Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.6.3.14 (
ATP synthase
)
7,042
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Introduction
: Tuberculosis (TB) is a leading infectious disease worldwide whose chemotherapy is challenged by the continued rise of drug resistance. This epidemic urges the need to discover anti-TB drugs with novel modes of action.
Areas covered
: The mycobacterial electron transport chain (ETC) pathway represents a hub of anti-TB drug targets. Herein, the authors highlight the various targets within the mycobacterial ETC and highlight some of the promising ETC-targeted drugs and clinical candidates that have been discovered or repurposed. Furthermore, recent breakthroughs in the availability of X-ray and/or cryo-EM structures of some targets are discussed, and various opportunities of exploiting these structures for the discovery of new anti-TB drugs are emphasized.
Expert opinion
: The drug discovery efforts targeting the ETC pathway have led to the FDA approval of bedaquiline, a F
O
F
1
-
ATP synthase
inhibitor, and the discovery of Q203, a clinical candidate drug targeting the mycobacterial cytochrome
bcc-aa3
supercomplex. Moreover, clofazimine, a proposed prodrug competing with menaquinone for its reduction by mycobacterial
NADH dehydrogenase 2
, has been repurposed for TB treatment. Recently available structures of the mycobacterial
ATP synthase
C9 rotary ring and the cytochrome
bcc-aa3
supercomplex represent further opportunities for the structure-based drug design (SBDD) of the next-generation of inhibitors against
Mycobacterium tuberculosis
.
...
PMID:Emerging opportunities of exploiting mycobacterial electron transport chain pathway for drug-resistant tuberculosis drug discovery. 3187 25
