OTS964

製品コードS7648 バッチS764804

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₂₃H₂₄N₂O₂S.HCl

分子量

428.97

CAS No.

1338545-07-5

Solubility (25°C)*

体外

DMSO

22 mg/mL (51.28 mM)

Water

Insoluble

Ethanol

Insoluble

体内（毎回新しく調製した物を用意してください）

	5% DMSO 1 95% Corn oil	0.25mg/ml
	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O	1.1mg/ml

* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	OTS964 is a potent TOPK inhibitor with high affinity and selectivity and IC50 value is 28 nM. OTS964 is also a potent inhibitor of the cyclin-dependent kinase CDK11 with Kd of 40 nM. OTS964 treatment activates autophagy in glioma cells and induces apoptosis of human lung cancer cells in mouse xenografts.
in vitro	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 290nM. 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^[1].
in vivo	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^[1].

プロトコル(参考用のみ)

細胞アッセイ	細胞株	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
	濃度	--
	反応時間	72 h
	実験の流れ	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.
動物実験	動物モデル	BALB/cSLC-nu/nu mice
	投薬量	40 mg/kg
	投与方法	i.v.

参考

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

P-TEFb promotes cell survival upon p53 activation by suppressing intrinsic apoptosis pathway [ Nucleic Acids Res, 2023, gkad001]	PubMed: 36727434
Phosphorylation of PBK/TOPK Tyr74 by JAK2 promotes Burkitt lymphoma tumor growth [ Cancer Lett, 2022, 544:215812]	PubMed: 35780928
TOPK/PBK is phosphorylated by ERK2 at serine 32, promotes tumorigenesis and is involved in sorafenib resistance in RCC [ Cell Death Dis, 2022, 13(5):450]	PubMed: 35546143
SCFFBXW7 regulates G2-M progression through control of CCNL1 ubiquitination [ EMBO Rep, 2022, e55044]	PubMed: 36278408
[18F]FE-OTS964: a Small Molecule Targeting TOPK for In Vivo PET Imaging in a Glioblastoma Xenograft Model [ Mol Imaging Biol, 2019, 21(4):705-712]	PubMed: 30357568

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。