to developmental stage, and it is decreased in fetal growth restriction which could be attributed to the uteroplacental deficiency (PMID:12969778)
• Adrenomedullin and ACTH induce cell surface expression of adhesion molecules E-selectin, VCAM-1, and ICAM-1 on human umbilical vein endothelial cells. (PMID:14534081)
• 11,12-EET analogues were synthesized and compared using a human endothelial cell based TNF-alpha-induced VCAM-1 expression assay. (PMID:14592496)
• Novel androgen receptor/NF-kappaB mediated mechanism for VCAM-1 expression and monocyte adhesion operating in male endothelial cells that may represent an important unrecognized mechanism for the male predisposition to atherosclerosis. (PMID:14684616)
• study demonstrates that overexpression of RORalpha1 and RORalpha4 inhibits TNF-alpha induced expression of VCAM-1 and ICAM-1 in human umbilical vein endothelial cells by inhibiting the NF-B signaling pathway (PMID:14741380)
• sVCAM-1 was associated with dengue disease severity and the time post infection; a significant difference was found in the plasma levels of sVCAM-1 between dengue shock syndrome and dengue fever patients (PMID:14748068)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	vcam1b	ENSDARG00000062479
mus_musculus	Vcam1	ENSMUSG00000027962
rattus_norvegicus	Vcam1	ENSRNOG00000014333
caenorhabditis_elegans		WBGENE00007736
caenorhabditis_elegans		WBGENE00011418

Paralogs (36): CNTN1 (ENSG00000018236), CDON (ENSG00000064309), NEO1 (ENSG00000067141), SDK2 (ENSG00000069188), IGSF9B (ENSG00000080854), IGSF9 (ENSG00000085552), NRCAM (ENSG00000091129), MXRA5 (ENSG00000101825), IGDCC4 (ENSG00000103742), CNTN3 (ENSG00000113805), IGSF21 (ENSG00000117154), CNTN6 (ENSG00000134115), CHL1 (ENSG00000134121), PTPRQ (ENSG00000139304), CNTN4 (ENSG00000144619), BOC (ENSG00000144857), SDK1 (ENSG00000146555), HMCN2 (ENSG00000148357), NCAM1 (ENSG00000149294), CNTN5 (ENSG00000149972), IGSF10 (ENSG00000152580), ROBO4 (ENSG00000154133), ROBO3 (ENSG00000154134), NCAM2 (ENSG00000154654), NFASC (ENSG00000163531), PRTG (ENSG00000166450), ROBO1 (ENSG00000169855), DSCAM (ENSG00000171587), IGDCC3 (ENSG00000174498), VSIG10 (ENSG00000176834), DSCAML1 (ENSG00000177103), CNTN2 (ENSG00000184144), ROBO2 (ENSG00000185008), VSIG10L (ENSG00000186806), DCC (ENSG00000187323), L1CAM (ENSG00000198910)

Protein

Protein identifiers

Vascular cell adhesion protein 1 — P19320 (reviewed: P19320)

Alternative names: INCAM-100

All UniProt accessions (3): A0A3B3ISS8, E9PDD2, P19320

UniProt curated annotations — full annotation on UniProt →

Function. Cell adhesion glycoprotein predominantly expressed on the surface of endothelial cells that plays an important role in immune surveillance and inflammation. Acts as a major regulator of leukocyte adhesion to the endothelium through interaction with different types of integrins. During inflammatory responses, binds ligands on the surface of activated endothelial cells to initiate the activation of calcium channels and the plasma membrane-associated small GTPase RAC1 leading to leukocyte transendothelial migration. Also serves as a quality-control checkpoint for entry into bone marrow by providing a ‘don’t-eat-me’ stamping in the context of major histocompatibility complex (MHC) class-I presentation.

Subcellular location. Cell membrane Secreted.

Tissue specificity. Expressed on inflamed vascular endothelium, as well as on macrophage-like and dendritic cell types in both normal and inflamed tissue.

Post-translational modifications. Cleaved by the metalloproteinase ADAM17 to generate the soluble form. Sialoglycoprotein. Ubiquitinated by TRIM65 via ‘Lys-48’-linked ubiquitination; leading to proteasomal degradation.

Domain organisation. Either the first or the fourth Ig-like C2-type domain is required for VLA4-dependent cell adhesion.

Induction. By pro-inflammatory cytokines, including TNFalpha, and also by ROS, oxidized low density lipoprotein, high glucose concentration, toll-like receptor agonists, and shear stress.

Miscellaneous. Major isoform.

Isoforms (3)

UniProt ID	Names	Canonical?
P19320-1	1, Long, VCAM-7D	yes
P19320-2	2, Short, VCAM-6D
P19320-3	3

RefSeq proteins (3): NP_001069, NP_001186763, NP_542413 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR003987	ICAM_VCAM_N	Domain
IPR003989	VCAM-1	Family
IPR007110	Ig-like_dom	Domain
IPR008424	Ig_C2-set	Domain
IPR013098	Ig_I-set	Domain
IPR013106	Ig_V-set	Domain
IPR013151	Immunoglobulin_dom	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR047012	ICAM_VCAM	Family

Pfam: PF00047, PF05790, PF07679, PF13927

UniProt features (57 total): strand 15, domain 7, sequence variant 7, glycosylation site 6, disulfide bond 6, sequence conflict 3, helix 3, chain 2, splice variant 2, topological domain 2, mutagenesis site 2, signal peptide 1, transmembrane region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
1VCA	X-RAY DIFFRACTION	1.8
1VSC	X-RAY DIFFRACTION	1.9
1IJ9	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P19320-F1	84.24	0.50

Functional residue map

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

Disulfide bonds (6): 47–95, 52–99, 137–195, 246–291, 335–383, 534–579

Glycosylation sites (6): 273, 365, 417, 463, 531, 561

Mutagenesis-validated functional residues (2):

Position	Phenotype
730	loss of rac1 activation and subsequent leukocyte transmigration.
737	loss of rac1 activation and subsequent leukocyte transmigration.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-198933	Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
R-HSA-216083	Integrin cell surface interactions
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling
R-HSA-877300	Interferon gamma signaling

