Discovery and evaluation of potent, cysteine-based alpha4beta1 integrin antagonists

S C Archibald; J C Head; J M Linsley; J R Porter; M K Robinson; A Shock; G J Warrellow

doi:10.1016/s0960-894x(00)00146-3

Discovery and evaluation of potent, cysteine-based alpha4beta1 integrin antagonists

Bioorg Med Chem Lett. 2000 May 1;10(9):993-5. doi: 10.1016/s0960-894x(00)00146-3.

Authors

S C Archibald¹, J C Head, J M Linsley, J R Porter, M K Robinson, A Shock, G J Warrellow

Affiliation

¹ Celltech Chiroscience, Slough, UK.

PMID: 10853676
DOI: 10.1016/s0960-894x(00)00146-3

Abstract

Acyclic, disulphide derivatives of cysteine have been identified as moderately potent antagonists of alpha4beta1-mediated leukocyte cell adhesion to VCAM. This communication describes how they were discovered from a simple L-cystine derivative and using the structure-activity data of C*DThioPC* related cyclic peptides.

MeSH terms

Cysteine / chemistry*
Cysteine / pharmacology
Integrin alpha4beta1
Integrins / antagonists & inhibitors*
Interleukin-8 / pharmacology
Protein Binding
Receptors, Lymphocyte Homing / antagonists & inhibitors*
Structure-Activity Relationship
Vascular Cell Adhesion Molecule-1 / metabolism

Substances

Integrin alpha4beta1
Integrins
Interleukin-8
Receptors, Lymphocyte Homing
Vascular Cell Adhesion Molecule-1
Cysteine