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OTS964 HCl

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Chemical Structure| 1338545-07-5 同义名 : OTS-964;OTS964 (hydrochloride);OTS964 hydrochloride
CAS号 : 1338545-07-5
货号 : A217615
分子式 : C23H25ClN2O2S
纯度 : 99%+
分子量 : 428.975
MDL号 : MFCD28386220
存储条件：

粉末 Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 85 mg/mL(198.15 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

H2O: 2 mg/mL(4.66 mM)，配合低频超声，并水浴加热至45℃助溶
动物实验配方：
生物活性
靶点

  • TOPK

    TOPK, IC50:28 nM
描述 TOPK (T-lymphokine-activated killer cell-originated protein kinase) is highly and frequently transactivated in various cancer tissues, including lung and triple-negative breast cancers, and plays an indispensable role in the mitosis of cancer cells. OTS-964 is a potent TOPK inhibitor with high affinity and selectivity for TOPK kinase with IC50 value of 28 nM. OTS964 (2 μM) could inhibit 79.7% of TOPK activity, whereas the mean and the SD of the inhibitory effects against other kinases were 18.5 and 24.6%, respectively. OTS964 inhibited the growth of TOPK-positive cells with low IC50 values [A549 (31 nM), LU-99 (7.6 nM), DU4475 (53 nM), MDA-MB-231 (73 nM), T47D (72 nM), Daudi (25 nM), UM-UC-3 (32 nM), HCT-116 (33 nM), MKN1 (38 nM), MKN45 (39 nM), HepG2 (19 nM), MIAPaca-2 (30 nM), and 22Rv1 (50 nM)]. In mice bearing LU-99 lung cancer cells, a TGI (tumor growth inhibition) of 44% was observed on day 22 without any body weight loss after intravenous treatment of OTS964 at 40 mg/kg. A TGI of 110% was observed on day 22 after treatment of liposomal OTS964 at 40 mg/kg. The U-99 xenograft mice were intravenously treated with liposomal OTS964 (40 mg/kg) or vehicle at days 1, 4, 8, and 11, and tumors were collected on day 12. Treatment with OTS964 significantly increased the number of LU-99 cells with the “intercellular bridge” (P < 0.0001), which is one of the markers indicating impaired cell division. The oral administration of free OTS964 at 50 or 100 mg/kg once every day for 2 weeks resulted in TGIs of 79 and 113% on day 15, respectively, without any body weight loss in LU-99 xenograft model[2].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.33mL

0.47mL

0.23mL

11.66mL

2.33mL

1.17mL

23.31mL

4.66mL

2.33mL
参考文献

[1]Ikeda Y, Park JH, et al. T-LAK Cell-Originated Protein Kinase (TOPK) as a Prognostic Factor and a Potential Therapeutic Target in Ovarian Cancer. Clin Cancer Res. 2016 Dec 15;22(24):6110-6117.

[2] Matsuo Y, Park JH, Miyamoto T, et al. TOPK inhibitor induces complete tumor regression in xenograft models of human cancer through inhibition of cytokinesis. Sci Transl Med. 2014;6(259):259ra145.