MSigDB gene sets: 416 (showing top): GSE45365_NK_CELL_VS_BCELL_UP, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_RESPONSE_TO_ETHANOL, BERENJENO_ROCK_SIGNALING_NOT_VIA_RHOA_DN, GOBP_RESPONSE_TO_IONIZING_RADIATION, GOBP_RESPONSE_TO_ZINC_ION, GOBP_HETEROPHILIC_CELL_CELL_ADHESION, MCLACHLAN_DENTAL_CARIES_UP, GOBP_CELL_CHEMOTAXIS, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE

GO Biological Process (27): response to hypoxia (GO:0001666), chronic inflammatory response (GO:0002544), inflammatory response (GO:0006954), cell adhesion (GO:0007155), heterophilic cell-cell adhesion (GO:0007157), leukocyte cell-cell adhesion (GO:0007159), cell-matrix adhesion (GO:0007160), response to nutrient (GO:0007584), amine metabolic process (GO:0009308), response to zinc ion (GO:0010043), response to ionizing radiation (GO:0010212), membrane to membrane docking (GO:0022614), B cell differentiation (GO:0030183), response to lipopolysaccharide (GO:0032496), cell-cell adhesion mediated by integrin (GO:0033631), heterotypic cell-cell adhesion (GO:0034113), response to nicotine (GO:0035094), cellular response to vascular endothelial growth factor stimulus (GO:0035924), positive regulation of T cell proliferation (GO:0042102), response to ethanol (GO:0045471), leukocyte tethering or rolling (GO:0050901), cell chemotaxis (GO:0060326), innervation (GO:0060384), cardiac neuron differentiation (GO:0060945), cellular response to tumor necrosis factor (GO:0071356), cellular response to amyloid-beta (GO:1904646), cell-cell adhesion (GO:0098609)

GO Molecular Function (4): integrin binding (GO:0005178), primary methylamine oxidase activity (GO:0008131), cell adhesion molecule binding (GO:0050839), cell adhesion mediator activity (GO:0098631)

GO Cellular Component (16): podosome (GO:0002102), obsolete extracellular space (GO:0005615), early endosome (GO:0005769), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794), plasma membrane (GO:0005886), microvillus (GO:0005902), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), filopodium (GO:0030175), sarcolemma (GO:0042383), apical part of cell (GO:0045177), extracellular exosome (GO:0070062), alpha9-beta1 integrin-vascular cell adhesion molecule-1 complex (GO:0071065), extracellular region (GO:0005576), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Adaptive Immune System	1
Extracellular matrix organization	1
Signaling by Interleukins	1
Interferon Signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell-cell adhesion	4
cellular anatomical structure	4
actin-based cell projection	3
response to chemical	2
cell adhesion molecule binding	2
cytoplasm	2
endomembrane system	2
intracellular membrane-bounded organelle	2
plasma membrane	2
response to stress	1
response to decreased oxygen levels	1
inflammatory response	1
defense response	1
cellular process	1
cell-substrate adhesion	1
response to nutrient levels	1
metabolic process	1
response to metal ion	1
response to radiation	1
membrane docking	1
lymphocyte differentiation	1
B cell activation	1
response to molecule of bacterial origin	1
response to lipid	1
response to oxygen-containing compound	1
cell adhesion mediated by integrin	1
cellular response to growth factor stimulus	1
T cell proliferation	1
regulation of T cell proliferation	1
positive regulation of lymphocyte proliferation	1
positive regulation of T cell activation	1
response to alcohol	1
signaling receptor binding	1
protein-containing complex binding	1
oxidoreductase activity, acting on the CH-NH2 group of donors, oxygen as acceptor	1
protein binding	1
cell adhesion	1
endosome	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

4532 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VCAM1	ICAM1	P05362	999
VCAM1	ITGB2	P05107	997
VCAM1	ITGA4	P13612	997
VCAM1	ITGB1	P05556	996
VCAM1	CD44	P16070	994
VCAM1	ITGAL	P20701	992
VCAM1	SELPLG	Q14242	990
VCAM1	ITGAM	P11215	986
VCAM1	FN1	P02751	982
VCAM1	SELE	P16111	976
VCAM1	CXCR4	P30991	976
VCAM1	SELL	P14151	969
VCAM1	SELP	P16109	963
VCAM1	ITGAD	Q13349	962
VCAM1	SPARC	P09486	961

IntAct

17 interactions, top by confidence:

A	B	Type	Score
VCAM1	ITGB1	psi-mi:“MI:0914”(association)	0.660
ITGB1	VCAM1	psi-mi:“MI:0915”(physical association)	0.660
VCAM1	PSMD11	psi-mi:“MI:0914”(association)	0.530
VCAM1	iglC2	psi-mi:“MI:0915”(physical association)	0.370
PB2	SEC15L3	psi-mi:“MI:0914”(association)	0.350
VCAM1	APOA1	psi-mi:“MI:0914”(association)	0.350
VCAM1	ATP2A1	psi-mi:“MI:0914”(association)	0.350
VCAM1	ATP1A3	psi-mi:“MI:0914”(association)	0.350
VCAM1		psi-mi:“MI:0914”(association)	0.350
BRCA1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (482): BAG6 (Affinity Capture-Western), VCP (Affinity Capture-Western), VCAM1 (Biochemical Activity), VCAM1 (Affinity Capture-Western), VCAM1 (Affinity Capture-Western), SEMA4D (Affinity Capture-MS), FANK1 (Affinity Capture-MS), BCS1L (Affinity Capture-MS), PODXL2 (Affinity Capture-MS), APOA1 (Affinity Capture-MS), INTS8 (Affinity Capture-MS), WDFY3 (Affinity Capture-MS), TUBA4A (Affinity Capture-MS), VCAM1 (Affinity Capture-Western), TRIM65 (Affinity Capture-Western)

ESM2 similar proteins: A0A8M2B818, B0CLX4, O35112, O46634, O46651, O70535, P01872, P14719, P16284, P19320, P23088, P27931, P29533, P29534, P42082, P42292, P42702, P42703, P43303, P51866, P97710, P97797, Q00609, Q01638, Q08481, Q13740, Q1WIM2, Q28260, Q3SWT0, Q501W4, Q5XNR9, Q61490, Q62611, Q6DJ83, Q6GMZ9, Q7TSP5, Q7Z7D3, Q8BLQ9, Q8N3J6, Q8R2Y2

Diamond homologs: A4FUY1, A6NDA9, D3ZB51, E9PZ19, G5EGI7, O02827, O95428, P0C192, P0C5H6, P0CC10, P14781, P16419, P19320, P21802, P21803, P29294, P35918, P35968, P56276, Q02173, Q05BQ1, Q149C3, Q14CZ8, Q15772, Q1ENI8, Q28824, Q5DTJ9, Q640R3, Q6GQU6, Q6UY18, Q6V4S5, Q8AXB3, Q8C031, Q8JG38, Q8N475, Q90773, Q91286, Q95YM9, Q967D7, Q96JA1

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
VCAM1	“up-regulates activity”	“A4/b1 integrin”	binding
“AD/b2 integrin”	“up-regulates activity”	VCAM1	binding
hsa-mir-126-5p	“down-regulates quantity by repression”	VCAM1	“post transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	81
Likely benign	13
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

1229 predictions. Top by Δscore:

Variant	Effect	Δscore
1:100719921:GCTT:G	donor_gain	1.0000
1:100719925:G:GG	donor_gain	1.0000
1:100723189:G:GT	donor_gain	1.0000
1:100723210:TTTGG:T	donor_gain	1.0000
1:100723214:G:GT	donor_gain	1.0000
1:100723307:G:GG	donor_gain	1.0000
1:100723341:G:GG	donor_gain	1.0000
1:100724622:A:AG	acceptor_gain	1.0000
1:100724623:G:GA	acceptor_gain	1.0000
1:100724623:GT:G	acceptor_gain	1.0000
1:100731196:A:AG	acceptor_gain	1.0000
1:100731197:G:GA	acceptor_gain	1.0000
1:100731197:GC:G	acceptor_gain	1.0000
1:100734500:A:AG	acceptor_gain	1.0000
1:100734501:G:GG	acceptor_gain	1.0000
1:100734501:GTT:G	acceptor_gain	1.0000
1:100734699:G:GT	donor_gain	1.0000
1:100734768:GGT:G	donor_loss	1.0000
1:100734769:G:C	donor_loss	1.0000
1:100734770:T:G	donor_loss	1.0000
1:100719920:AGCTT:A	donor_gain	0.9900
1:100719921:GCTTG:G	donor_gain	0.9900
1:100719922:CTT:C	donor_gain	0.9900
1:100720474:A:AG	acceptor_gain	0.9900
1:100720475:G:GG	acceptor_gain	0.9900
1:100720475:GCTC:G	acceptor_gain	0.9900
1:100720475:GCTCA:G	acceptor_gain	0.9900
1:100720562:GGCT:G	donor_gain	0.9900
1:100720563:GCTG:G	donor_gain	0.9900
1:100720752:G:GG	donor_gain	0.9900

AlphaMissense

4860 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:100720588:G:C	W59C	0.994
1:100720588:G:T	W59C	0.994
1:100720586:T:A	W59R	0.992
1:100720586:T:C	W59R	0.992
1:100720694:T:A	C95S	0.990
1:100720695:G:C	C95S	0.990
1:100729217:T:A	W347R	0.989
1:100729217:T:C	W347R	0.989
1:100729219:G:C	W347C	0.988
1:100729219:G:T	W347C	0.988
1:100723088:T:C	C137R	0.986
1:100720650:T:C	L80P	0.984
1:100732528:T:A	W546R	0.984
1:100732528:T:C	W546R	0.984
1:100720694:T:C	C95R	0.983
1:100724734:T:A	W258R	0.982
1:100724734:T:C	W258R	0.982
1:100734705:T:G	Y666D	0.982
1:100724833:T:C	C291R	0.981
1:100720550:T:C	C47R	0.979
1:100720696:C:G	C95W	0.979
1:100723262:T:C	C195R	0.979
1:100724698:T:C	C246R	0.979
1:100724736:G:C	W258C	0.979
1:100724736:G:T	W258C	0.979
1:100720550:T:A	C47S	0.978
1:100720551:G:C	C47S	0.978
1:100724833:T:A	C291S	0.977
1:100724834:G:C	C291S	0.977
1:100731440:T:C	C483R	0.977

dbSNP variants (sampled 300 via entrez): RS1000371179 (1:100724810 T>A,C,G), RS1000903747 (1:100730707 A>G), RS1001093955 (1:100739000 G>A), RS1001199909 (1:100730806 T>G), RS1001231059 (1:100736954 A>G), RS1001248516 (1:100722928 C>T), RS1001253475 (1:100738585 T>C,G), RS1001356388 (1:100731091 C>G,T), RS1001447037 (1:100723630 T>C,G), RS1001530754 (1:100734816 C>T), RS1001563482 (1:100735259 G>A), RS1001674937 (1:100728360 A>G), RS1001703437 (1:100737248 T>G), RS1001859840 (1:100736580 A>G), RS1002081032 (1:100729792 A>G)

Disease associations

OMIM: gene MIM:192225 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001198_33	Multiple sclerosis	3.000000e-10
GCST001198_77	Multiple sclerosis	4.000000e-08
GCST005531_101	Multiple sclerosis	2.000000e-16
GCST005532_3	Sjögren’s syndrome	4.000000e-06
GCST009597_20	Multiple sclerosis	1.000000e-22
GCST90002388_610	Lymphocyte count	3.000000e-13
GCST90002389_59	Lymphocyte percentage of white cells	1.000000e-09
GCST90002399_44	Neutrophil percentage of white cells	6.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004587	lymphocyte count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3735 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 244 (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
CHEMBL83626	SUCCINOBUCOL	3	244

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

Binding affinities (BindingDB)

