Future challenges facing the development of specific active-site-directed synthetic inhibitors of MMPs

Despite a deep knowledge on the 3D-structure of several catalytic domains of MMPs, the development of highly specific synthetic active-site-directed inhibitors of MMPs, able to differentiate the different members of this protease family, remains a strong challenge. Due to the flexible nature of NIMP active-site, the development of specific NIMP inhibitors will need to combine sophisticated theoretical and experimental approaches to decipher in each MMP the specific structural and dynamic features that can be exploited to obtain the desired selectivity. (c) 2004 Elsevier SAS. All rights reserved.