Aspartic Proteases in Drug Discovery

Title: Aspartic Proteases in Drug Discovery

Volume: 13 Issue: 3

Author(s): Jorg Eder, Ulrich Hommel, Frederic Cumin, Bruno Martoglio and Bernd Gerhartz

Affiliation:

Keywords: Protease, Aspartic protease, inhibitor, BACE, HIV-protease, Renin, Presenilin

Abstract: Aspartic proteases are the smallest class of human proteases with only 15 members. Over the past years, they have received considerable attention as potential targets for pharmaceutical intervention since many have been shown to play important roles in physiological and pathological processes. Despite numerous efforts, however, the only inhibitors for aspartic proteases currently on the market are directed against the HIV protease, an aspartic protease of viral origin. Nevertheless, several inhibitors including those targeting renin, BACE1 and γ-secretase are in clinical or preclinical development, and some other aspartic proteases are discussed as potential drug target. The crystal structures of seven human aspartic proteases have now been solved and, together with a detailed kinetic understanding of their catalytic mechanism, this has greatly contributed to the design and discovery of novel inhibitors for this protease class. This review describes current aspartic protease drug targets and summarizes the drug discovery efforts in this field. In addition, it highlights recent developments which may lead to a new generation of aspartic protease inhibitors.

Cite this article as:

Eder Jorg, Hommel Ulrich, Cumin Frederic, Martoglio Bruno and Gerhartz Bernd, Aspartic Proteases in Drug Discovery, Current Pharmaceutical Design 2007; 13 (3) . https://dx.doi.org/10.2174/138161207779313560