36 measured of 39 human assays (40 total across all organisms); most potent 36 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(2S)-2-[[2,6-difluoro-4-[[5-(1,2,4-triazol-1-yl)-2-pyridinyl]sulfonylamino]benzoyl]amino]-3-[4-(1-methyl-2,4-dioxo-4aH-pyrido[3,4-d]pyrimidin-1-ium-3-yl)phenyl]propanoic acid	IC50	13 nM	US-9533985: Sulfonamide derivative and medicinal use thereof
(2S)-2-[[2,6-difluoro-4-[(5-pyrimidin-5-yl-2-pyridinyl)sulfonylamino]benzoyl]amino]-3-[4-(1-methyl-2,4-dioxo-4a,5,6,7,8,8a-hexahydropyrido[3,4-d]pyrimidin-3-yl)phenyl]propanoic acid	IC50	18 nM	US-9533985: Sulfonamide derivative and medicinal use thereof
(2S)-2-[[2,6-difluoro-4-[[5-(1,3-thiazol-2-yl)-2-pyridinyl]sulfonylamino]benzoyl]amino]-3-[4-(1-methyl-2,4-dioxo-4aH-pyrido[3,4-d]pyrimidin-1-ium-3-yl)phenyl]propanoic acid	IC50	22 nM	US-9533985: Sulfonamide derivative and medicinal use thereof
(2S)-2-[[2,6-difluoro-4-[[5-(triazol-1-yl)-2-pyridinyl]sulfonylamino]benzoyl]amino]-3-[4-(1-methyl-2,4-dioxo-4a,5,6,7,8,8a-hexahydropyrido[3,4-d]pyrimidin-3-yl)phenyl]propanoic acid	IC50	22 nM	US-9533985: Sulfonamide derivative and medicinal use thereof
(2S)-2-[[2,6-difluoro-4-[[4-(1,2,3,6-tetrahydropyridin-4-yl)phenyl]sulfonylamino]benzoyl]amino]-3-[4-(1-methyl-2,4-dioxo-4aH-pyrido[3,4-d]pyrimidin-1-ium-3-yl)phenyl]propanoic acid	IC50	31 nM	US-9533985: Sulfonamide derivative and medicinal use thereof
(2S)-2-[[2,6-difluoro-4-[[6-(1,2,4-triazol-1-yl)-3-pyridinyl]sulfonylamino]benzoyl]amino]-3-[4-(1-methyl-2,4-dioxo-4aH-pyrido[3,4-d]pyrimidin-1-ium-3-yl)phenyl]propanoic acid	IC50	45 nM	US-9533985: Sulfonamide derivative and medicinal use thereof
(2S)-2-[[2,6-difluoro-4-[(6-pyridin-4-yl-3-pyridinyl)sulfonylamino]benzoyl]amino]-3-[4-(1-methyl-2,4-dioxo-4aH-pyrido[3,4-d]pyrimidin-1-ium-3-yl)phenyl]propanoic acid	IC50	52 nM	US-9533985: Sulfonamide derivative and medicinal use thereof
(2S)-2-[[2,6-difluoro-4-[(4-pyrazol-1-ylphenyl)sulfonylamino]benzoyl]amino]-3-[4-(1-methyl-2,4-dioxo-4aH-pyrido[3,4-d]pyrimidin-1-ium-3-yl)phenyl]propanoic acid	IC50	100 nM	US-9533985: Sulfonamide derivative and medicinal use thereof
(2S)-2-[[2,6-difluoro-4-[[4-(2-fluoro-4-pyridinyl)phenyl]sulfonylamino]benzoyl]amino]-3-[4-(1-methyl-2,4-dioxo-4a,5,6,7,8,8a-hexahydropyrido[3,4-d]pyrimidin-3-yl)phenyl]propanoic acid	IC50	120 nM	US-9533985: Sulfonamide derivative and medicinal use thereof
(2S)-2-[[2,6-difluoro-4-[(4-pyrimidin-2-ylphenyl)sulfonylamino]benzoyl]amino]-3-[4-(1-methyl-2,4-dioxo-4aH-pyrido[3,4-d]pyrimidin-1-ium-3-yl)phenyl]propanoic acid	IC50	130 nM	US-9533985: Sulfonamide derivative and medicinal use thereof
(2S)-2-[[2-fluoro-4-(pyridin-4-ylsulfonylamino)benzoyl]amino]-3-[4-(1-methyl-2,4-dioxo-4a,5,6,7,8,8a-hexahydropyrido[3,4-d]pyrimidin-3-yl)phenyl]propanoic acid	IC50	140 nM	US-9533985: Sulfonamide derivative and medicinal use thereof
(2S)-2-[[2,6-difluoro-4-[[4-(triazol-2-yl)phenyl]sulfonylamino]benzoyl]amino]-3-[4-(1-methyl-2,4-dioxo-4aH-pyrido[3,4-d]pyrimidin-1-ium-3-yl)phenyl]propanoic acid	IC50	150 nM	US-9533985: Sulfonamide derivative and medicinal use thereof
(2S)-2-[[2,6-difluoro-4-[(4-pyrimidin-2-ylphenyl)sulfonylamino]benzoyl]amino]-3-[4-(3,7-dimethyl-2,6-dioxo-4,5-dihydropurin-1-yl)phenyl]propanoic acid	IC50	150 nM	US-9533985: Sulfonamide derivative and medicinal use thereof
(2S)-2-[[4-[[4-(ethylcarbamoyl)phenyl]sulfonylamino]-2,6-difluorobenzoyl]amino]-3-[4-(3-methyl-2,6-dioxo-1,3-diazinan-1-yl)phenyl]propanoic acid	IC50	160 nM	US-9533985: Sulfonamide derivative and medicinal use thereof
(2S)-2-[[2,6-difluoro-4-[[5-(1,2,4-triazol-1-yl)-2-pyridinyl]sulfonylamino]benzoyl]amino]-3-[4-(3-methyl-2,6-dioxo-1,3-diazinan-1-yl)phenyl]propanoic acid	IC50	160 nM	US-9533985: Sulfonamide derivative and medicinal use thereof
(2S)-2-[[2,6-difluoro-4-[[4-(6-methyl-3-pyridinyl)phenyl]sulfonylamino]benzoyl]amino]-3-[4-(1-methyl-2,4-dioxo-4a,5,6,7,8,8a-hexahydropyrido[3,4-d]pyrimidin-3-yl)phenyl]propanoic acid	IC50	180 nM	US-9533985: Sulfonamide derivative and medicinal use thereof
(2S)-2-[[2,6-difluoro-4-[(4-pyrimidin-2-ylphenyl)sulfonylamino]benzoyl]amino]-3-[4-(6-methoxy-1-methyl-2,4-dioxo-4a,5,6,7,8,8a-hexahydropyrido[3,4-d]pyrimidin-3-yl)phenyl]propanoic acid	IC50	200 nM	US-9533985: Sulfonamide derivative and medicinal use thereof
