General Information of the Protein
Protein ID
PT01186
Protein Name
Integrin alpha-4
Secondarily
Protein Name
CD49 antigen-like family member D
Integrin alpha-IV
VLA-4 subunit alpha
Gene Name
ITGA4
Secondarily
Gene Name
CD49D
Sequence
MAWEARREPGPRRAAVRETVMLLLCLGVPTGRPYNVDTESALLYQGPHNTLFGYSVVLHSHGANRWLLVGAPTANWLANASVINPGAIYRCRIGKNPGQTCEQLQLGSPNGEPCGKTCLEERDNQWLGVTLSRQPGENGSIVTCGHRWKNIFYIKNENKLPTGGCYGVPPDLRTELSKRIAPCYQDYVKKFGENFASCQAGISSFYTKDLIVMGAPGSSYWTGSLFVYNITTNKYKAFLDKQNQVKFGSYLGYSVGAGHFRSQHTTEVVGGAPQHEQIGKAYIFSIDEKELNILHEMKGKKLGSYFGASVCAVDLNADGFSDLLVGAPMQSTIREEGRVFVYINSGSGAVMNAMETNLVGSDKYAARFGESIVNLGDIDNDGFEDVAIGAPQEDDLQGAIYIYNGRADGISSTFSQRIEGLQISKSLSMFGQSISGQIDADNNGYVDVAVGAFRSDSAVLLRTRPVVIVDASLSHPESVNRTKFDCVENGWPSVCIDLTLCFSYKGKEVPGYIVLFYNMSLDVNRKAESPPRFYFSSNGTSDVITGSIQVSSREANCRTHQAFMRKDVRDILTPIQIEAAYHLGPHVISKRSTEEFPPLQPILQQKKEKDIMKKTINFARFCAHENCSADLQVSAKIGFLKPHENKTYLAVGSMKTLMLNVSLFNAGDDAYETTLHVKLPVGLYFIKILELEEKQINCEVTDNSGVVQLDCSIGYIYVDHLSRIDISFLLDVSSLSRAEEDLSITVHATCENEEEMDNLKHSRVTVAIPLKYEVKLTVHGFVNPTSFVYGSNDENEPETCMVEKMNLTFHVINTGNSMAPNVSVEIMVPNSFSPQTDKLFNILDVQTTTGECHFENYQRVCALEQQKSAMQTLKGIVRFLSKTDKRLLYCIKADPHCLNFLCNFGKMESGKEASVHIQLEGRPSILEMDETSALKFEIRATGFPEPNPRVIELNKDENVAHVLLEGLHHQRPKRYFTIVIISSSLLLGLIVLLLISYVMWKAGFFKRQYKSILQEENRRDSWSYINSKSNDD
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Organism
Homo sapiens, Human
Protein Classification
Membrane receptor
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 (PubMed:23125415). 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 (PubMed:18635536, PubMed:25398877). 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 (PubMed:35802072).
