Author/Authors :
Linda L. Chang، نويسنده , , Quang Truong، نويسنده , , Richard A. Mumford، نويسنده , , Linda A. Egger، نويسنده , , Usha Kidambi، نويسنده , , Kathryn Lyons، نويسنده , , Ermengilda McCauley، نويسنده , , Gail Van Riper، نويسنده , , Stella Vincent، نويسنده , , John A. Schmidt، نويسنده , , Malcolm MacCoss، نويسنده , , William K. Hagmann، نويسنده ,
Abstract :
The α4β1 and α4β7 integrins are implicated in several inflammatory disease states. Systematic SAR studies of an α4β1-specific arylsulfonyl-Pro-Tyr lead led to the identification of a new α4β7 binding site, best captured by O-carbamates of Tyr for this structural class. Several compounds showed a 200- to 400-fold improvement in α4β7 binding affinity while maintaining subnanomolar α4β1 activity, for example 2l, VCAM-Ig α4β1 IC50=0.13 nM, VCAM-Ig α4β7 IC50=1.92 nM.
