Mechanisms of Action of Novel Drugs Targeting Angiogenesis-Promoting Matrix Metalloproteinases.

ABSTRACT: Angiogenesis is facilitated by the proteolytic activities of members of the matrix metalloproteinase (MMP) family. More specifically, MMP-9 and MT1-MMP directly regulate angiogenesis, while several studies indicate a role for MMP-2 as well. The correlation of MMP activity to tumor angiogenesis has instigated numerous drug development programs. However, broad-based and Zn²⁺-chelating MMP inhibitors have fared poorly in the clinic. Selective MMP inhibition by antibodies, biologicals, and small molecules has utilized unique modes of action, such as (a) binding to protease secondary binding sites (exosites), (b) allosterically blocking the protease active site, or (c) preventing proMMP activation. Clinical trials have been undertaken with several of these inhibitors, while others ar

SUBMITTER: Fields GB 

PROVIDER: S-EPMC6558196 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature