Changing the Rules of TB-Drug Discovery

James Harrison; Jonathan A. G. Cox

doi:10.1021/acs.jmedchem.9b01716

Changing the Rules of TB-Drug Discovery

James Harrison
, Jonathan A. G. Cox

School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, U.K.

Research output: Contribution to journal › Article › peer-review

11 Citations (Scopus)

15 Downloads (Pure)

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 language	English
Pages (from-to)	10583-10585
Number of pages	3
Journal	Journal of Medicinal Chemistry
Volume	62
Issue number	23
Early online date	30 Oct 2019
DOIs	https://doi.org/10.1021/acs.jmedchem.9b01716
Publication status	Published - 12 Dec 2019

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Access to Document

10.1021/acs.jmedchem.9b01716

Changing the Rules of TB-Drug Discovery
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
Accepted author manuscript, 271 KB

Cite this

@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 {\textcopyright} 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 = dec,

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",

}

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 - https://www.scopus.com/pages/publications/85074591084

U2 - 10.1021/acs.jmedchem.9b01716

DO - 10.1021/acs.jmedchem.9b01716

M3 - Article

SN - 0022-2623

VL - 62

SP - 10583

EP - 10585

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 23

ER -

Changing the Rules of TB-Drug Discovery

Abstract

Bibliographical note

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this