一种用于治疗BRCA缺陷型癌症的新型PARP抑制剂YHP-836
A Novel PARP Inhibitor YHP-836 For the Treatment of BRCA-Deficiency Cancers.
作者信息
Du Tingting, Zhang Zhihui, Zhou Jie, Sheng Li, Yao Haiping, Ji Ming, Xu Bailing, Chen Xiaoguang
机构信息
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
出版信息
Front Pharmacol. 2022 Jul 13;13:865085. doi: 10.3389/fphar.2022.865085. eCollection 2022.
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 . Oral administration of YHP-836 elicited remarkable antitumor activity either as a single agent or in combination with chemotherapy agents . These results indicated that YHP-836 is a well-defined PARP inhibitor.
PARP抑制剂在携带BRCA突变的患者中已在临床上显示出良好的抗肿瘤活性。在此，我们描述了一种新型PARP抑制剂YHP - 836，YHP - 836对PARP1和PARP2酶均表现出优异的抑制活性。它还通过DNA捕获对PARP1和PARP2进行变构调节。YHP - 836在携带BRCA突变的肿瘤细胞系中显示出细胞毒性，并诱导细胞周期停滞在G2/M期。YHP - 836还使肿瘤细胞对化疗药物敏感。口服YHP - 836作为单一药物或与化疗药物联合使用时均引发显著的抗肿瘤活性。这些结果表明YHP - 836是一种明确的PARP抑制剂。
Zotero 插件