BPR0C305, an orally active microtubule-disrupting anticancer agent.

Abstract

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.

• Authors: Wen-Tai Li, Teng-Kuang Yeh, Jen-Shin Song, Yung-Ning Yang, Tung-Wei Chen, Chi-Hung Lin, Ching-Ping Chen, Chien-Chang Shen, Chih-Chien Hsieh, Heng-Liang Lin, Yu-Sheng Chao, Chiung-Tong Chen
• Journal: Anti-cancer drugs (Anticancer Drugs) Vol. 24 Issue 10 Pg. 1047-57 (Nov 2013) ISSN: 1473-5741 [Electronic] England
• PMID: 24025560 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aminoquinolines
• Antineoplastic Agents
• Indoles
• N1-(6-quinolyl)-2-oxo-2-(1-(3-thienylmethyl)-1H-3-indolyl)acetamide
• Tubulin

Topics

• Administration, Oral
• Aminoquinolines (administration & dosage, pharmacokinetics, pharmacology, therapeutic use)
• Animals
• Antineoplastic Agents (administration & dosage, pharmacokinetics, pharmacology, therapeutic use)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Female
• Humans
• Indoles (administration & dosage, pharmacokinetics, pharmacology, therapeutic use)
• Leukemia (drug therapy, metabolism, pathology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred DBA
• Mice, Nude
• Microtubules (drug effects, pathology)
• Tubulin (metabolism)
• Xenograft Model Antitumor Assays