Tasidotinhydrochloride是抗有丝分裂多肽Dolastatin15的肽类似物，作为微管组装和微管动力学的抑制剂。
CAS：623174-20-9
分子式：C32H59ClN6O5
分子量：643.3
纯度：98%
存储：Store at -20°C

Background:

Tasidotin hydrochloride is a peptide analog of the antimitotic depsipeptide dolastatin 15, as an inhibitor of microtubule assembly and microtubule dynamics.

Compared with other breast carcinoma lines, relatively low amounts of Tasidotin enters NCI/ADR-RES cells, consistent with Tasidotin’s also being a P-glycoprotein substrate. Of the remaining lines, the greatest difference in sensitivity to Tasidotin is between the more sensitive MDA-MB-435 line and the less sensitive HS 578-T line. The IC50 values in the two lines are 4 and 200 nM, respectively[1]. The IC50 in Ewing’s sarcoma, rhabdomyosarcoma, osteosarcoma, and synovial sarcoma lines ranges from 2 to 320 nM. In the SK-ES1 and RH30 cell lines, Tasidotin induces a G2-M arrest that persists for 48 h after Tasidotin is washed from the cells. In vitro, more than half the cells are in the early or late phase of apoptosis 48 h after treatment with Tasidotin. Following treatment for 24 h with 160 nM Tasidotin, the RH30 line and SK-ES1 line each shows an accumulation of cells in the G2-M phase. At hour 24, nearly all the RH30 cells are in the G2-M phase[2].

In vivo, a significant increase in apoptotic nuclei is apparent in xenograft tumors harvested within 24 h after a 5-day course of Tasidotin. Mice treated with 100 mg/kg have a mean weight loss of >20% with no return to their baseline starting weight, and one mouse dies before the second treatment course. The mice treated with 90 mg/kg/d Tasidotin have a mean weight loss of<16% following each 5-day treatment of Tasidotin[2].

[1]. Bai R, et al. Intracellular activation and deactivation of Tasidotin, an analog of dolastatin 15: correlation with cytotoxicity. Mol Pharmacol. 2009 Jan;75(1):218-26. [2]. Garg V, et al. Preclinical analysis of Tasidotin HCl in Ewing’s sarcoma, rhabdomyosarcoma, synovial sarcoma, and osteosarcoma. Clin Cancer Res. 2007 Sep 15;13(18 Pt 1):5446-54.