The pipeline of new molecules and regimens against drug-resistant tuberculosis

The clinical development and regulatory approval of bedaquiline, delamanid and pretomanid over the last decade brought about significant progress in the management of drug-resistant tuberculosis, providing all-oral regimens with favorable safety profiles. The Nix-TB and ZeNix trials of a bedaquiline...

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Autores principales:	Todd A. Black, Ulrike K. Buchwald
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Drug-resistant tuberculosis Bedaquiline Delamanid Pretomanid Regimen development Animal models Diseases of the respiratory system RC705-779 Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/c279d47241634204875e2790a2ade4d4
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spelling	oai:doaj.org-article:c279d47241634204875e2790a2ade4d42021-11-14T04:34:27ZThe pipeline of new molecules and regimens against drug-resistant tuberculosis2405-579410.1016/j.jctube.2021.100285https://doaj.org/article/c279d47241634204875e2790a2ade4d42021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2405579421000747https://doaj.org/toc/2405-5794The clinical development and regulatory approval of bedaquiline, delamanid and pretomanid over the last decade brought about significant progress in the management of drug-resistant tuberculosis, providing all-oral regimens with favorable safety profiles. The Nix-TB and ZeNix trials of a bedaquiline – pretomanid – linezolid regimen demonstrated for the first time that certain forms of drug-resistant tuberculosis can be cured in the majority of patients within 6 months. Ongoing Phase 3 studies containing these drugs may further advance optimized regimen compositions. Investigational drugs in clinical development that target clinically validated mechanisms, such as second generation oxazolidinones (sutezolid, delpazolid, TBI-223) and diarylquinolines (TBAJ-876 and TBAJ-587) promise improved potency and/or safety compared to the first-in-class drugs. Compounds with novel targets involved in diverse bacterial functions such as cell wall synthesis (DrpE1, MmpL3), electron transport, DNA synthesis (GyrB), cholesterol metabolism and transcriptional regulation of ethionamide bioactivation pathways have advanced to early clinical studies with the potential to enhance antibacterial activity when added to new or established anti-TB drug regimens. Clinical validation of preclinical in vitro and animal model predictions of new anti-TB regimens may further improve the translational value of these models to identify optimal anti-TB therapies.Todd A. BlackUlrike K. BuchwaldElsevierarticleDrug-resistant tuberculosisBedaquilineDelamanidPretomanidRegimen developmentAnimal modelsDiseases of the respiratory systemRC705-779Infectious and parasitic diseasesRC109-216ENJournal of Clinical Tuberculosis and Other Mycobacterial Diseases, Vol 25, Iss , Pp 100285- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Drug-resistant tuberculosis Bedaquiline Delamanid Pretomanid Regimen development Animal models Diseases of the respiratory system RC705-779 Infectious and parasitic diseases RC109-216
spellingShingle	Drug-resistant tuberculosis Bedaquiline Delamanid Pretomanid Regimen development Animal models Diseases of the respiratory system RC705-779 Infectious and parasitic diseases RC109-216 Todd A. Black Ulrike K. Buchwald The pipeline of new molecules and regimens against drug-resistant tuberculosis
description	The clinical development and regulatory approval of bedaquiline, delamanid and pretomanid over the last decade brought about significant progress in the management of drug-resistant tuberculosis, providing all-oral regimens with favorable safety profiles. The Nix-TB and ZeNix trials of a bedaquiline – pretomanid – linezolid regimen demonstrated for the first time that certain forms of drug-resistant tuberculosis can be cured in the majority of patients within 6 months. Ongoing Phase 3 studies containing these drugs may further advance optimized regimen compositions. Investigational drugs in clinical development that target clinically validated mechanisms, such as second generation oxazolidinones (sutezolid, delpazolid, TBI-223) and diarylquinolines (TBAJ-876 and TBAJ-587) promise improved potency and/or safety compared to the first-in-class drugs. Compounds with novel targets involved in diverse bacterial functions such as cell wall synthesis (DrpE1, MmpL3), electron transport, DNA synthesis (GyrB), cholesterol metabolism and transcriptional regulation of ethionamide bioactivation pathways have advanced to early clinical studies with the potential to enhance antibacterial activity when added to new or established anti-TB drug regimens. Clinical validation of preclinical in vitro and animal model predictions of new anti-TB regimens may further improve the translational value of these models to identify optimal anti-TB therapies.
format	article
author	Todd A. Black Ulrike K. Buchwald
author_facet	Todd A. Black Ulrike K. Buchwald
author_sort	Todd A. Black
title	The pipeline of new molecules and regimens against drug-resistant tuberculosis
title_short	The pipeline of new molecules and regimens against drug-resistant tuberculosis
title_full	The pipeline of new molecules and regimens against drug-resistant tuberculosis
title_fullStr	The pipeline of new molecules and regimens against drug-resistant tuberculosis
title_full_unstemmed	The pipeline of new molecules and regimens against drug-resistant tuberculosis
title_sort	pipeline of new molecules and regimens against drug-resistant tuberculosis
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/c279d47241634204875e2790a2ade4d4
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The pipeline of new molecules and regimens against drug-resistant tuberculosis

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