Vevorisertib trihydrochloride ARQ 751 trihydrochloride|cas:1416775-08-0|西域试剂

Vevorisertib trihydrochloride ARQ 751 trihydrochloride,99.13%

产品编号：Bellancom-137458A| CAS NO：1416775-08-0| 分子式：C₃₅H₄₁Cl₃N₈O| 分子量：696.11

本网站销售的所有产品仅用于工业应用或者科学研究等非医疗目的,不可用于人类或动物的临床诊断或者治疗,非药用,非食用，

货号	包装	价格	库存与货期	购买量	操作
Bellancom-137458A		￥5500.00	杭州北京（现货）
Bellancom-137458A		￥9000.00	杭州北京（现货）

增值税发票√顺丰快递√订货电话：18601927057

Vevorisertib trihydrochloride ARQ 751 trihydrochloride

产品介绍

Vevorisertib (ARQ 751) trihydrochloride 是选择性、变构、pan-AKT 和 AKT1-E17K 突变抑制剂，可有效抑制 AKT 的磷酸化。Vevorisertib trihydrochloride 对 AKT1 和 AKT1-E17K 的 Kd 值分别为 1.2 nM 和 8.6 nM。Vevorisertib trihydrochloride 对 AKT1、AKT2 和 AKT3 的 IC₅₀ 值分别为 0.55、0.81 和 1.3 nM。 Vevorisertib trihydrochloride 可用于癌症的研究。

生物活性

Vevorisertib (ARQ 751) trihydrochloride is a selective, allosteric, pan-AKT and AKT1-E17K mutant inhibitors. Vevorisertib trihydrochloride potently inhibit phosphorylation of AKT. Vevorisertib trihydrochloride has Kd values of 1.2 nM and 8.6 nM for AKT1 and AKT1-E17K, respectively. Vevorisertib trihydrochloride has IC₅₀ values of 0.55, 0.81, and 1.3 nM for AKT1, AKT2, and AKT3, respectively. Vevorisertib trihydrochloride can be used for the research of cancer.

体外研究

Vevorisertib trihydrochloride (0, 12, 33, 111, 333, 1000 nM, 2 hours) inhibits phosphorylation of AKT1-E17K.
Vevorisertib trihydrochloride (1 μM for 2 hours; NIH 3T3 cells are transfected with either pcDNAAKT-WT-GFP or pcDNA-E17K-GFP) inhibits plasma membrane translocation of AKT-WT and AKT1-E17K irrespective of the presence of growth factors.
Vevorisertib trihydrochloride (5 μM) exhibites 57% inhibition of full-length AKT1.
Vevorisertib trihydrochloride (0, 0.012, 0.037, 0.11, 0.33, 1 μM; 2 hours) shows a dose-dependent effect on mTORC1 and AKT direct substrates including PRAS40, GSK3β, FOXO, BAD, and AS160 in cancer cell lines.
Vevorisertib trihydrochloride has anti-proliferative effect on esophageal, breast, and head and neck cancer cells (GI₅₀ < 1 μM).
Vevorisertib trihydrochloride exhibits strong anti-proliferative activity in PIK3CA mutant cell lines.
Vevorisertib trihydrochloride (MK-4440)/imatinib mesylate (IM) combination shows cell cycle arrest, and increases cell death of gastrointestinal stromal tumor (GIST) cells.
Vevorisertib trihydrochloride exhibits strong anti-proliferative activity in PIK3CA mutant cell lines:

Breast Cancer Cell Lines	GI₅₀ (nM)	PIK3CA	ER	PR	HER2
T47D	1.05	H1047R	+	+	-
EFM-19	1.54	H1047R	+	+	-
MCF-7	2.20	E545K	+	+	-
BT474	3.25	K111N	+	+	+
MDA-MB-453	6.05	H1047R	-	-	+

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Western Blot Analysis

Cell Line:	293T cells (transiently transfected with pcDNA-E17K-GFP)
Concentration:	0, 12, 33, 111, 333, 1000 nM
Incubation Time:	2 hours
Result:	Inhibited phosphorylation of AKT1-E17K.

