A Novel PARP Inhibitor YHP-836 For the Treatment of BRCA-Deficiency Cancers

PARP inhibitors have clinically demonstrated good antitumor activity in patients with BRCA mutations. Here, we described YHP-836, a novel PARP inhibitor, YHP-836 demonstrated excellent inhibitory activity for both PARP1 and PARP2 enzymes. It also allosterically regulated PARP1 and PARP2 via DNA trap...

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Detalles Bibliográficos
Autores principales: Du, Tingting, Zhang, Zhihui, Zhou, Jie, Sheng, Li, Yao, Haiping, Ji, Ming, Xu, Bailing, Chen, Xiaoguang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Pharmacology
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326368/
https://www.ncbi.nlm.nih.gov/pubmed/35910366
http://dx.doi.org/10.3389/fphar.2022.865085
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author Du, Tingting
Zhang, Zhihui
Zhou, Jie
Sheng, Li
Yao, Haiping
Ji, Ming
Xu, Bailing
Chen, Xiaoguang
author_facet Du, Tingting
Zhang, Zhihui
Zhou, Jie
Sheng, Li
Yao, Haiping
Ji, Ming
Xu, Bailing
Chen, Xiaoguang
author_sort Du, Tingting
collection PubMed
description PARP inhibitors have clinically demonstrated good antitumor activity in patients with BRCA mutations. Here, we described YHP-836, a novel PARP inhibitor, YHP-836 demonstrated excellent inhibitory activity for both PARP1 and PARP2 enzymes. It also allosterically regulated PARP1 and PARP2 via DNA trapping. YHP-836 showed cytotoxicity in tumor cell lines with BRCA mutations and induced cell cycle arrest in the G2/M phase. YHP-836 also sensitized tumor cells to chemotherapy agents in vitro. Oral administration of YHP-836 elicited remarkable antitumor activity either as a single agent or in combination with chemotherapy agents in vivo. These results indicated that YHP-836 is a well-defined PARP inhibitor.
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spelling pubmed-93263682022-07-28 A Novel PARP Inhibitor YHP-836 For the Treatment of BRCA-Deficiency Cancers Du, Tingting Zhang, Zhihui Zhou, Jie Sheng, Li Yao, Haiping Ji, Ming Xu, Bailing Chen, Xiaoguang Front Pharmacol Pharmacology PARP inhibitors have clinically demonstrated good antitumor activity in patients with BRCA mutations. Here, we described YHP-836, a novel PARP inhibitor, YHP-836 demonstrated excellent inhibitory activity for both PARP1 and PARP2 enzymes. It also allosterically regulated PARP1 and PARP2 via DNA trapping. YHP-836 showed cytotoxicity in tumor cell lines with BRCA mutations and induced cell cycle arrest in the G2/M phase. YHP-836 also sensitized tumor cells to chemotherapy agents in vitro. Oral administration of YHP-836 elicited remarkable antitumor activity either as a single agent or in combination with chemotherapy agents in vivo. These results indicated that YHP-836 is a well-defined PARP inhibitor. Frontiers Media S.A. 2022-07-13 /pmc/articles/PMC9326368/ /pubmed/35910366 http://dx.doi.org/10.3389/fphar.2022.865085 Text en Copyright © 2022 Du, Zhang, Zhou, Sheng, Yao, Ji, Xu and Chen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Du, Tingting
Zhang, Zhihui
Zhou, Jie
Sheng, Li
Yao, Haiping
Ji, Ming
Xu, Bailing
Chen, Xiaoguang
A Novel PARP Inhibitor YHP-836 For the Treatment of BRCA-Deficiency Cancers
title A Novel PARP Inhibitor YHP-836 For the Treatment of BRCA-Deficiency Cancers
title_full A Novel PARP Inhibitor YHP-836 For the Treatment of BRCA-Deficiency Cancers
title_fullStr A Novel PARP Inhibitor YHP-836 For the Treatment of BRCA-Deficiency Cancers
title_full_unstemmed A Novel PARP Inhibitor YHP-836 For the Treatment of BRCA-Deficiency Cancers
title_short A Novel PARP Inhibitor YHP-836 For the Treatment of BRCA-Deficiency Cancers
title_sort novel parp inhibitor yhp-836 for the treatment of brca-deficiency cancers
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326368/
https://www.ncbi.nlm.nih.gov/pubmed/35910366
http://dx.doi.org/10.3389/fphar.2022.865085
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