化合物OTS964 T4135

Product Introduction
Bioactivity


英文名: OTS964 hydrochloride

描述: OTS964 hydrochloride (OTS964) 是一种口服有效的，高亲和力和选择性的 TOPK 抑制剂，IC50为 28 nM。它也是一种细胞周期蛋白依赖激酶 CDK11抑制剂，结合 CDK11B 的 Kd 值为 40 nM。

细胞实验: Cell lines:?A549 cells, LU-99 cells, DU4475 cells, MDA-MB-231 cells, T47D cells, Daudi cells, UM-UC-3 cells, HCT-116 cells, MKN1 cells, MKN45 cells, HepG2 cells, MIAPaca-2 cells, 22Rv1 cells and HT29 cells Concentrations: --Incubation Time: 72 h Method: Cells (100 μl) are plated in 96-well plates at a certain density. The cells are allowed to adhere overnight before exposure to compounds for 72 hours at 37°C. Plates are read with a spectrophotometer at a wavelength of 450 nm. All assays are carried out in triplicate. After measuring IC50 values, we calculates the z scores to produce P values. After log transformation (base 10) of IC50 values (nM), the mean and SD are calculated for the log values of the IC50 for the 13 TOPK-positive cell lines.Method: Cells (100 μl) are plated in 96-well plates at a certain density. The cells are allowed to adhere overnight before exposure to compounds for 72 hours at 37°C. Plates are read with a spectrophotometer at a wavelength of 450 nm. All assays are carried out in triplicate. After measuring IC50 values, we calculates the z scores to produce P values. After log transformation (base 10) of IC50 values (nM), the mean and SD are calculated for the log values of the IC50 for the 13 TOPK-positive cell lines.

动物实验: Animal Models: BALB/cSLC-nu/nu miceFormulation: 5% glucoseDosages: 40 mg/kgAdministration: i.v.

体外活性: OTS964 inhibits the growth of TOPK-positive cells with low IC50 values [A549 (31 nM), LU-99 (7.6 nM), DU4475 (53 nM), MDAMB- 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)], whereas its growth inhibitory effect against TOPK-negative HT29 cancer cells is significantly weaker, with IC50 of 290 nM. Although OTS964 reveals some suppressive effect on Src family kinases, the response to OTS964 in these cancer cells is not correlated with the expression of Src family kinases c-Src, Fyn, and Lyn, supporting the TOPK-dependent growth inhibitory effects of OTS964. Time lapse imaging in T47D cells shows that treatment with OTS964 induces cytokinesis defects followed by apoptosis

体内活性: Although administration of the free compound induces hematopoietic adverse reactions (leukocytopenia associated with thrombocytosis), the drug delivered in a liposomal formulation effectively causes complete regression of transplanted tumors without showing any adverse reactions in mice. Inhibition of TOPK activity with the liposomal OTS964 suppresses tumor growth through induction of cytokinesis defects and subsequent apoptosis. Although oral administration of OTS964 causes some hematopoietic toxicity, this is a transient effect. The spontaneous recovery from leukocytopenia is occured and the anticancer effectiveness of the oral drug is similar to that of the liposomal formulation, oral administration of the drug may prove to be more practical

存储条件: Powder: -20°C for 3 years | In solvent: -80°C for 1 year

溶解度: Ethanol : 1 mg/mL (2.33 mM)
DMSO : 79 mg/mL (184.2 mM)
H2O : < 1 mg/mL (insoluble or slightly soluble)


关键字: OTS964 hydrochloride | inhibit | Inhibitor | Apoptosis | TOPK | Cyclin dependent kinase | OTS-964 Hydrochloride | CDK | OTS 964 | OTS-964 hydrochloride | OTS964 Hydrochloride | OTS-964 | OTS 964 Hydrochloride

相关产品: Hexamethonium Bromide | Antitumor agent-92 | Decitabine | Talampanel | α-Thujone | Pyrogallol | Bullatine A | CDKI-73 | Diclofenac | SP2509

相关库: Anti-Prostate Cancer Compound Library | Anti-Liver Cancer Compound Library | Cell Cycle Compound Library | Bioactive Compounds Library Max | Kinase Inhibitor Library | Inhibitor Library | Anti-Cancer Active Compound Library | Apoptosis Compound Library | Autophagy Compound Library | Anti-Pancreatic Cancer Compound Library

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