(2S)-2-[[2,6-difluoro-4-[(4-pyridin-4-ylphenyl)sulfonylamino]benzoyl]amino]-3-[4-(1-methyl-2,4-dioxo-4a,5,6,7,8,8a-hexahydropyrido[3,4-d]pyrimidin-3-yl)phenyl]propanoic acid	IC50	210 nM	US-9533985: Sulfonamide derivative and medicinal use thereof
(2S)-2-[[2,6-difluoro-4-[(4-pyrrol-1-ylphenyl)sulfonylamino]benzoyl]amino]-3-[4-(1-methyl-2,4-dioxo-4aH-pyrido[3,4-d]pyrimidin-1-ium-3-yl)phenyl]propanoic acid	IC50	220 nM	US-9533985: Sulfonamide derivative and medicinal use thereof
(2S)-2-[[4-[[4-(2,6-dimethyl-4-pyridinyl)phenyl]sulfonylamino]-2,6-difluorobenzoyl]amino]-3-[4-(1-methyl-2,4-dioxo-4a,5,6,7,8,8a-hexahydropyrido[3,4-d]pyrimidin-3-yl)phenyl]propanoic acid	IC50	270 nM	US-9533985: Sulfonamide derivative and medicinal use thereof
(2S)-2-[[2,6-difluoro-4-[[4-(furan-3-yl)phenyl]sulfonylamino]benzoyl]amino]-3-[4-(1-methyl-2,4-dioxo-4aH-pyrido[3,4-d]pyrimidin-1-ium-3-yl)phenyl]propanoic acid	IC50	280 nM	US-9533985: Sulfonamide derivative and medicinal use thereof
(2S)-2-[[2,6-difluoro-4-[(4-pyridin-4-ylphenyl)sulfonylamino]benzoyl]amino]-3-[4-(3,7-dimethyl-2,6-dioxo-4,5-dihydropurin-1-yl)phenyl]propanoic acid	IC50	310 nM	US-9533985: Sulfonamide derivative and medicinal use thereof
(2S)-2-[[2,6-difluoro-4-[[4-(2-methyl-4-pyridinyl)phenyl]sulfonylamino]benzoyl]amino]-3-[4-(1-methyl-2,4-dioxo-4a,5,6,7,8,8a-hexahydropyrido[3,4-d]pyrimidin-3-yl)phenyl]propanoic acid	IC50	330 nM	US-9533985: Sulfonamide derivative and medicinal use thereof
(2S)-2-[[2,6-difluoro-4-[[4-(1,2,4-triazol-1-yl)phenyl]sulfonylamino]benzoyl]amino]-3-[4-[6-(dimethylamino)-1-methyl-2,4-dioxo-4a,5,6,7,8,8a-hexahydroquinazolin-3-yl]phenyl]propanoic acid	IC50	340 nM	US-9533985: Sulfonamide derivative and medicinal use thereof
(2S)-2-[[4-[[4-(cyclopropylcarbamoyl)phenyl]sulfonylamino]-2,6-difluorobenzoyl]amino]-3-[4-(6-methoxy-1-methyl-2,4-dioxo-4aH-quinazolin-1-ium-3-yl)phenyl]propanoic acid	IC50	370 nM	US-9533985: Sulfonamide derivative and medicinal use thereof
(2S)-2-[[2,6-difluoro-4-[[5-(triazol-2-yl)-2-pyridinyl]sulfonylamino]benzoyl]amino]-3-[4-(3-methyl-2,6-dioxo-1,3-diazinan-1-yl)phenyl]propanoic acid	IC50	400 nM	US-9533985: Sulfonamide derivative and medicinal use thereof
(2S)-2-[[2,6-difluoro-4-[[4-(triazol-1-yl)phenyl]sulfonylamino]benzoyl]amino]-3-[4-(3-methyl-2,6-dioxo-1,3-diazinan-1-yl)phenyl]propanoic acid	IC50	410 nM	US-9533985: Sulfonamide derivative and medicinal use thereof
(2S)-2-[[2,6-difluoro-4-[[5-(triazol-1-yl)-2-pyridinyl]sulfonylamino]benzoyl]amino]-3-[4-(3-methyl-2,6-dioxo-1,3-diazinan-1-yl)phenyl]propanoic acid	IC50	410 nM	US-9533985: Sulfonamide derivative and medicinal use thereof
(2S)-2-[[2,6-difluoro-4-[[4-(3-methyl-4-pyridinyl)phenyl]sulfonylamino]benzoyl]amino]-3-[4-(1-methyl-2,4-dioxo-4aH-pyrido[3,4-d]pyrimidin-1-ium-3-yl)phenyl]propanoic acid	IC50	420 nM	US-9533985: Sulfonamide derivative and medicinal use thereof
(2S)-2-[[2,6-difluoro-4-[(5-pyrimidin-5-yl-2-pyridinyl)sulfonylamino]benzoyl]amino]-3-[4-(3-methyl-2,6-dioxo-1,3-diazinan-1-yl)phenyl]propanoic acid	IC50	480 nM	US-9533985: Sulfonamide derivative and medicinal use thereof
(2S)-2-[[2,6-difluoro-4-[[4-(2-methyl-4-pyridinyl)phenyl]sulfonylamino]benzoyl]amino]-3-[4-(3,7-dimethyl-2,6-dioxo-4,5-dihydropurin-1-yl)phenyl]propanoic acid	IC50	520 nM	US-9533985: Sulfonamide derivative and medicinal use thereof
BDBM260664	IC50	550 nM	US-9533985: Sulfonamide derivative and medicinal use thereof
(2S)-2-[[2,6-difluoro-4-[(4-pyrrol-1-ylphenyl)sulfonylamino]benzoyl]amino]-3-[4-(3,7-dimethyl-2,6-dioxo-4,5-dihydropurin-1-yl)phenyl]propanoic acid	IC50	910 nM	US-9533985: Sulfonamide derivative and medicinal use thereof
(2S)-2-[[2,6-difluoro-4-[(4-pyrimidin-5-ylphenyl)sulfonylamino]benzoyl]amino]-3-[4-(3-methyl-2,6-dioxo-1,3-diazinan-1-yl)phenyl]propanoic acid	IC50	1200 nM	US-9533985: Sulfonamide derivative and medicinal use thereof
(2S)-2-[[2,6-difluoro-4-[[4-(triazol-1-yl)phenyl]sulfonylamino]benzoyl]amino]-3-[4-(6-methoxy-1-methyl-2,4-dioxo-4a,5,6,7,8,8a-hexahydroquinazolin-3-yl)phenyl]propanoic acid	IC50	1500 nM	US-9533985: Sulfonamide derivative and medicinal use thereof
(2S)-2-[[2,6-difluoro-4-[(4-pyrrol-1-ylphenyl)sulfonylamino]benzoyl]amino]-3-[4-(3-methyl-2,6-dioxo-1,3-diazinan-1-yl)phenyl]propanoic acid	IC50	1500 nM	US-9533985: Sulfonamide derivative and medicinal use thereof

