Target Information

Target General Infomation
Target ID
T86130
Former ID
TTDI01797
Target Name
Integrin alpha-4/beta-1
Target Type
Clinical Trial
Disease Arthritis [ICD9: 710-719; ICD10: M00-M25]
Asthma [ICD10: J45]
Crohn's disease [ICD9: 555; ICD10: K50]
Inflammatory disease [ICD9: 140-229, 147, 173, 573.3, 710-719; ICD10: C11, C44, K75.9, M00-M25]
Inflammatory bowel disease [ICD9: 555, 556; ICD10: K50, K51]
Multiple scierosis [ICD9: 340; ICD10: G35]
Multiple sclerosis; Rheumatoid arthritis [ICD9: 340, 710-719, 714; ICD10: G35, M00-M25, M05-M06]
Relapsing forms of multiple sclerosis [ICD9: 340; ICD10: G35]
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.
BioChemical Class
Integrin
UniProt ID
P13612||Q8WUM6
Drugs and Mode of Action
Drug(s) AJM-300 Drug Info Phase 3 Crohn's disease [547815]
CDP323 Drug Info Phase 2 Multiple sclerosis; Rheumatoid arthritis [536651]
Firategrast Drug Info Phase 2 Relapsing forms of multiple sclerosis [547712]
R411 Drug Info Phase 2 Asthma [531186]
TRK-170 Drug Info Phase 2 Inflammatory bowel disease [523458]
HMR-1031 Drug Info Phase 1 Arthritis [526984]
TR-14035 Drug Info Discontinued in Phase 1 Multiple scierosis [547053]
CY-9652 Drug Info Terminated Inflammatory disease [546159]
Modulator AJM-300 Drug Info [532326]
CDP323 Drug Info
Firategrast Drug Info
HMR-1031 Drug Info [526984]
R411 Drug Info [531186]
TR-14035 Drug Info
TRK-170 Drug Info [1572591]
Antagonist CY-9652 Drug Info [551906]
Inhibitor TCS2314 Drug Info [543650]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway PI3K-Akt signaling pathway
Focal adhesion
ECM-receptor interaction
Cell adhesion molecules (CAMs)
Hematopoietic cell lineage
Leukocyte transendothelial migration
Intestinal immune network for IgA production
Regulation of actin cytoskeleton
Leishmaniasis
Hypertrophic cardiomyopathy (HCM)
Arrhythmogenic right ventricular cardiomyopathy (ARVC)
Dilated cardiomyopathy
Reactome Elastic fibre formation
Fibronectin matrix formation
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
Cell surface interactions at the vascular wall
Basigin interactions
Molecules associated with elastic fibres
Integrin cell surface interactions
Laminin interactions
Syndecan interactions
ECM proteoglycans
Other semaphorin interactions
Localization of the PINCH-ILK-PARVIN complex to focal adhesions
CHL1 interactions
RHO GTPases Activate Formins
WikiPathways Focal Adhesion
Arrhythmogenic Right Ventricular Cardiomyopathy
Integrin-mediated Cell Adhesion
Integrin cell surface interactions
Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell
Cell surface interactions at the vascular wall
References
Ref 523458ClinicalTrials.gov (NCT01345799) A Study of TRK-170 for the Treatment of Crohn's Disease. U.S. National Institutes of Health.
Ref 526984Pharmacoscintigraphic comparison of HMR 1031, a VLA-4 antagonist, in healthy volunteers following delivery via a nebulizer and a dry powder inhaler. Am J Ther. 2004 Mar-Apr;11(2):103-13.
Ref 531186Integrins as therapeutic targets: lessons and opportunities. Nat Rev Drug Discov. 2010 Oct;9(10):804-20.
Ref 536651Emerging drugs for rheumatoid arthritis. Expert Opin Emerg Drugs. 2008 Mar;13(1):175-96.
Ref 546159Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006649)
Ref 547053Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800012563)
Ref 547712Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800018762)
Ref 547815Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800019529)
Ref
Ref 526984Pharmacoscintigraphic comparison of HMR 1031, a VLA-4 antagonist, in healthy volunteers following delivery via a nebulizer and a dry powder inhaler. Am J Ther. 2004 Mar-Apr;11(2):103-13.
Ref 531186Integrins as therapeutic targets: lessons and opportunities. Nat Rev Drug Discov. 2010 Oct;9(10):804-20.
Ref 532326Oral treatment with a novel small molecule alpha 4 integrin antagonist, AJM300, prevents the development of experimental colitis in mice. J Crohns Colitis. 2013 Dec;7(11):e533-42.
Ref 543650(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2580).
Ref 551906US patent application no. 2010,0278,784, Methods and compositions for treating skin conditions.
Ref 1572591Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.

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