您好,欢迎来到化工原料网! [登录] [免费注册]
化工原料网
位置:首页 > 产品库 > Onatasertib
立即咨询
咨询类型:
     
*姓名:
*电话:
*单位:
Email:
*留言内容:
请详细说明您的需求。
*验证码:
 
Onatasertib
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Onatasertib图片
CAS NO:1228013-30-6
包装与价格:
包装价格(元)
10 mM * 1 mL in DMSO电议
2mg电议
5mg电议
10mg电议
50mg电议
100mg电议
200mg电议
500mg电议

产品名称
CC-223
ATG-008
产品介绍
Onatasertib (CC-223) 是一种口服有效的mTOR激酶抑制剂,抑制mTOR激酶,IC50为 16 nM。Onatasertib 抑制mTORC1mTORC2
生物活性

Onatasertib (CC-223) is a potent, selective, and orally bioavailable inhibitor ofmTORkinase, with anIC50value formTORkinase of 16 nM. Onatasertib inhibits bothmTORC1andmTORC2.

IC50& Target[1]

mTOR

16 nM (IC50)

mTORC1

 

mTORC2

 

DNA-PK

0.84 μM (IC50)

PI3K-α

4 μM (IC50)

体外研究
(In Vitro)

Onatasertib is a potent, selective, and orally bioavailable inhibitor of mTOR kinase, demonstrating inhibition of mTORC1 (pS6RP and p4EBP1) and mTORC2 [pAKT(S473)] in cellular systems. Onatasertib is selective for mTOR kinase with >200-fold selectivity over the related PI3K-α (IC50=4.0 μM). Of the PI3K related kinases tested, Onatasertib shows no significant inhibition of ATR or SMG1 and inhibits DNA-PK with an IC50value of 0.84 μM. When screened in a single-point assay against a commercially available panel of 246 kinases, only three kinases other than mTOR are inhibited >80% at 10 μM by Onatasertib. Upon follow-up IC50value determination, only two are inhibited by Onatasertib with IC50values below 1 μM; FLT4 (0.651 μM) and cFMS (0.028 μM). The exquisite kinase selectivity of Onatasertib is confirmed upon evaluation in cellular systems using ActivX KiNavtiv profiling. Other than mTOR kinase, no kinase target is identified when HCT 116 or A549 cells are treated for 1 hour with 1 μM Onatasertib and assayed for kinase activity. Onatasertib shows a concentration-dependent reduction in each marker, with IC50values of 31±2 nM for pS6RP, 405±47 nM for p4EBP1, and 11±10 nM for pAKT(S473) in western blot analysis. Inhibition of these pathway biomarkers is investigated in additional cell types from a variety of tissue origins. Onatasertib inhibits both mTORC1 (S6RP and 4EBP1) and mTORC2 [AKT(S473)] markers across the panel with IC50ranges of 27 to 184 nM for pS6RP, 120 to 1,050 nM for p4EBP1 and 11 to 150 nM for pAKT(S473)[1].

体内研究
(In Vivo)

The antitumor activity of Onatasertib in the PC-3 xenograft model is determined using a number of dosing paradigms. Onatasertib significantly inhibits PC-3 tumor growth in a dose- and schedule-dependent manner. Dosing at 10 or 25 mg/kg, once daily, results in 46% (P<0.001) and 87% (P<0.001) reduction in tumor volume, respectively. Similar dose dependency is observed with twice-daily dosing at 5 or 10 mg/kg, corresponding to 65% (P<0.001) and 80% (P<0.001) tumor volume reductions. All dose levels are tolerated in the once-daily and twice-daily dosing studies, with only the 25 mg/kg/d group showing any significant body weight loss. These mice lost approximately 10% of their initial body weight after 3 weeks of dosing[1].

Clinical Trial
分子量

397.47

性状

Solid

Formula

C21H27N5O3

CAS 号

1228013-30-6

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式
Powder-20°C3 years
4°C2 years
In solvent-80°C6 months
-20°C1 month
溶解性数据
In Vitro: 

DMSO : ≥ 27 mg/mL(67.93 mM)

*"≥" means soluble, but saturation unknown.

配制储备液
浓度溶剂体积质量1 mg5 mg10 mg
1 mM2.5159 mL12.5796 mL25.1591 mL
5 mM0.5032 mL2.5159 mL5.0318 mL
10 mM0.2516 mL1.2580 mL2.5159 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℃, 6 months; -20℃, 1 month。-80℃ 储存时,请在 6 个月内使用,-20℃ 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: ≥ 1.25 mg/mL (3.14 mM); Clear solution

    此方案可获得 ≥ 1.25 mg/mL (3.14 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 12.5 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-CDin saline)

    Solubility: ≥ 1.25 mg/mL (3.14 mM); Clear solution

    此方案可获得 ≥ 1.25 mg/mL (3.14 mM,饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例,取 100 μL 12.5 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 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
*以上所有助溶剂都可在本网站选购。