Top ▲

integrin α4β1

Click here for help

Target id: 2580

Nomenclature: integrin α4β1

Family: Integrins

Contents:

Quaternary Structure: Subunits
integrin, alpha 4 subunit (antigen CD49D, alpha 4 subunit of VLA-4 receptor)
integrin, beta 1 subunit (fibronectin receptor, beta polypeptide, antigen CD29 includes MDF2, MSK12)
Previous and Unofficial Names Click here for help
very late antigen-4 | VLA-4
Ligands (Human)
fibronectin (FN1, P02751), vascular cell adhesion protein 1 (VCAM1, P19320), osteopontin (SPP1, P10451), thrombospondin

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
BIO1211 Peptide Hs Inhibition 8.3 – 9.0 pIC50 3
⤷ pIC50 8.3 – 9.0 [3]
carotegrast Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.2 pIC50 4
⤷ pIC50 7.2 (IC50 5.7x10-8 M) [4]
Description: Measuring inhibition of binding between &alpha4;β1 integrin expressed by Jurkat cells and immobilised VCAM-1, in the presence of test compound.
TCS2314 Small molecule or natural product Hs Inhibition - -
⤷
firategrast Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition - - 1
⤷ [1]
valategrast Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition - - 2
⤷ [2]
zaurategrast Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition - - 7
⤷ [7]
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
BOP Peptide Click here for species-specific activity table Hs Antagonist 11.3 pKd 6
⤷ pKd 11.3 (Kd 5x10-12 M) [6]
Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Value Parameter Reference
natalizumab Peptide Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition - - 5
⤷ [5]
Antibody Comments
Approved antibody drug natalizumab has the integrin α4 subunit as its primary target.

References

Show »

1. Grove RA, Shackelford S, Sopper S, Pirruccello S, Horrigan J, Havrdova E, Gold M, Graff O. (2013) Leukocyte counts in cerebrospinal fluid and blood following firategrast treatment in subjects with relapsing forms of multiple sclerosis. Eur J Neurol, 20 (7): 1032-42. [PMID:23419064]

2. Hijazi Y, Welker H, Dorr AE, Tang JP, Blain R, Renzetti LM, Abbas R. (2004) Pharmacokinetics, safety, and tolerability of R411, a dual alpha4beta1-alpha4beta7 integrin antagonist after oral administration at single and multiple once-daily ascending doses in healthy volunteers. J Clin Pharmacol, 44 (12): 1368-78. [PMID:15545307]

3. Lin Kc, Ateeq HS, Hsiung SH, Chong LT, Zimmerman CN, Castro A, Lee WC, Hammond CE, Kalkunte S, Chen LL et al.. (1999) Selective, tight-binding inhibitors of integrin alpha4beta1 that inhibit allergic airway responses. J Med Chem, 42 (5): 920-34. [PMID:10072689]

4. Makino S, Okuzumi T, Yoshimura T, Satake Y, Suzuki N, Izawa H, Sagi K, Chiba A, Nakanishi E, Murata M et al.. (2011) New phenylalanine derivatives. Patent number: US20110065918A1. Assignee: EA Pharma Co Ltd. Priority date: 18/08/2000. Publication date: 17/03/2011.

5. No authors listed. (2004) Natalizumab: AN 100226, anti-4alpha integrin monoclonal antibody. Drugs R D, 5 (2): 102-7. [PMID:15293871]

6. Pepinsky RB, Mumford RA, Chen LL, Leone D, Amo SE, Riper GV, Whitty A, Dolinski B, Lobb RR, Dean DC et al.. (2002) Comparative assessment of the ligand and metal ion binding properties of integrins alpha9beta1 and alpha4beta1. Biochemistry, 41 (22): 7125-41. [PMID:12033947]

7. Wolf C, Sidhu J, Otoul C, Morris DL, Cnops J, Taubel J, Bennett B. (2013) Pharmacodynamic consequences of administration of VLA-4 antagonist CDP323 to multiple sclerosis subjects: a randomized, double-blind phase 1/2 study. PLoS One, 8 (3): e58438. [PMID:23472197]

How to cite this page