生物活性

• 描述Ixabepilone is an epothilone analogue that shows cytotoxic potency against tumor cell lines with IC₅₀ values ranging from 1.4 to 34.5 nM. The in vitro IC₉₀ values of ixabepilone in HCT116, HCT/VM46, A2780S, and A2780Tax cells were 7.3, 16, 6.9 and 12 nM, respectively. Ixabepilone potently induced tubulin polymerization with an EC_0.01 value of 3.5 μM. Eight-hour exposure of 7.5 nM ixabepilone almost completely blocked HCT116 cells in mitosis^[1]. Ixabepilone inhibited cell viability in triple negative breast cancer cell lines with the IC₅₀ values of 10 nM for MDA-MB-231 cells and 8 nM for SUM159 cells. After 72-hour incubation with 5 nM ixabepilone, the mammosphere formation in MDA-MB-231 and SUM159 cells were 0.21% and 0.30%, respectively. In immunocompromised nude rats implanted with Pat-7 tumor, i.v. administration of ixabepilone (3 mg/kg per injection) on a schedule of every 8 days × 2 elicited more than 5 log cell kill, and 4 of 6 cures. In A2780Tax human ovarian carcinoma xenograft, Iiabepilone (6.3 mg/kg per injection) on a schedule of every 2 days × 5 produced 2.5 log cell kill. In a paclitaxel-sensitive tumor model implanted with LS174T human colon carcinoma, ixabepilone (16 mg/kg per injection) administrated every 4 days × 3 yielded 2.3 log cell kill^[2].
• 作用机制The cellular cytotoxic activities of ixabepilone are linked to the induction of tubulin polymerization and the blockage of cell cycle progression in cancer cells^[1].

• 动物研究
  剂量	Mice: 3.2 mg/kg - 10 mg/kg[3] (i.v.), 18.8 mg/kg - 150 mg/kg[4] (i.v.), 48 mg/kg (p.o.) Rat: 8 mg/kg[4] (p.o.)
  给药途径	i.v., p.o.
  动物药代数据	Animal Mice[5] Dose 10 mg/kg Administration i.v. MRT 3.62 h AUCtot 5.77 μmol·h T1/2α 0.204 h T1/2β 9.23 h CL 57.8 ml/min/kg Cmax 14.7 μmol/L Vss 46.2 L/kg

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT00983801	Stomach Neoplasms	Phase 2	Completed	-	Hong Kong ... more >> Local Institution Hong Kong, Hong Kong, B Japan Local Institution Nagoya, Aichi, Japan, 4648681 Local Institution Sunto-Gun, Shizuoka, Japan, 4118777 Korea, Republic of Local Institution Seoul, Korea, Republic of, 135-710 Local Institution Seoul, Korea, Republic of, 136-705 Local Institution Seoul, Korea, Republic of, 138-736 Singapore Local Institution Singapore, Singapore, 169610 Taiwan Local Institution Taipei, Taiwan, 112 Local Institution Taoyuan Hsien, Taiwan, 333 Collapse <<
  NCT00077376	-	-	Completed	-	-
  NCT00017043	Esophageal Cancer ... more >> Gastric Cancer Collapse <<	Phase 2	Completed	-	United States, New York ... more >> Memorial Sloan-Kettering Cancer Center New York, New York, United States, 10021 Collapse <<

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• 参考文献

• [1] Lee FY, Borzilleri R, et al. BMS-247550: a novel epothilone analog with a mode of action similar to paclitaxel but possessing superior antitumor efficacy. Clin Cancer Res. 2001;7(5):1429-37.

  [2] Tanei T, Choi DS, et al. Antitumor activity of Cetuximab in combination with Ixabepilone on triple negative breast cancer stem cells. Breast Cancer Res. 2016;18(1):6.

  [3] Lee FY, Borzilleri R, et al. Preclinical discovery of ixabepilone, a highly active antineoplastic agent. Cancer Chemother Pharmacol. 2008 Dec;63(1):157-66.

  [4] BMS2475501

  [5] Peterson JK, Tucker C, et al. In vivo evaluation of ixabepilone (BMS247550), a novel epothilone B derivative, against pediatric cancer models. Clin Cancer Res. 2005 Oct 1;11(19 Pt 1):6950-8.

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