Novel inhibitors of alpha 4 beta 1 integrin receptor interactions through library synthesis and screening

Bioorg Med Chem Lett. 1998 Sep 8;8(17):2297-302. doi: 10.1016/s0960-894x(98)00416-8.

Abstract

A library of 2302 small molecule beta-turn mimetics was screened for inhibition of the alpha 4 beta 1 integrin-CS1 splice variant binding interaction. Preliminary data revealed several active ligands, and validation with purified material culminated in the identification of some of the first small molecule ligands (1, IC50 = 5 microM, and 2, IC50 = 8 microM) to be reported for this class of integrins.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alternative Splicing
  • Amino Acids / chemical synthesis*
  • Amino Acids / chemistry
  • Amino Acids / pharmacology
  • Binding Sites
  • Carboxylic Acids / chemical synthesis*
  • Carboxylic Acids / chemistry
  • Carboxylic Acids / pharmacology
  • Databases as Topic*
  • Drug Design
  • Integrin alpha4beta1
  • Integrins / antagonists & inhibitors*
  • Integrins / chemistry
  • Integrins / genetics*
  • Ligands
  • Molecular Conformation
  • Molecular Structure
  • Receptors, Lymphocyte Homing / antagonists & inhibitors*
  • Receptors, Lymphocyte Homing / chemistry
  • Receptors, Lymphocyte Homing / genetics*
  • Receptors, Very Late Antigen / antagonists & inhibitors
  • Receptors, Very Late Antigen / chemistry
  • Receptors, Very Late Antigen / genetics
  • Reproducibility of Results
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Amino Acids
  • Carboxylic Acids
  • Integrin alpha4beta1
  • Integrins
  • Ligands
  • Receptors, Lymphocyte Homing
  • Receptors, Very Late Antigen