MSC2530818

上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白,专注于信号通路和疾病研究领域。

MSC2530818  纯度: 99.69%

MSC2530818是有效,选择性,有口服活性的 CDK8 抑制剂,抑制 CDK8 的IC50值为2.6 nM。

MSC2530818

MSC2530818 Chemical Structure

CAS No. : 1883423-59-3

规格 价格 是否有货 数量
10 mM * 1 mL in DMSO ¥1980 In-stock
5 mg ¥1800 In-stock
10 mg ¥3100 In-stock
25 mg ¥6600 In-stock
50 mg ¥11300 In-stock
100 mg 询价

* Please select Quantity before adding items.

MSC2530818 相关产品

相关化合物库:

  • Bioactive Compound Library Plus
  • Cell Cycle/DNA Damage Compound Library
  • Kinase Inhibitor Library
  • Anti-Cancer Compound Library
  • Anti-Aging Compound Library
  • Orally Active Compound Library
  • Anti-Breast Cancer Compound Library
  • Anti-Blood Cancer Compound Library
  • Targeted Diversity Library

生物活性

MSC2530818 is a potent, selective and orally available CDK8 inhibitor with an IC50 of 2.6 nM for CDK8.

IC50 & Target

CDK8

2.6 nM (IC50)

体外研究
(In Vitro)

MSC2530818 binds to CDK8 and CDK19 with similar affinity (4 nM). Potent inhibition of phospho-STAT1SER727, an established biomarker of CDK8 activity, in SW620 human colorectal carcinoma cells is also observed (pSTAT1SER727 IC50=8±2 nM). MSC2530818 demonstrates potent inhibition of WNT-dependent transcription in human cancer cell lines that have constitutively activated WNT signaling. For example, MSC2530818 inhibits the reporter-based luciferase readout in several cell lines bearing activating WNT-pathway mutations; LS174T (β-catenin mutant, IC50=32±7 nM), COLO205 (APC mutant, IC50=9±1 nM) and demonstrates inhibition of WNT3a ligand-dependent reporter readout in PA-1 cells (IC50=52±30 nM). MSC2530818 demonstrates minimal activity in the CEREP panel, and demonstrates minimal hERG inhibition. Furthermore, MSC2530818 is a soluble CDK8 inhibitor with high permeability and low efflux ratio in Caco-2 cells and does not inhibit any cytochrome P450 subtypes[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

体内研究
(In Vivo)

Tumor-bearing mice treated with MSC2530818 shows reduction in tumor growth with T/C ratios (based on final tumor weights) of 49% and 57%, respectively. MSC2530818 is generally well tolerated, with no effects on mouse body weight in the qd administration schedule and manageable body weight loss. The human clearance and volume of distribution at steady-state are estimated to be low (0.14 L/h/kg) and small (0.48 L/kg), respectively, resulting in a short predicted terminal half-life (2.4 h). Physiologically based pharmacokinetics simulations suggested that human oral bioavailability may be ≥75% up to dose level of 500 mg daily[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

分子量

340.81

Formula

C18H17ClN4O

CAS 号

1883423-59-3

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
溶解性数据
In Vitro: 

DMSO : 110 mg/mL (322.76 mM; Need ultrasonic)

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 2.9342 mL 14.6709 mL 29.3419 mL
5 mM 0.5868 mL 2.9342 mL 5.8684 mL
10 mM 0.2934 mL 1.4671 mL 2.9342 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°C, 6 months; -20°C, 1 month。-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。

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: ≥ 2.75 mg/mL (8.07 mM); Clear solution

    此方案可获得 ≥ 2.75 mg/mL (8.07 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 27.5 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中,混合均匀;向上述体系中加入50 μL Tween-80,混合均匀;然后继续加入 450 μL生理盐水定容至 1 mL。

    将 0.9 g 氯化钠,完全溶解于 100 mL ddH₂O 中,得到澄清透明的生理盐水溶液

  • 2.

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

    Solubility: 2.75 mg/mL (8.07 mM); Suspended solution; Need ultrasonic

    此方案可获得 2.75 mg/mL (8.07 mM) 的均匀悬浊液,悬浊液可用于口服和腹腔注射。

    以 1 mL 工作液为例,取 100 μL 27.5 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。

    将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中,再用生理盐水定容至 10 mL,完全溶解,澄清透明
  • 3.

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

    Solubility: ≥ 2.75 mg/mL (8.07 mM); Clear solution

    此方案可获得 ≥ 2.75 mg/mL (8.07 mM,饱和度未知) 的澄清溶液,此方案不适用于实验周期在半个月以上的实验。

    以 1 mL 工作液为例,取 100 μL 27.5 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中,混合均匀。

*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献
  • [1]. Czodrowski P, et al. Structure-Based Optimization of Potent, Selective, and Orally Bioavailable CDK8 Inhibitors Discovered by High-Throughput Screening. J Med Chem. 2016 Oct 27;59(20):9337-9349.

Animal Administration
[1]

Mice: MSC2530818 is then assessed in an established SW620 human colorectal cancer xenograft model in female NCr athymic mice. Tumor-bearing mice are treated orally with MSC2530818 (50 mg/kg bid or 100 mg/kg qd) for 16 days. Tumor weights are measured and body weights are monitored[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

参考文献
  • [1]. Czodrowski P, et al. Structure-Based Optimization of Potent, Selective, and Orally Bioavailable CDK8 Inhibitors Discovered by High-Throughput Screening. J Med Chem. 2016 Oct 27;59(20):9337-9349.

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