Memapsin 2 (Beta-Secretase) Inhibitors: Drug Development

Title: Memapsin 2 (Beta-Secretase) Inhibitors: Drug Development

Volume: 5 Issue: 2

Author(s): Arun K. Ghosh, Nagaswamy Kumaragurubaran, Ling Hong, Gerald Koelsh and Jordan Tang

Affiliation:

Abstract: Memapsin 2 (β-secretase, BACE 1) processing of β-amyloid precursor protein is the first step in the pathway leading to the production of amyloid-β, thus, it is a major target for the development of inhibitor drug for the treatment of Alzheimerss Disease. Although there are distinctive advantages of this protease as a drug target, the development of drug-like memapsin 2 inhibitors has been somewhat slow since the cloning of the protease seven years ago. Here we review the progress of memapsin 2 inhibitor development using crystal structure-based design cycles. Recent progress has evolved the inhibitors into sizes sufficiently small to penetrate cell membranes and the blood-brain barrier yet retain potency for the inhibition of Aβ production in cultured cells and experimental animals. Such progress lends optimism that clinically useful memapsin 2 inhibitors will eventually be developed.

Cite this article as:

Ghosh K. Arun, Kumaragurubaran Nagaswamy, Hong Ling, Koelsh Gerald and Tang Jordan, Memapsin 2 (Beta-Secretase) Inhibitors: Drug Development, Current Alzheimer Research 2008; 5 (2) . https://dx.doi.org/10.2174/156720508783954730