OTSSP167 (OTS167) hydrochlorid

OTSSP167 hydrochloride  (Synonyms: OTS167 hydrochloride)

OTSSP167 (OTS167) hydrochloride 是一种高效的，ATP 竞争性的 MELK 抑制剂，IC₅₀ 值为 0.41 nM。

美国medchemexpress（MCE)浙江省一级代理:杭州昊鑫生物科技股份有限公司
MCE中国是全球领先的科研化学品和生物活性化合物供应商，总部位于美国新泽西。我们的产品范围覆盖各种抑制剂、激动剂、API和化合物库。专业、高效的企业灵魂铸造了在行业的卓越地位。热情和充满活力的研发团队拥有着大量的化学和生物科学家。专注于生物活性化合物，拥有着多年的发展历程和丰富的行业经验。


生物活性    
OTSSP167 (OTS167) hydrochloride is a highly potent and ATP-competitive MELK inhibitor with IC50 value of 0.41 nM.

IC50 & Target    
IC50: 0.41 nM (MELK)

体外研究
(In Vitro)    
OTSSP167 inhibits the growth of A549 (lung), T47D (breast), DU4475 (breast), 22Rv1 (prostate) and HT1197 (bladder) cancer cells with IC50 values of 6.7, 4.3, 2.3, 6.0 and 97 nM, respectively[1].
OTSSP167 can abrogate the mitotic checkpoint, disrupt MCC and MCC-APC/C interaction in MCF7 cells. OTSSP167 causes GFP-MELK localization to cell cortex in prometaphase cells[2].
OTSSP167 is a MELK selective inhibitor, exhibits a strong in vitro activity, conferring an IC50 of 0.41 nM[3].

体内研究
(In Vivo)    
OTSSP167 (20 mg/kg, i.v.) results in tumor growth inhibition (TGI) of 73% in xenograft mouse model; OTSSP167 (1, 5, and 10 mg/kg, p.o.) reveals TGI of 51, 91, and 108%, respectively. OTSSP167 (20 mg/kg, p.o.) shows no tumor growth suppressive effect on PC-14 xenografts[1].

分子量    
523.88

性状    
Solid

Formula    
C25H29Cl3N4O2

CAS 号    
1431698-10-0

运输条件    
Room temperature in continental US; may vary elsewhere.

储存方式    
4°C, sealed storage, away from moisture

*In solvent : -80°C, 2 years; -20°C, 1 year (sealed storage, away from moisture)

溶解性数据    
In Vitro: 
DMSO : 33.33 mg/mL (63.62 mM; Need ultrasonic)

H2O : 7.14 mg/mL (13.63 mM; Need ultrasonic)

配制储备液    
浓度溶剂体积质量    1 mg    5 mg    10 mg
1 mM    1.9088 mL    9.5442 mL    19.0883 mL
5 mM    0.3818 mL    1.9088 mL    3.8177 mL
10 mM    0.1909 mL    0.9544 mL    1.9088 mL
*
请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 2 years; -20℃, 1 year (sealed storage, away from moisture)。-80℃ 储存时，请在 2 年内使用， -20℃ 储存时，请在 1 年 内使用。

In Vivo:
请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

1.
请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

Solubility: ≥ 3 mg/mL (5.73 mM); Clear solution

2.
请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

Solubility: ≥ 3 mg/mL (5.73 mM); Clear solution

3.
请依序添加每种溶剂： 10% DMSO    90% corn oil

Solubility: 3 mg/mL (5.73 mM); Suspended solution; Need ultrasonic

4.
请依序添加每种溶剂： PBS

Solubility: 1 mg/mL (1.91 mM); Clear solution; Need ultrasonic
 

参考文献

[1]. Chung S, Suzuki H, Miyamoto T, et al. Development of an orally-administrative MELK-targeting inhibitor that suppresses the growth of various types of human cancer. Oncotarget. 2012 Dec 21.  [Content Brief] [2]. Ji W, et al. OTSSP167 Abrogates Mitotic Checkpoint through Inhibiting Multiple Mitotic Kinases. PLoS One. 2016 Apr 15;11(4):e0153518.  [Content Brief] [3]. Cho YS, et al. The crystal structure of MPK38 in complex with OTSSP167, an orally administrative MELK selective inhibitor. Biochem Biophys Res Commun. 2014 Apr 25;447(1):7-11.  [Content Brief] [4]. Jurmeister S, et al. Identification of potential therapeutic targets in prostate cancer through a cross-species approach. EMBO Mol Med. 2018 Feb 5. pii: e8274.  [Content Brief] [5]. Meel MH, et al. MELK inhibition in Diffuse Intrinsic Pontine Glioma. Clin Cancer Res. 2018 Jul 30. pii: clincanres.0924.2018. [Content Brief]