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Uniprot ID
Primary ID:
P13612

Secondarily ID:
D3DPG4
Q7Z4L6
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HGNC ID
HGNC:6140
Subcellular Location
Membrane
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000026 , CHO-K1
Compound ID Compound Name Compound Formula
CP0000189
4-{[(2S,4S)-1-[2-(3-chloro-4-{[(2-methylphenyl)carbamoyl]amino}phenyl)acetyl]-4-fluoropyrrolidin-2-yl]methoxy}benzoic acid
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C28H27ClFN3O5
 2
1
IC50 = 0.51 nM
   TI
   LI
   LO
   TS
2
IC50 = 7.2 nM
   TI
   LI
   LO
   TS
CP0112732
4-{[(2S,4S)-1-[2-(3-bromo-4-{[(2-methylphenyl)carbamoyl]amino}phenyl)acetyl]-4-fluoropyrrolidin-2-yl]methoxy}benzoic acid
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C28H27BrFN3O5
 2
1
IC50 = 0.78 nM
   TI
   LI
   LO
   TS
2
IC50 = 8.4 nM
   TI
   LI
   LO
   TS
CP0346334
4-{[(2S,4S)-1-[2-(4-{[(2-chlorophenyl)carbamoyl]amino}-3-methoxyphenyl)acetyl]-4-fluoropyrrolidin-2-yl]methoxy}benzoic acid
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C28H27ClFN3O6
 2
1
IC50 = 0.87 nM
   TI
   LI
   LO
   TS
2
IC50 = 6.2 nM
   TI
   LI
   LO
   TS
CP0511029
4-{[(2S,4S)-4-fluoro-1-[2-(3-methoxy-4-{[(2-methylphenyl)carbamoyl]amino}phenyl)acetyl]pyrrolidin-2-yl]methoxy}benzoic acid
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C29H30FN3O6
 2
1
IC50 = 1.2 nM
   TI
   LI
   LO
   TS
2
IC50 = 3.7 nM
   TI
   LI
   LO
   TS
CP0112731
4-{[(2S,4S)-1-[2-(3-bromo-4-{[(2-chlorophenyl)carbamoyl]amino}phenyl)acetyl]-4-fluoropyrrolidin-2-yl]methoxy}benzoic acid
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C27H24BrClFN3O5
 2
1
IC50 = 1.3 nM
   TI
   LI
   LO
   TS
2
IC50 = 51 nM
   TI
   LI
   LO
   TS
CP0346336
4-{[(2S,4S)-1-[2-(3-chloro-4-{[(2-chlorophenyl)carbamoyl]amino}phenyl)acetyl]-4-fluoropyrrolidin-2-yl]methoxy}benzoic acid
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C27H24Cl2FN3O5
 2
1
IC50 = 1.3 nM
   TI
   LI
   LO
   TS
2
IC50 = 81 nM
   TI
   LI
   LO
   TS
CP0276640
4-{[(2S,4S)-1-[2-(3-bromo-4-{[(2-bromophenyl)carbamoyl]amino}phenyl)acetyl]-4-fluoropyrrolidin-2-yl]methoxy}benzoic acid
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C27H24Br2FN3O5
 2
1
IC50 = 1.4 nM
   TI
   LI
   LO
   TS
2
IC50 = 95 nM
   TI
   LI
   LO
   TS
CP0346333
4-{[(2S,4S)-1-[2-(4-{[(2-bromophenyl)carbamoyl]amino}-3-methoxyphenyl)acetyl]-4-fluoropyrrolidin-2-yl]methoxy}benzoic acid
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C28H27BrFN3O6
 2
1
IC50 = 1.6 nM
   TI
   LI
   LO
   TS
2
IC50 = 16 nM
   TI
   LI
   LO
   TS
CP0062222
4-{[(2S,4S)-1-[2-(4-{[(2-bromophenyl)carbamoyl]amino}-3-chlorophenyl)acetyl]-4-fluoropyrrolidin-2-yl]methoxy}benzoic acid
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C27H24BrClFN3O5
 2
1
IC50 = 1.7 nM
   TI
   LI
   LO
   TS
2
IC50 = 137 nM
   TI
   LI
   LO
   TS
CP0112733
4-{[(2S,4S)-4-fluoro-1-[2-(3-methyl-4-{[(2-methylphenyl)carbamoyl]amino}phenyl)acetyl]pyrrolidin-2-yl]methoxy}benzoic acid