Western Blot Analysis

Cell Line:	Cancer cell lines: MDA-MB 453 (PIK3CAH1047R; Her2 amp), NCI-H1650 (PTEN null), KU-19-19 (AKT1-E17K&E49K; NRas Q61R)
Concentration:	0, 0.012, 0.037, 0.11, 0.33, 1 μM
Incubation Time:	2 hours
Result:	Showed a dose-dependent effect on mTORC1 and AKT direct substrates including PRAS40, GSK3β, FOXO, BAD, and AS160.

体内研究
(In Vivo)

Vevorisertib trihydrochloride (25, 50 and 75 mg/kg; p.o.; 5 days dosing followed by a 4 day dosing holiday for 20 days) shows potent tumor growth inhibition of 68, 78 and 98%, respectively.
Vevorisertib trihydrochloride (5, 10, 20, 40, 80, and 120 mg/kg; p.o. daily for ten days) shows tumor growth inhibition of 29, 33, 50, 73, 83, and 92%, respectively.
Vevorisertib trihydrochloride reachs C_max plasma concentrations of ≥2 μM.
Vevorisertib trihydrochloride is generally well-tolerated at dose levels up to 120 mg/kg.
Vevorisertib trihydrochloride (MK-4440)/IM combination shows superior efficacy in an IM-sensitive preclinical model of GIST compared with either single agent.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Endometrial PDX mouse xenograft models (AKT1-E17K mutation tumor fragments subcutaneously implanted in athymic nude mice; tumor volume of approximately 200 mm³)
Dosage:	25, 50 and 75 mg/kg
Administration:	p.o.; 5 days dosing followed by a 4 day dosing holiday for 20 days
Result:	Showed potent tumor growth inhibition of 68, 78 and 98%, respectively.

Animal Model:	AN3CA mouse xenograft models (female NCr nu/nu mice with 250 mm³ tumors size)
Dosage:	5, 10, 20, 40, 80, and 120 mg/kg
Administration:	p.o.; daily for ten days
Result:	Showed tumor growth inhibition of 29, 33, 50, 73, 83, and 92%, respectively.

体内研究

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Endometrial PDX mouse xenograft models (AKT1-E17K mutation tumor fragments subcutaneously implanted in athymic nude mice; tumor volume of approximately 200 mm³)
Dosage:	25, 50 and 75 mg/kg
Administration:	p.o.; 5 days dosing followed by a 4 day dosing holiday for 20 days
Result:	Showed potent tumor growth inhibition of 68, 78 and 98%, respectively.

Animal Model:	AN3CA mouse xenograft models (female NCr nu/nu mice with 250 mm³ tumors size)
Dosage:	5, 10, 20, 40, 80, and 120 mg/kg
Administration:	p.o.; daily for ten days
Result:	Showed tumor growth inhibition of 29, 33, 50, 73, 83, and 92%, respectively.

体内研究

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:	Endometrial PDX mouse xenograft models (AKT1-E17K mutation tumor fragments subcutaneously implanted in athymic nude mice; tumor volume of approximately 200 mm³)
Dosage:	25, 50 and 75 mg/kg
Administration:	p.o.; 5 days dosing followed by a 4 day dosing holiday for 20 days
Result:	Showed potent tumor growth inhibition of 68, 78 and 98%, respectively.

Animal Model:	AN3CA mouse xenograft models (female NCr nu/nu mice with 250 mm³ tumors size)
Dosage:	5, 10, 20, 40, 80, and 120 mg/kg
Administration:	p.o.; daily for ten days
Result:	Showed tumor growth inhibition of 29, 33, 50, 73, 83, and 92%, respectively.

性状

Solid

溶解性数据

In Vitro:

DMSO : 150 mg/mL (215.48 mM; Need ultrasonic)

H₂O : 25 mg/mL (35.91 mM; ultrasonic and warming and heat to 60°C)

配制储备液

浓度溶剂体积质量	1 mg	5 mg	10 mg

1 mM	1.4366 mL	7.1828 mL	14.3655 mL
5 mM	0.2873 mL	1.4366 mL	2.8731 mL
10 mM	0.1437 mL	0.7183 mL	1.4366 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 (sealed storage, away from moisture)。-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: ≥ 5.25 mg/mL (7.54 mM); Clear solution

此方案可获得 ≥ 5.25 mg/mL (7.54 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 52.5 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: ≥ 5.25 mg/mL (7.54 mM); Clear solution

此方案可获得 ≥ 5.25 mg/mL (7.54 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 52.5 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