KU-0063794, 雷帕霉素激酶机制靶点抑制剂

mTORC1 Selective Inhibitors

Moligand™

10mM in DMSO

CAS编号: 938440-64-3(DMSO)
分子式: C₂₅H₃₁N₅O₄
分子量: 465.54

有货

库存信息

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货号 (SKU)	包装规格	是否现货	价格	数量
K407923-1ml	1ml	现货

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Compound libraries (12332)

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基本描述

英文别名	(5-(2-((2R,6S)-2,6-dimethylmorpholino)-4-morpholinopyrido[2,3-d]pyrimidin-7-yl)-2-methoxyphenyl)methanol
规格或纯度	Moligand™, 10mM in DMSO
英文名称	KU-0063794
生化机理	KU-0063794 是一种强效、高度特异性的 mTOR 双抑制剂，在无细胞实验中对 mTORC1 和 mTORC2 的 IC50 值约为 10 nM；对 PI3Ks 无影响。
储存温度	-80℃储存
运输条件	超低温冰袋运输
作用类型	抑制剂
作用机制	雷帕霉素激酶机制靶点抑制剂
产品介绍	KU-0063794是mTORC1和mTORC2的选择性抑制剂，IC50为10 nM，对PI3Ks无抑制性。A FRAP (mTOR) inhibitor for both mTORC1 and mTORC2 Information KU-0063794 is a potent and highly specific dual-mTOR inhibitor ofmTORC1andmTORC2withIC50of ~10 nM in cell-free assays; no effect on PI3Ks. In vitro Compared with the mTOR inhibitor PP242, KU-0063794 exhibits higher specificity for mTOR, as being inactive against PI3Ks or 76 other kinases. In HEK-293 cells, KU-0063794 at 30 nM is sufficient to rapidly ablate S6K1 activity by blocking the phosphorylation of the hydrophobic motif (Thr³⁸⁹) and subsequently the phosphorylation of the T-loop residue (Thr²²⁹). In case of IGF1 stimulation of serum-starved HEK-293 cells, 300 nM of KU-0063794 is needed to inhibit the S6K1 activity by ~90%. KU-0063794 at 100-300 nM also completely inhibits the amino-acid-induced phosphorylation of S6K1 and S6 protein. Similar to S6K1, KU-0063794 inhibits the phosphorylation of mTORC1 at Ser²⁴⁴⁸ and mTORC2 at Ser²⁴⁸¹ in a dose-dependent and time-dependent manner. In the presence of serum or following IGF1 stimulation, KU-0063794 induces a dose-dependent inhibition of the activity and phosphorylation of Akt at Ser⁴⁷³ and unexpected Thr³⁰⁸ as well as the phosphorylation of the Akt substrates PRAS40 at Thr²⁴⁶, GSK3α/GSK3β at Ser²¹/Ser⁹ and Foxo-1/3a at Thr²⁴/Thr³². KU-0063794 but not rapamycin inhibits SGK1 activity and Ser⁴²² phosphorylation as well as its physiological substrate NDGR1 in a dose-dependent manner, to the same extent as S6K1 and Akt phosphorylation, whereas KU-0063794 dose not inhibit phorbol ester induced ERK or RSK phosphorylation and RSK activation. Compared with rapamycin, KU-0063794 exhibits more significant potency to induce the complete dephosphorylation of 4E-BP1 at Thr³⁷, Thr⁴⁶ and Ser⁶⁵. KU-0063794 inhibits cell growth of both wild-type and mLST8-deficient MEFs and induces a G1 cell cycle arrest, more significantly than rapamycin. In vivo Ku0063794 inhibits tumor growth and mTOR signaling in a preclinical renal cell carcinoma model. However, Ku0063794 was not more effective than temsirolimus in the animal study. A possible explanation for lack of greater activity in vivo for Ku0063794 is that temsirolimus has important effects on the tumor microenvironment. Temsirolimus decreased angiogenesis in the xenograft tumors while Ku0063794 did not. Temsirolimus treated tumors expressed less VEGF and PDGF than Ku0063794 treated tumors, thus stimulating less angiogenesis. Cell Data cell lines： Concentrations：Dissolved in DMSO, final concentration ~3 μM Incubation Time：24, 48, and 72 hours Powder Purity:≥95%

产品属性

IC50	mTORC1, IC50: ~10 nM
ALogP	3.274
hba_count	6
HBD Count	1
Rotatable Bond	5

关联靶点（人）

KCNH2 Tclin 钾电压门控通道亚家族 H 成员 2(Potassium voltage-gated channel subfamily H member 2) (1 活性数据)

点击查看靶蛋白信息： KCNH2

活性类型	活性值-log(M)	作用机制	期刊	参考文献(PubMed IDs)

MTOR Tclin 丝氨酸/苏氨酸蛋白激酶 mTOR(Serine/threonine-protein kinase mTOR) (4 活性数据)

点击查看靶蛋白信息： MTOR

活性类型	活性值-log(M)	作用机制	期刊	参考文献(PubMed IDs)

名称和识别符

分子类型	小分子
Canonical SMILES	COC1=C(CO)C=C(C=C1)C2=NC3=NC(=NC(=C3C=C2)N4CCOCC4)N5CC(C)OC(C)C5
分子量	465.54
Reaxy-Rn	26042203
Reaxys-RN link address	https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=26042203&ln=

化学和物理性质

溶解性	Solubility (25°C) In vitro DMSO: 57 mg/mL (201.17 mM); Ethanol: 19 mg/mL (67.05 mM); Water: Insoluble;
DMSO(mg / mL) Max Solubility	16
DMSO(mM) Max Solubility	34.37
Water(mg / mL) Max Solubility	<1