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C29H30FN3O5
 2
1
IC50 = 2.3 nM
   TI
   LI
   LO
   TS
2
IC50 = 49 nM
   TI
   LI
   LO
   TS
CP0000190
4-[[(2S,4S)-4-fluoro-1-[2-[2-(2-methylanilino)-1,3-benzoxazol-6-yl]acetyl]pyrrolidin-2-yl]methoxy]cyclohexane-1-carboxylic acid
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C28H32FN3O5
 1
1
IC50 = 2.8 nM
   TI
   LI
   LO
   TS
CP0306021
4-{[(2S,4S)-4-fluoro-1-[2-(3-methoxy-4-{[(2-methoxyphenyl)carbamoyl]amino}phenyl)acetyl]pyrrolidin-2-yl]methoxy}benzoic acid
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C29H30FN3O7
 2
1
IC50 = 9.2 nM
   TI
   LI
   LO
   TS
2
IC50 = 268 nM
   TI
   LI
   LO
   TS
CP0442128
4-{[(2S,4S)-1-[2-(4-{[(2-bromophenyl)carbamoyl]amino}-3-methylphenyl)acetyl]-4-fluoropyrrolidin-2-yl]methoxy}benzoic acid
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C28H27BrFN3O5
 2
1
IC50 = 9.8 nM
   TI
   LI
   LO
   TS
2
IC50 = 622 nM
   TI
   LI
   LO
   TS
CP0171979
4-{[(2S,4S)-1-[2-(4-{[(2-chlorophenyl)carbamoyl]amino}-3-methylphenyl)acetyl]-4-fluoropyrrolidin-2-yl]methoxy}benzoic acid
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C28H27ClFN3O5
 2
1
IC50 = 13 nM
   TI
   LI
   LO
   TS
2
IC50 = 416 nM
   TI
   LI
   LO
   TS
CP0369218
4-{[(2S,4S)-1-[2-(3-ethyl-4-{[(2-methylphenyl)carbamoyl]amino}phenyl)acetyl]-4-fluoropyrrolidin-2-yl]methoxy}benzoic acid
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C30H32FN3O5
 2
1
IC50 = 15 nM
   TI
   LI
   LO
   TS
2
IC50 = 282 nM
   TI
   LI
   LO
   TS
CP0502974
4-{[(2S,4S)-4-fluoro-1-[2-(4-{[(2-methylphenyl)carbamoyl]amino}-3-(trifluoromethyl)phenyl)acetyl]pyrrolidin-2-yl]methoxy}benzoic acid
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C29H27F4N3O5
 2
1
IC50 = 15 nM
   TI
   LI
   LO
   TS
2
IC50 = 486 nM
   TI
   LI
   LO
   TS
CP0530335
4-[[2-(2-Methylphenylamino)-6-benzoxazolylacetyl]-(4S)-fluoro-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylic acid
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C28H32FN3O5
 1
1
IC50 = 15 nM
   TI
   LI
   LO
   TS
CP0490685
1-[(4S)-Fluoro-1-[2-(2-methylphenylamino)-6-benzoxazolylacetyl]-(2S)-pyrrolidinylcarbonyl]-4-piperidinylacetic acid
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C28H31FN4O5
 1
1
IC50 = 19 nM
   TI
   LI
   LO
   TS
CP0535344
4-[(4S)-fluoro-1-[2-(2-methylphenylamino)-6-benzoxazolylacetyl]-(2S)-pyrrolidinylmethoxy]benzoic acid
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C28H26FN3O5
 1
1
IC50 = 19 nM
   TI
   LI
   LO
   TS
CP0505328
4-[(4S)-Fluoro-1-[2-(2-methylphenylamino)-6-benzoxazolylacetyl]-(2S)-pyrrolidinylcarbonyl]-1-piperazinylacetic acid
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C27H30FN5O5
 1
1
IC50 = 50 nM
   TI
   LI
   LO
   TS
CP0309463
4-{[(2S,4S)-4-fluoro-1-{2-[3-methoxy-4-({[2-(trifluoromethyl)phenyl]carbamoyl}amino)phenyl]acetyl}pyrrolidin-2-yl]methoxy}benzoic acid
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C29H27F4N3O6
 2
1
IC50 = 106 nM
   TI
   LI
   LO
   TS
2
IC50 > 1000 nM
   TI
   LI
   LO
   TS
CP0522744
