Discovery of a new class of protein farnesyltransferase inhibitors in the arylthiophene series.

Sébastien Lethu (1) , Maryon Ginisty (1) , Damien Bosc (1) , Joëlle Dubois (1)

1 ICSN - Institut de Chimie des Substances Naturelles

Screening of the ICSN chemical library led to the discovery of 3-(4-chlorophenyl)-4-cyano-5-thioalkylthiophene 2-carboxylic acids as potent farnesyltransferase inhibitors. Enzymatic kinetic studies showed that this original FTI series belongs to the CaaX competitive inhibitor class. Preliminary SAR studies allowed us to improve the IC(50) from 110 to 7.5 nM.

Domaines: Biologie cellulaire

Sébastien Lethu, Maryon Ginisty, Damien Bosc, Joëlle Dubois. Discovery of a new class of protein farnesyltransferase inhibitors in the arylthiophene series.. Journal of Medicinal Chemistry, 2009, 52 (20), pp.6205-8. ⟨10.1021/jm901280q⟩. ⟨hal-00424981⟩