Last Updated: 19/06/2024

Development of malaria-selective covalent inhibitors targeting serine-metabolizing enzymes

Objectives

*Original title and abstract were machine translated from Japanese.

This study aims to elucidate the inhibition mechanism of malaria serine metabolizing enzyme (SHMT) selective inhibitor candidates obtained from drug search, and to develop into a covalent inhibitor that can inhibit Plasmodium in a physiological environment.

Principal Institution

University of Tokyo, Japan

Principal Investigators / Focal Persons

Masumi Shirakawa

Rationale and Abstract

Serine metabolizing enzyme (SHMT) is responsible for serine-glycine conversion, is involved in in vivo nucleic acid synthesis, and is an essential enzyme for the survival of Plasmodium malaria. Therefore, SHMT has been attracting attention in recent years as a new drug discovery target for Plasmodium malaria, whose drug resistance is becoming more serious every day. However, SHMTs are very similar between species and are also essential for maintaining normal human vital activity. Therefore, in the development of malaria SHMT inhibitors, it is an issue to have both “selectivity” and “medicinal efficacy” that inhibit only malaria SHMT.

External reference

Project details

Thematic Categories

Basic Science

Date

Apr 2022 — Mar 2025

Total Project Funding

$21,031

Funding Details

Japan Society for the Promotion of Science (JSPS), Japan

Grant ID: 22J21613

JPY 2.5M