ChEMBL bioactivities

68 potent at pChembl≥5 of 107 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.30	IC50	5	nM	CHEMBL119039
8.22	IC50	6	nM	CHEMBL117894
8.15	IC50	7	nM	CHEMBL116070
8.10	IC50	8	nM	CHEMBL116070
7.77	IC50	17	nM	CHEMBL326120
7.72	IC50	19	nM	CHEMBL325184
7.70	IC50	20	nM	CHEMBL117279
7.70	IC50	20	nM	CHEMBL116070
7.64	IC50	23	nM	CHEMBL119183
7.52	IC50	30	nM	CHEMBL117279
7.32	IC50	48	nM	CHEMBL116070
7.19	IC50	64	nM	CHEMBL117936
7.16	IC50	70	nM	CHEMBL118074
7.13	IC50	74	nM	CHEMBL118089
7.10	IC50	79	nM	CHEMBL115637
7.07	IC50	85	nM	CHEMBL117198
7.04	IC50	91	nM	CHEMBL115971
6.92	IC50	120	nM	CHEMBL117279
6.89	IC50	130	nM	CHEMBL324133
6.85	IC50	140	nM	CHEMBL119732
6.77	IC50	170	nM	CHEMBL115431
6.76	IC50	175	nM	CHEMBL6248
6.72	IC50	191	nM	CHEMBL118022
6.70	IC50	200	nM	CHEMBL118074
6.62	IC50	240	nM	CHEMBL119705
6.48	IC50	330	nM	CHEMBL119599
6.43	IC50	370	nM	CHEMBL118300
6.38	IC50	420	nM	CHEMBL115960
6.33	IC50	470	nM	CHEMBL324824
6.11	IC50	770	nM	CHEMBL6830
6.11	IC50	780	nM	CHEMBL325286
6.07	IC50	850	nM	CHEMBL325893
6.06	IC50	880	nM	CHEMBL119523
6.03	IC50	930	nM	CHEMBL115462
5.89	IC50	1300	nM	CHEMBL6257
5.68	IC50	2100	nM	CHEMBL266572
5.64	IC50	2300	nM	CHEMBL266197
5.60	IC50	2500	nM	CHEMBL4166467
5.60	IC50	2500	nM	CHEMBL6229
5.57	IC50	2700	nM	CHEMBL6371
5.52	IC50	3000	nM	CHEMBL53269
5.46	IC50	3500	nM	CHEMBL267127
5.46	IC50	3500	nM	CHEMBL6249
5.41	IC50	3900	nM	CHEMBL118518
5.40	IC50	4000	nM	CHEMBL298775
5.35	IC50	4500	nM	CHEMBL4166036
5.30	IC50	5000	nM	CHEMBL53082
5.30	IC50	5000	nM	CHEMBL52799
5.30	IC50	5000	nM	CHEMBL51654
5.30	IC50	5000	nM	CHEMBL53475