6-[(4S)-Fluoro-1-[2-(2-methylphenyl)amino-6-benzoxazolylacetyl]-(2S)-pyrrolidinylmethoxy]hexanoic acid
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C27H32FN3O5
 1
1
IC50 = 164 nM
   TI
   LI
   LO
   TS
CP0535345
5-[(4S)-Fluoro-1-[2-(2-methylphenyl)amino-6-benzoxazolylacetyl]-(2S)-pyrrolidinylmethoxy]pentanoic acid
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C26H30FN3O5
 1
1
IC50 = 198 nM
   TI
   LI
   LO
   TS
CP0551829
4-{[(2S,4S)-4-fluoro-1-[2-(4-{[(2-methylphenyl)carbamoyl]amino}-3-(propan-2-yl)phenyl)acetyl]pyrrolidin-2-yl]methoxy}benzoic acid
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C31H34FN3O5
 2
1
IC50 = 216 nM
   TI
   LI
   LO
   TS
2
IC50 > 1000 nM
   TI
   LI
   LO
   TS
CP0437942
4-[[(2S,4S)-4-fluoro-1-[2-[2-(2-methylanilino)-1,3-benzoxazol-6-yl]acetyl]pyrrolidin-2-yl]methoxy]cyclohexane-1-carboxylic acid
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C28H32FN3O5
 1
1
IC50 = 443 nM
   TI
   LI
   LO
   TS
CP0334956
4-{[(2S,4S)-4-fluoro-1-{2-[3-methoxy-4-({[2-(propan-2-yl)phenyl]carbamoyl}amino)phenyl]acetyl}pyrrolidin-2-yl]methoxy}benzoic acid
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C31H34FN3O6
 2
1
IC50 = 769 nM
   TI
   LI
   LO
   TS
2
IC50 > 1000 nM
   TI
   LI
   LO
   TS
CP0489402
4-[(4S)-fluoro-1-[2-(2-methylphenylamino)-6-benzoxazolylacetyl]-(2S)-pyrrolidinylmethoxy]butanoic acid
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C25H28FN3O5
 1
1
IC50 = 831 nM
   TI
   LI
   LO
   TS
Biochemical Assays
Compound ID Compound Name Compound Formula
CP0063957
(8R,13R)-13-[(S)-2-Amino-3-(4-hydroxy-phenyl)-propionylamino]-6,14-dioxo-10,11-dithia-7,15-diaza-spiro[4.12]heptadecane-8-carboxylic acid
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C23H32N4O6S2
 1
1 IC50 = 0.5 nM
CP0348558
(8R,13R)-13-[(S)-2-Acetylamino-3-(4-hydroxy-phenyl)-propionylamino]-6,14-dioxo-10,11-dithia-7,15-diaza-spiro[4.12]heptadecane-8-carboxylic acid
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C25H34N4O7S2
 1
1 IC50 = 0.7 nM
CP0261092
(5R,8S,13S,15aR)-8-[(S)-2-Acetylamino-3-(4-hydroxy-phenyl)-propionylamino]-5-carboxymethyl-4,7,15-trioxo-tetradecahydro-10,11-dithia-3a,6,14-triaza-cyclopentacyclotetradecene-13-carboxylic acid
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C26H33N5O10S2
 1
1 IC50 = 1.8 nM
CP0448248
(8R,13R)-13-[(S)-2-Amino-3-(4-hydroxy-phenyl)-propionylamino]-6,14-dioxo-10,11-dithia-7,15-diaza-spiro[4.13]octadecane-8-carboxylic acid
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C24H34N4O6S2
 1
1 IC50 = 19 nM
Clinical Information about the Protein
Target 1 ( Integrin alpha-4 (ITGA4) )
Target Type Successful Target
Disease 3 Target-related Diseases  3
1 Asthma [ICD-11: CA23]
2 Inflammatory bowel disease [ICD-11: DD72]
3 Ischemic stroke [ICD-11: 8B11.5Z]
Clinical Trial Drug(s) 3 Clinical Trial Drugs  3
1 BIO-1211 Phase 2
Asthma
2 GSK683699 Phase 2
Inflammatory bowel disease
3 Senktide Phase 2
Ischemic stroke
Target 2 ( ITGA4 messenger RNA (ITGA4 mRNA) )
Target Type Clinical trial Target