Changing the Rules of TB-Drug Discovery

James Harrison, Jonathan A. G. Cox

Research output: Contribution to journalArticle

Abstract

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.
Original languageEnglish
Pages (from-to)10583-10585
Number of pages3
JournalJournal of Medicinal Chemistry
Volume62
Issue number23
Early online date30 Oct 2019
DOIs
Publication statusPublished - 12 Dec 2019

Fingerprint

Fumarate Hydratase
Drug Discovery
Mycobacterium tuberculosis
Tuberculosis
Anti-Bacterial Agents
Catalytic Domain
Allosteric Site
Proteins
Bacteria
Infection
Population

Bibliographical note

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 https://doi.org/10.1021/acs.jmedchem.9b01716

Cite this

Harrison, James ; Cox, Jonathan A. G. / Changing the Rules of TB-Drug Discovery. In: Journal of Medicinal Chemistry. 2019 ; Vol. 62, No. 23. pp. 10583-10585.
@article{3c3ad981f11f425e837528cb28787192,
title = "Changing the Rules of TB-Drug Discovery",
abstract = "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.",
author = "James Harrison and Cox, {Jonathan A. G.}",
note = "This document is the Accepted Manuscript version of a Published Work that appeared in final form in J. Med. Chem., copyright {\circledC} American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.jmedchem.9b01716",
year = "2019",
month = "12",
day = "12",
doi = "10.1021/acs.jmedchem.9b01716",
language = "English",
volume = "62",
pages = "10583--10585",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "23",

}

Changing the Rules of TB-Drug Discovery. / Harrison, James; Cox, Jonathan A. G.

In: Journal of Medicinal Chemistry, Vol. 62, No. 23, 12.12.2019, p. 10583-10585.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Changing the Rules of TB-Drug Discovery

AU - Harrison, James

AU - Cox, Jonathan A. G.

N1 - 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 https://doi.org/10.1021/acs.jmedchem.9b01716

PY - 2019/12/12

Y1 - 2019/12/12

N2 - 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.

AB - 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.

UR - https://pubs.acs.org/doi/10.1021/acs.jmedchem.9b01716

UR - http://www.scopus.com/inward/record.url?scp=85074591084&partnerID=8YFLogxK

U2 - 10.1021/acs.jmedchem.9b01716

DO - 10.1021/acs.jmedchem.9b01716

M3 - Article

VL - 62

SP - 10583

EP - 10585

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 23

ER -