PubChem BioAssay actives

68 with measured affinity, of 212 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-methyl-4-(4-pyrazol-1-ylphenoxy)thieno[2,3-c]pyridine-2-carboxamide	216483: Inhibition of VCAM-1 in human endothelial cells	ic50	0.0050	uM
N-methyl-4-(4-thiophen-2-ylphenoxy)thieno[2,3-c]pyridine-2-carboxamide	216483: Inhibition of VCAM-1 in human endothelial cells	ic50	0.0060	uM
4-(4-bromophenoxy)thieno[2,3-c]pyridine-2-carboxamide	216486: In vitro inhibitory potency compared to IL1-beta induced VCAM-1 in human endothelial cells (ELISA assay)	ic50	0.0070	uM
4-(4-imidazol-1-ylphenoxy)thieno[2,3-c]pyridine-2-carboxamide	216483: Inhibition of VCAM-1 in human endothelial cells	ic50	0.0170	uM
4-(4-imidazol-1-ylphenoxy)-N-methylthieno[2,3-c]pyridine-2-carboxamide	216483: Inhibition of VCAM-1 in human endothelial cells	ic50	0.0190	uM
4-[4-[2-(2-methoxyethoxy)ethoxymethyl]phenoxy]-N-methylthieno[2,3-c]pyridine-2-carboxamide	216486: In vitro inhibitory potency compared to IL1-beta induced VCAM-1 in human endothelial cells (ELISA assay)	ic50	0.0200	uM
4-[4-(methoxymethyl)phenoxy]thieno[2,3-c]pyridine-2-carboxamide	216483: Inhibition of VCAM-1 in human endothelial cells	ic50	0.0230	uM
4-(4-aminophenoxy)thieno[2,3-c]pyridine-2-carboxamide	216483: Inhibition of VCAM-1 in human endothelial cells	ic50	0.0640	uM
4-(4-chlorophenoxy)-N-methylthieno[2,3-c]pyridine-2-carboxamide	216485: In vitro inhibitory potency compared to IL1-beta induced VCAM-1 expression in human endothelial cells (ELISA assay)	ic50	0.0700	uM
4-[4-[1-(hydroxymethyl)cyclopropyl]phenoxy]-N-methylthieno[2,3-c]pyridine-2-carboxamide	216483: Inhibition of VCAM-1 in human endothelial cells	ic50	0.0740	uM
N-methyl-4-(4-phenylphenoxy)thieno[2,3-c]pyridine-2-carboxamide	216483: Inhibition of VCAM-1 in human endothelial cells	ic50	0.0790	uM
4-(4-cyanophenoxy)thieno[2,3-c]pyridine-2-carboxamide	216483: Inhibition of VCAM-1 in human endothelial cells	ic50	0.0850	uM
4-(4-cyanophenoxy)-N-methylthieno[2,3-c]pyridine-2-carboxamide	216483: Inhibition of VCAM-1 in human endothelial cells	ic50	0.0910	uM
4-(4-chlorophenoxy)-N,N-dimethylthieno[2,3-c]pyridine-2-carboxamide	216483: Inhibition of VCAM-1 in human endothelial cells	ic50	0.1300	uM
4-(4-ethylphenoxy)thieno[2,3-c]pyridine-2-carboxamide	216483: Inhibition of VCAM-1 in human endothelial cells	ic50	0.1400	uM
4-[4-[2-[2-(2-ethoxyethoxy)ethoxy]-1,1-difluoroethyl]phenoxy]-N-methylthieno[2,3-c]pyridine-2-carboxamide	216483: Inhibition of VCAM-1 in human endothelial cells	ic50	0.1700	uM
5-methoxy-3-propan-2-yloxy-1-benzothiophene-2-carboxamide	216491: In vitro potency against TNF alpha induced expression of VCAM-1 on human vascular endothelial cells using CAM ELISA assay	ic50	0.1750	uM
4-[4-(hydroxymethyl)phenoxy]thieno[2,3-c]pyridine-2-carboxamide	216483: Inhibition of VCAM-1 in human endothelial cells	ic50	0.1910	uM
N-methyl-4-[4-(1,2,4-triazol-1-yl)phenoxy]thieno[2,3-c]pyridine-2-carboxamide	216483: Inhibition of VCAM-1 in human endothelial cells	ic50	0.2400	uM
4-(2-bromo-4-chlorophenoxy)thieno[2,3-c]pyridine-2-carboxamide	216483: Inhibition of VCAM-1 in human endothelial cells	ic50	0.3300	uM
N-methyl-4-[4-(trifluoromethoxy)phenoxy]thieno[2,3-c]pyridine-2-carboxamide	216483: Inhibition of VCAM-1 in human endothelial cells	ic50	0.3700	uM
4-[4-[1-[2-(2-ethoxyethoxy)ethoxymethyl]cyclopropyl]phenoxy]-N-methylthieno[2,3-c]pyridine-2-carboxamide	216483: Inhibition of VCAM-1 in human endothelial cells	ic50	0.4200	uM
4-[4-(1,1-difluoro-2-hydroxyethyl)phenoxy]-N-methylthieno[2,3-c]pyridine-2-carboxamide	216483: Inhibition of VCAM-1 in human endothelial cells	ic50	0.4700	uM
4-(2,4-dimethylphenyl)sulfanylthieno[2,3-c]pyridine-2-carboxamide	216491: In vitro potency against TNF alpha induced expression of VCAM-1 on human vascular endothelial cells using CAM ELISA assay	ic50	0.7700	uM
4-(2-prop-2-enylphenoxy)thieno[2,3-c]pyridine-2-carboxamide	216483: Inhibition of VCAM-1 in human endothelial cells	ic50	0.7800	uM
4-(3-chlorophenoxy)thieno[2,3-c]pyridine-2-carboxamide	216483: Inhibition of VCAM-1 in human endothelial cells	ic50	0.8500	uM
4-(4-chlorophenoxy)-N-(2-hydroxyethyl)thieno[2,3-c]pyridine-2-carboxamide	216483: Inhibition of VCAM-1 in human endothelial cells	ic50	0.8800	uM
4-[4-(1,2-dihydroxyethyl)phenoxy]thieno[2,3-c]pyridine-2-carboxamide	216483: Inhibition of VCAM-1 in human endothelial cells	ic50	0.9300	uM
4-chlorothieno[2,3-c]pyridine-2-carboxamide	216491: In vitro potency against TNF alpha induced expression of VCAM-1 on human vascular endothelial cells using CAM ELISA assay	ic50	1.3000	uM
4-(4-methylphenyl)sulfanylthieno[2,3-c]pyridine	216491: In vitro potency against TNF alpha induced expression of VCAM-1 on human vascular endothelial cells using CAM ELISA assay	ic50	2.1000	uM
2-ethyl-4-(4-methylphenyl)sulfanylthieno[2,3-c]pyridine	216491: In vitro potency against TNF alpha induced expression of VCAM-1 on human vascular endothelial cells using CAM ELISA assay	ic50	2.3000	uM
2-[3-(10H-pyrazino[2,3-b][1,4]benzothiazin-8-ylmethyl)-3-azabicyclo[3.3.1]nonan-9-yl]acetic acid	1508013: Inhibition of VCAM1 (unknown origin)	ic50	2.5000	uM
5-(6-ethylthieno[2,3-d]pyrimidin-4-yl)sulfanyl-1,3,4-thiadiazol-2-amine	216491: In vitro potency against TNF alpha induced expression of VCAM-1 on human vascular endothelial cells using CAM ELISA assay	ic50	2.5000	uM
[4-(4-methylphenyl)sulfanylthieno[2,3-c]pyridin-2-yl]-phenylmethanone	216491: In vitro potency against TNF alpha induced expression of VCAM-1 on human vascular endothelial cells using CAM ELISA assay	ic50	2.7000	uM
4-chloro-N,N-diethyl-3-nitrobenzenesulfonamide	216481: Ability to inhibit expression of Vascular cell adhesion molecule 1	ic50	3.0000	uM
