Arylamide derivatives as allosteric inhibitors of the integrin alpha2beta1/type I collagen interaction.
We herein report a group of allosteric inhibitors of integrin alpha(2)beta(1) based on an arylamide scaffold. Compound 4 showed an IC(50) of 4.80 microM in disrupting integrin I-domain/collagen binding in an ELISA. These arylamide compounds are able to block collagen binding to integrin alpha(2)beta(1) on the platelet surface. Further we find that compound 4 recognizes a hydrophobic cleft on the side of the alpha(2) I-domain, suggesting an alternative targeting site for drug development.
Yin
Hang
H
Department of Biochemistry and Biophysics, University of Pennsylvania School of Medicine, Philadelphia, 19104, USA.
Gerlach
Lars Ole
LO
Miller
Meredith W
MW
Moore
David T
DT
Liu
Dahui
D
Vilaire
Gaston
G
Bennett
Joel S
JS
DeGrado
William F
WF