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Last update 08 May 2025

QcrB

Last update 08 May 2025

Basic Info

Synonyms

Cytochrome bc1 complex cytochrome b subunit, Cytochrome bc1 reductase complex subunit QcrB, quinol--cytochrome-c reductase

+ [1]

Introduction-

Drugs associated with QcrB

TPN-0006290

Target

QcrB

Mechanism

QcrB inhibitors

Active Org.

Infectious Disease Research Institute

Originator Org.

Infectious Disease Research Institute

Active Indication

Mycobacterium Tuberculosis, Susceptibility to Infection By

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

TPN-0006267

Target

QcrB

Mechanism

QcrB inhibitors

Active Org.

Infectious Disease Research Institute

Originator Org.

Infectious Disease Research Institute

Active Indication

Mycobacterium Tuberculosis, Susceptibility to Infection By

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

TPN-0006245

Target

QcrB

Mechanism

QcrB inhibitors

Active Org.

Infectious Disease Research Institute

Originator Org.

Infectious Disease Research Institute

Active Indication

Mycobacterium Tuberculosis, Susceptibility to Infection By

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with QcrB

100 Translational Medicine associated with QcrB

0 Patents (Medical) associated with QcrB

Literatures (Medical) associated with QcrB

01 Dec 2025·Functional & Integrative Genomics

Comprehensive analysis of orthologous genes reveals functional dynamics and energy metabolism in the rhizospheric microbiome of Moringa oleifera

Article

Author: Baz, Lina ; Abuauf, Haneen W ; Barqawi, Aminah A ; Al-Andal, Abeer ; Almutrafy, Abeer M ; Jalal, Rewaa S ; Aloufi, Abeer S ; Alkhatib, Shaza N ; Sefrji, Fatmah O ; Abulfaraj, Aala A ; Tashkandi, Manal ; Alshareef, Sahar A ; Alnahari, Alaa A ; Alshehrei, Fatimah M

Moringa oleifera, known for its nutritional and therapeutic properties, exhibits a complex relationship with its rhizospheric soil microbiome. This study aimed to elucidate the microbiome's structural composition, molecular functions, and its role in plant growth by integrating Clusters of Orthologous Genes (COG) analysis with enzymatic functions previously identified through KEGG, CAZy, and CARD databases. Metagenomic sequencing and bioinformatics analysis were performed from the rhizospheric soil microbiome of M. oleifera collected from the Mecca district in Saudi Arabia. The analysis revealed a role for the rhizospheric microbiome in energy production, storage, and regulation, with glucose serving as a crucial precursor for NADH synthesis and subsequent ATP production via oxidative phosphorylation. Key orthologous genes (OGs) implicated in this process include NuoD, NuoH, NuoM, NuoN, NuoL, atpA, QcrB/PetB, and AccC. Additionally, OGs involved in ATP hydrolysis, such as ClpP, EntF, YopO, and AtoC, were identified. Taxonomic analysis highlighted Actinobacteria and Proteobacteria as the predominant phyla, with enriched genera including Blastococcus, Nocardioides, Streptomyces, Microvirga, Sphingomonas, and Massilia, correlating with specific OGs involved in ATP hydrolysis. This study provides insights into the molecular mechanisms underpinning plant-microbe interactions and highlights the multifaceted roles of ATP-dependent processes in the rhizosphere. Further research is recommended to explore the potential applications of these findings in sustainable agriculture and ecosystem management.

31 Jan 2025·Antimicrobial Agents and Chemotherapy

Contribution of telacebec to novel drug regimens in a murine tuberculosis model

Article

Author: Garcia, Andrew ; Nuermberger, Eric L. ; Converse, Paul J. ; Black, Todd ; Almeida, Deepak ; Fotouhi, Nader ; Li, Si-Yang ; Chang, Yong ; Tyagi, Sandeep ; Castillo, Jennie Ruelas ; Komm, Oliver D.

ABSTRACT The clinical efficacy of combination drug regimens containing the first-generation diarylquinoline (DARQ) bedaquiline in the treatment of multidrug-resistant tuberculosis has validated ATP synthesis as a vulnerable pathway in Mycobacterium tuberculosis . New DARQs in clinical development may be even more effective than bedaquiline, including against emerging bedaquiline-resistant strains. Telacebec (T) is a novel cytochrome bc 1 :aa 3 oxidase inhibitor that also inhibits ATP synthesis. Based on its demonstrated efficacy as a monotherapy in mice and in a phase 2a clinical trial, we tested the contribution of T to novel combination therapies against two strains of M. tuberculosis (H37Rv and HN878) in an established BALB/c mouse model of tuberculosis in an effort to find more effective regimens. Overall, T was more effective in regimens against the HN878 strain than against the H37Rv strain, a finding supported by the greater vulnerability of the former strain to T and to genetic depletion of QcrB. Against both strains, combinations of a DARQ, clofazimine, and T were highly bactericidal. However, only against HN878 did T contribute synergistically, whereas an antagonistic effect was observed against H37Rv. These results demonstrate the therapeutic potential of T and highlight how differences in the susceptibility of M. tuberculosis strains could lead to different conclusions about a drug’s potential contribution to novel drug regimens. CLINICAL TRIALS This study is registered with Clinicaltrials.gov

NCT04890535

and NCT06058299

11 Apr 2024·ACS Medicinal Chemistry Letters

Exploring Scaffold Hopping for Novel 2-(Quinolin-4-yloxy)acetamides with Enhanced Antimycobacterial Activity

Article

Author: da Silva Dadda, Adilio ; Silva Ramos, Alessandro ; Galina, Luiza ; Silveira Grams, Estevão ; de Matos Czeczot, Alexia ; Delgado Paz, Josiane ; Bizarro, Cristiano Valim ; Neves Muniz, Mauro ; Scheibler Rambo, Raoní ; Basso, Luiz Augusto ; Calle González, Laura ; Sperotto, Nathalia ; Silva Duarte, Lovaine ; Alberton Perelló, Marcia ; Abbadi, Bruno Lopes ; Machado, Pablo ; Fries da Silva, Fernanda ; Pissinate, Kenia ; Borsoi, Ana Flávia ; Souza Macchi Hopf, Fernanda

Utilizing a scaffold-hopping strategy from the drug candidate telacebec, a novel series of 2-(quinolin-4-yloxy)acetamides was synthesized and evaluated as inhibitors of Mycobacterium tuberculosis (Mtb) growth. These compounds demonstrated potent activity against drug-sensitive and multidrug-resistant strains (MIC ≤ 0.02 μM). Leading compounds were evaluated against a known qcrB resistant strain (T313A), and their loss in activity suggested that the cytochrome bc₁ complex is the likely target. Additionally, these structures showed high selectivity regarding mammalian cells (selectivity index > 500) and stability across different aqueous media. Furthermore, some of the synthesized quinolines demonstrated aqueous solubility values that exceeded those of telacebec, while maintaining low rates of metabolism. Finally, a selected compound prevented Mtb growth by more than 1.7 log₁₀ colony forming units in a macrophage model of tuberculosis (TB) infection. These findings validate the proposed design and introduce new 2-(quinolin-4-yloxy)acetamides with potential for development in TB drug discovery campaigns.

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QcrB

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