(E)-1-[4-(4-methylphenyl)sulfanylthieno[2,3-c]pyridin-2-yl]-N-phenoxymethanimine	216491: In vitro potency against TNF alpha induced expression of VCAM-1 on human vascular endothelial cells using CAM ELISA assay	ic50	3.5000	uM
6-ethyl-4-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]thieno[2,3-d]pyrimidine	216491: In vitro potency against TNF alpha induced expression of VCAM-1 on human vascular endothelial cells using CAM ELISA assay	ic50	3.5000	uM
4-(4-chlorophenoxy)thieno[2,3-c]pyridine-2-carboxamide	216483: Inhibition of VCAM-1 in human endothelial cells	ic50	3.9000	uM
1-(4-chloro-3-nitrophenyl)sulfonylpyrrolidine	216481: Ability to inhibit expression of Vascular cell adhesion molecule 1	ic50	4.0000	uM
8-[[4-(dimethylsulfamoylamino)piperidin-1-yl]methyl]-10H-pyrazino[2,3-b][1,4]benzothiazine	1508013: Inhibition of VCAM1 (unknown origin)	ic50	4.5000	uM
bis(4-chloro-3-nitrophenyl)methanone	216481: Ability to inhibit expression of Vascular cell adhesion molecule 1	ic50	5.0000	uM
4-chloro-N,N-bis(2-methoxyethyl)-3-nitrobenzenesulfonamide	216481: Ability to inhibit expression of Vascular cell adhesion molecule 1	ic50	5.0000	uM
methyl 4-methylsulfonyl-3-nitrobenzoate	216481: Ability to inhibit expression of Vascular cell adhesion molecule 1	ic50	5.0000	uM
4-chloro-2-nitrobenzonitrile	216481: Ability to inhibit expression of Vascular cell adhesion molecule 1	ic50	5.0000	uM
4-[2,6-ditert-butyl-4-[2-(3,5-ditert-butyl-4-hydroxyphenyl)sulfanylpropan-2-ylsulfanyl]phenoxy]-4-oxobutanoic acid	216494: Inhibition of TNF-alpha inducible Vascular cell adhesion molecule-1 expression.	ic50	6.0000	uM
4-chloro-N-[3-[(4-chloro-3-nitrophenyl)sulfonyl-methylamino]propyl]-N-methyl-3-nitrobenzenesulfonamide	216481: Ability to inhibit expression of Vascular cell adhesion molecule 1	ic50	6.0000	uM
4-chloro-N-(4-chloro-3-nitrophenyl)sulfonyl-3-nitro-N-phenylbenzenesulfonamide	216481: Ability to inhibit expression of Vascular cell adhesion molecule 1	ic50	7.0000	uM
4-chloro-3-nitro-N,N-dipentylbenzenesulfonamide	216481: Ability to inhibit expression of Vascular cell adhesion molecule 1	ic50	7.0000	uM
1-fluoro-4-(4-fluoro-3-nitrophenyl)sulfonyl-2-nitrobenzene	216481: Ability to inhibit expression of Vascular cell adhesion molecule 1	ic50	7.0000	uM
1-(4-chloro-3-nitrophenyl)sulfonyl-4-methylpiperazine	216481: Ability to inhibit expression of Vascular cell adhesion molecule 1	ic50	8.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Lipopolysaccharides	decreases reaction, increases expression, increases reaction, increases secretion, affects reaction	17
Particulate Matter	increases abundance, affects expression, affects reaction, decreases expression, decreases reaction (+1 more)	12
Vehicle Emissions	decreases reaction, increases abundance, increases expression, increases reaction, affects expression (+1 more)	9
Glucose	decreases reaction, increases expression, affects cotreatment, increases secretion	8
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases expression	8
Simvastatin	decreases reaction, increases expression, affects cotreatment, decreases expression, increases reaction	8
Quercetin	affects cotreatment, decreases reaction, increases expression, increases reaction	6
bisphenol A	affects cotreatment, decreases reaction, increases expression, decreases expression	5
3-(4-methylphenylsulfonyl)-2-propenenitrile	increases expression, affects binding, increases reaction, increases abundance, decreases reaction	5
lipopolysaccharide, Escherichia coli O111 B4	decreases reaction, increases expression, affects reaction	5
Resveratrol	decreases reaction, increases expression, decreases expression	5
Acetylcysteine	decreases reaction, increases expression	5
Hydrogen Peroxide	decreases reaction, increases secretion, increases expression, decreases expression	5
Ascorbic Acid	decreases reaction, decreases expression, affects binding, affects cotreatment, increases expression	4
Plant Extracts	increases reaction, decreases expression, decreases reaction, increases expression	4
titanium dioxide	decreases reaction, increases expression	3
acetovanillone	decreases reaction, increases expression	3
SB 203580	increases expression, decreases reaction	3
lipopolysaccharide, E coli O55-B5	decreases reaction, increases expression, affects cotreatment	3
Air Pollutants	affects expression, increases expression, affects reaction	3
Arsenic	increases expression, increases secretion	3
Dexamethasone	decreases reaction, increases expression, decreases expression, affects cotreatment	3
Estradiol	decreases reaction, increases expression, affects cotreatment, decreases expression	3
Ethinyl Estradiol	increases reaction, affects cotreatment, decreases expression	3
Formaldehyde	decreases expression, increases expression	3
Hydrocortisone	affects cotreatment, increases expression, decreases reaction	3
Sulfasalazine	decreases reaction, increases expression, decreases expression	3
Smoke	increases expression, decreases reaction	3
Tetrachlorodibenzodioxin	affects expression, decreases expression, increases expression	3
Soot	increases expression	3

ChEMBL screening assays

16 unique, capped per target: 15 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1176151	Binding	Inhibition of VCAM1 in TNF-alpha/IL4-stimulated HUVEC assessed as inhibition of cell adhesion between HUVEC and Ramos cells at 8 uM after 20 hrs incubation relative to untreated control	Symbiopolyol, a VCAM-1 inhibitor from a symbiotic dinoflagellate of the jellyfish Mastigias papua. — J Nat Prod
CHEMBL815903	Functional	Inhibition of TNF-alpha inducible Vascular cell adhesion molecule-1 expression.	Novel phenolic antioxidants as multifunctional inhibitors of inducible VCAM-1 expression for use in atherosclerosis. — Bioorg Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1IG	Abcam A-549 VCAM1 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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