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Vevorisertib trihydrochloride
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。
Vevorisertib trihydrochloride图片
CAS NO:1416775-08-0
包装与价格:
包装价格(元)
5mg电议
10mg电议
50mg电议
100mg电议

产品名称
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-AKTand AKT1-E17K mutant inhibitors. Vevorisertib trihydrochloride potently inhibit phosphorylation ofAKT. Vevorisertib trihydrochloride hasKdvalues of 1.2 nM and 8.6 nM forAKT1and AKT1-E17K, respectively. Vevorisertib trihydrochloride hasIC50values of 0.55, 0.81, and 1.3 nM forAKT1,AKT2, andAKT3, respectively. Vevorisertib trihydrochloride can be used for the research ofcancer[1].

IC50& Target[1]

Akt1

0.55 nM (IC50)

Akt2

0.81 nM (IC50)

Akt3

1.31 nM (IC50)

Akt1

1.2 nM (Kd)

Akt1E17K

8.6 nM (Kd)

体外研究
(In Vitro)

Vevorisertib trihydrochloride (0, 12, 33, 111, 333, 1000 nM, 2 hours) inhibits phosphorylation of AKT1-E17K[1].
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[1].
Vevorisertib trihydrochloride (5 μM) exhibites 57% inhibition of full-length AKT1[1].
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[1].
Vevorisertib trihydrochloride has anti-proliferative effect on esophageal, breast, and head and neck cancer cells (GI50< 1 μM)[1].
Vevorisertib trihydrochloride exhibits strong anti-proliferative activity in PIK3CA mutant cell lines[1].
Vevorisertib trihydrochloride (MK-4440)/imatinib mesylate (IM) combination shows cell cycle arrest, and increases cell death of gastrointestinal stromal tumor (GIST) cells[2].
Vevorisertib trihydrochloride exhibits strong anti-proliferative activity in PIK3CA mutant cell lines[1]:

Breast Cancer Cell LinesGI50(nM)PIK3CAERPRHER2
T47D1.05H1047R++-
EFM-191.54H1047R++-
MCF-72.20E545K++-
BT4743.25K111N+++
MDA-MB-4536.05H1047R--+

Western Blot Analysis[1]

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[1]

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[1].
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[1].
Vevorisertib trihydrochloride reachs Cmaxplasma concentrations of ≥2 μM[1].
Vevorisertib trihydrochloride is generally well-tolerated at dose levels up to 120 mg/kg[1].
Vevorisertib trihydrochloride (MK-4440)/IM combination shows superior efficacy in an IM-sensitive preclinical model of GIST compared with either single agent[2].

Animal Model:Endometrial PDX mouse xenograft models (AKT1-E17K mutation tumor fragments subcutaneously implanted in athymic nude mice; tumor volume of approximately 200 mm3)[1]
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 NCrnu/numice with 250 mm3tumors size)[1]
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.
Clinical Trial
分子量

696.11

性状

Solid

Formula

C35H41Cl3N8O

CAS 号

1416775-08-0

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

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℃)

配制储备液
浓度溶剂体积质量1 mg5 mg10 mg
1 mM1.4366 mL7.1828 mL14.3655 mL
5 mM0.2873 mL1.4366 mL2.8731 mL
10 mM0.1437 mL0.7183 mL1.4366 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℃, 6 months; -20℃, 1 month (sealed storage, away from moisture)。-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: ≥ 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-CDin 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 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。