Novel inhibitors of alpha 4 beta 1 integrin receptor interactions through library synthesis and screening.
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.
Souers
A J
AJ
Department of Chemistry, University of California, Berkeley 94720, USA.
Virgilio
A A
AA
Schürer
S S
SS
Ellman
J A
JA
Kogan
T P
TP
West
H E
HE
Ankener
W
W
Vanderslice
P
P
D017398:Alternative Splicing; D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D019992:Databases as Topic; D015195:Drug Design; D039041:Integrin alpha4beta1; D016023:Integrins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics*; D008024:Ligands; D008968:Molecular Conformation; D015394:Molecular Structure; D016201:Receptors, Lymphocyte Homing / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics*; D016029:Receptors, Very Late Antigen / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics; D015203:Reproducibility of Results; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000596:Amino Acids; D002264:Carboxylic Acids; D039041:Integrin alpha4beta1; D016023:Integrins; D008024:Ligands; D016201:Receptors, Lymphocyte Homing; D016029:Receptors, Very Late Antigen