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Izorlisib
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。
Izorlisib图片
CAS NO:1007207-67-1
包装与价格:
包装价格(元)
10 mM * 1 mL in DMSO电议
5mg电议
10mg电议
50mg电议
100mg电议
200mg电议
500mg电议

产品名称
CH5132799
产品介绍
Izorlisib (CH5132799) 是一种选择性的 I 类PI3K抑制剂。抑制 PI3Kα,IC50为 14 nM。
生物活性

Izorlisib (CH5132799) is a selective class IPI3Kinhibitor. Izorlisib inhibits class I PI3Ks, particularlyPI3Kα, with anIC50of 14 nM.

IC50& Target[1]

PI3Kα

14 nM (IC50)

PI3Kα-H1047R

5.6 nM (IC50)

PI3Kα-E545K

6.7 nM (IC50)

PI3Kα-E542K

6.7 nM (IC50)

PI3Kγ

36 nM (IC50)

PI3Kβ

120 nM (IC50)

PI3Kδ

500 nM (IC50)

PI3KC2β

5.3 μM (IC50)

mTOR

1.6 μM (IC50)

体外研究
(In Vitro)

Izorlisib (CH5132799) is a selective class I PI3K inhibitor with potent antitumor activity against tumors harboring the PIK3CA mutations. Izorlisib selectively inhibits class I PI3Ks and PI3Kα mutants in in vitro kinase assays. Izorlisib inhibits class I PI3Ks, particularly PI3Kα, with an IC50of 14 nM. IC50values against class II PI3Ks (C2α and C2β), a class III PI3K (Vps34), and a class IV PI3K (mTOR) are more than 100-fold higher than that against PI3Kα. Interestingly, slightly lower IC50values are observed against PI3Kα with oncogenic mutations E542K, E545K, and H1047R than against wild-type (WT) PI3Kα. In an analysis of cocrystal structure with PI3Kγ (PBD ID: 3APC), Izorlisib is shown to interact with ATP-binding sites of the enzyme, suggesting an ATP competitive mode of inhibition. No significant inhibitory activities of Izorlisib are observed against a representative panel of 26 protein kinases, including RTKs, nonreceptor tyrosine kinases, and serine/threonine kinases. These data indicate that Izorlisib is a selective class I PI3K inhibitor, especially against PI3Kα and its mutants. Izorlisib shows superior antiproliferative activity across the 4 tumor types, with 75% (45/60) of lines having an IC50below 1 μM and 38% (23/60) of lines having an IC50below 0.3 μM[1].

体内研究
(In Vivo)

Mice bearing BT-474 tumors (n=14) are orally administered 50 mg/kg of Everolimus on a daily basis for 31 days and then randomized. After randomization, the mice are orally administered 50 mg/kg of Everolimus (n=4) and 12.5 mg/kg (n=5), and 25 mg/kg (n=5) of Izorlisib on a daily basis for 7 days. C, the vehicle-, Everolimus, and CH5132799-treated (25 mg/kg) tumors are resected at 4 hours after terminal administration in B, lysed, and analyzed by Western blotting. Izorlisib administration leads to a remarkable regression in a dose-dependent manner of the tumors regrown after the long-term Everolimus treatment. The tumors are resected at the end of treatment and analyzed by Western blotting with respect to PI3K pathway inhibition. Izorlisib suppresses various effectors in the PI3K pathway, including Akt, FoxO1, S6K, S6, and 4E-BP1, whereas Everolimus inhibits only phosphorylation of S6K and S6, both downstream effectors of mTORC1[1].

Clinical Trial
分子量

377.42

性状

Solid

Formula

C15H19N7O3S

CAS 号

1007207-67-1

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 : 4.55 mg/mL(12.06 mM;Need ultrasonic)

配制储备液
浓度溶剂体积质量1 mg5 mg10 mg
1 mM2.6496 mL13.2478 mL26.4957 mL
5 mM0.5299 mL2.6496 mL5.2991 mL
10 mM0.2650 mL1.3248 mL2.6496 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    90%corn oil

    Solubility: ≥ 0.46 mg/mL (1.22 mM); Clear solution

    此方案可获得 ≥ 0.46 mg/mL (1.22 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 4.6 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本网站选购。