Changing the Rules of TB-Drug Discovery


The discovery of new drugs with novel targets is paramount to the continued success of tuberculosis (TB) treatment due to the increasing prevalence of antibiotic resistant infections in the TB population. Mycobacterium tuberculosis (Mtb) fumarate hydratase (fumarase) is a highly conserved essential protein that shares an active site with human fumarase, making active site inhibition equally cytotoxic for both bacteria and humans. The recent discovery of a set of new Mtb inhibitory compounds that target Mtb-fumarase by binding to a nonconserved allosteric site is a major advancement, providing further evidence to dispel the antibiotic discovery dogma that conserved proteins do not make good antibiotic targets.

Publication DOI:
Divisions: College of Health & Life Sciences > School of Biosciences
College of Health & Life Sciences
Additional Information: This document is the Accepted Manuscript version of a Published Work that appeared in final form in J. Med. Chem., copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see
Uncontrolled Keywords: Molecular Medicine,Drug Discovery
Publication ISSN: 1520-4804
Last Modified: 27 Jun 2024 10:14
Date Deposited: 04 Nov 2019 15:06
Full Text Link:
Related URLs: ... medchem.9b01716 (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2019-12-12
Published Online Date: 2019-10-30
Accepted Date: 2019-10-17
Authors: Harrison, James
Cox, Jonathan A. G. (ORCID Profile 0000-0001-5208-4056)



Version: Accepted Version

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