title: 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.affiliation: 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.
authors.forename: Wen-Tai
authors.initials: WT
authors.lastname: Li
authors.forename: Teng-Kuang
authors.initials: TK
authors.lastname: Yeh
authors.forename: Jen-Shin
authors.initials: JS
authors.lastname: Song
authors.forename: Yung-Ning
authors.initials: YN
authors.lastname: Yang
authors.forename: Tung-Wei
authors.initials: TW
authors.lastname: Chen
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Lin
authors.forename: Ching-Ping
authors.initials: CP
authors.lastname: Chen
authors.forename: Chien-Chang
authors.initials: CC
authors.lastname: Shen
authors.forename: Chih-Chien
authors.initials: CC
authors.lastname: Hsieh
authors.forename: Heng-Liang
authors.initials: HL
authors.lastname: Lin
authors.forename: Yu-Sheng
authors.initials: YS
authors.lastname: Chao
authors.forename: Chiung-Tong
authors.initials: CT
authors.lastname: Chen
mesh_terms: D000284:Administration, Oral; D000634:Aminoquinolines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D007938:Leukemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008819:Mice, Nude; D008870:Microtubules / Q000187:drug effects* / Q000473:pathology; D014404:Tubulin / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000634:Aminoquinolines; D000970:Antineoplastic Agents; D007211:Indoles; C588148:N1-(6-quinolyl)-2-oxo-2-(1-(3-thienylmethyl)-1H-3-indolyl)acetamide; D014404:Tubulin