aDivision of Medicinal Chemistry, National Research Institute of Chinese Medicine bInstitute of Biophotonics, National Yang Ming University, Taipei cInstitute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Miaoli, Taiwan, Republic of China.
Anticancer Drugs. 2013 Nov;24(10):1047-57. doi: 10.1097/CAD.0000000000000014.
BPR0C305 is a novel N-substituted indolyl glyoxylamide previously reported with in-vitro cytotoxic activity against a panel of human cancer cells including P-gp-expressing multiple drug-resistant cell sublines. The present study further examined the underlying molecular mechanism of anticancer action and evaluated the in-vivo antitumor activities of BPR0C305. BPR0C305 is a novel synthetic small indole derivative that demonstrates in-vitro activities against human cancer cell growth by inhibiting tubulin polymerization, disrupting cellular microtubule assembly, and causing cell cycle arrest at the G2/M phase. It is also orally active against leukemia and solid tumor growths in mouse models. Findings of these pharmacological and pharmacokinetic studies suggest that BPR0C305 is a promising lead compound for further preclinical developments.
BPR0C305 是一种新型的 N-取代吲哚基乙二酰亚胺，先前已被报道具有体外细胞毒性活性，可抑制多种人癌细胞系，包括 P-糖蛋白表达的多药耐药细胞亚系。本研究进一步探讨了其抗癌作用的潜在分子机制，并评估了 BPR0C305 的体内抗肿瘤活性。BPR0C305 是一种新型的合成小吲哚衍生物，通过抑制微管蛋白聚合、破坏细胞微管组装和导致细胞周期停滞在 G2/M 期，显示出对人癌细胞生长的体外活性。它对白血病和实体肿瘤在小鼠模型中的生长也具有口服活性。这些药理学和药代动力学研究的结果表明，BPR0C305 是进一步临床前开发的有前途的先导化合物。
