Pifusertib hydrochloride TAS-117 hydrochloride|西域试剂

Pifusertib hydrochloride TAS-117 hydrochloride,98.96%

产品编号：Bellancom-19934A| 分子式：C₂₆H₂₅ClN₄O₂| 分子量：460.96

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	价格	库存与货期
Bellancom-19934A	￥6000.00	杭州北京（现货）
Bellancom-19934A	￥10500.00	杭州北京（现货）
Bellancom-19934A	￥22500.00	杭州北京（现货）

增值税发票√顺丰快递√订货电话：18601927057

Pifusertib hydrochloride TAS-117 hydrochloride

产品介绍

Pifusertib (TAS-117) hydrochloride 是一种有效、选择性、具有口服活性的别构 Akt 抑制剂 (对 Akt1、2 和 3 的 IC₅₀ 分别为 4.8、1.6 和 44 nM)。Pifusertib hydrochloride 激发抗骨髓瘤活性并增强蛋白酶体抑制诱导的致命内质网应激。Pifusertib hydrochloride 诱导细胞凋亡 (apoptosis) 和自噬 (autophagy)。

生物活性

Pifusertib (TAS-117) hydrochloride is a potent, selective, orally active allosteric Akt inhibitor (with IC₅₀s of 4.8, 1.6, and 44 nM for Akt1, 2, and 3, respectively). Pifusertib hydrochloride triggers anti-myeloma activities and enhances fatal endoplasmic reticulum (ER) stress induced by proteasome inhibition. Pifusertib hydrochloride induces apoptosis and autophagy.

体外研究

Pifusertib (1 μM; 6 hours) blocks basal phosphorylation of Akt and downstream p-FKHR/FKHRL1 in MM cells with high baseline p-Akt.
Pifusertib (0-10 μM; 72 hours) selectively inhibits Akt and induces cytotoxicity in MM cells with high baseline phosphorylation of Akt.
Pifusertib abrogates the cytoprotective effect of the bone marrow microenvironment associated with Akt inhibition in both MM cells and BMSCs. Pifusertib enhances Carfilzomib-induced cytotoxicity and fatal ER stress in MM cells. Pifusertib (0.5, 1 μM) triggers G0/G1 arrest followed by apoptosis, associated with induction of autophagy and endoplasmic reticulum stress response.
Pifusertib enhances bortezomib-induced cytotoxicity, associated with increased CHOP (a fatal ER-stress marker) and PARP cleavage and blockade of bortezomib-induced p-Akt, suggesting that Pifusertib augments Bortezomib-induced ER stress and apoptotic signaling.

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

Cell Viability Assay

Cell Line:	MM cell lines
Concentration:	0-10 μM
Incubation Time:	72 hours
Result:	Induced significant growth inhibition in MM cell lines with high baseline p-Akt, but not in cell lines with low baseline p-Akt.

Western Blot Analysis

Cell Line:	MM.1S, MM.1R, H929, and KMS11 cells
Concentration:	1 μM
Incubation Time:	6 hours
Result:	Blocked basal phosphorylation of Akt and downstream p-FKHR/FKHRL1 in MM cells with high baseline p-Akt, but did not inhibit autophosphorylation of PDK1 which phosphorylates Akt at Thr308.

体内研究
(In Vivo)

Pifusertib (12-16 mg/kg; p.o.; daily for 5 days a week, 21 days) inhibits tumor growth in murine xenograft models of human MM.
Pifusertib enhances bortezomib-induced MM cytotoxicity in vivo.

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

Animal Model:	SCID mice (xenograft models bearing MM.1S cells)
Dosage:	12, 16 mg/kg
Administration:	P.o.; daily for 5 days a week, 21 days
Result:	Significantly reduced MM.1S tumor growth versus vehicle control.

体内研究

Pifusertib (12-16 mg/kg; p.o.; daily for 5 days a week, 21 days) inhibits tumor growth in murine xenograft models of human MM.
Pifusertib enhances bortezomib-induced MM cytotoxicity in vivo.

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

Animal Model:	SCID mice (xenograft models bearing MM.1S cells)
Dosage:	12, 16 mg/kg
Administration:	P.o.; daily for 5 days a week, 21 days
Result:	Significantly reduced MM.1S tumor growth versus vehicle control.

体内研究

Pifusertib (12-16 mg/kg; p.o.; daily for 5 days a week, 21 days) inhibits tumor growth in murine xenograft models of human MM.
Pifusertib enhances bortezomib-induced MM cytotoxicity in vivo.

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

Animal Model:	SCID mice (xenograft models bearing MM.1S cells)
Dosage:	12, 16 mg/kg
Administration:	P.o.; daily for 5 days a week, 21 days
Result:	Significantly reduced MM.1S tumor growth versus vehicle control.

性状

Solid

溶解性数据

In Vitro:

DMSO : 62.5 mg/mL (135.59 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	2.1694 mL	10.8469 mL	21.6939 mL
5 mM	0.4339 mL	2.1694 mL	4.3388 mL
10 mM	0.2169 mL	1.0847 mL	2.1694 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: ≥ 2.08 mg/mL (4.51 mM); Clear solution

此方案可获得 ≥ 2.08 mg/mL (4.51 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 20.8 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: ≥ 2.08 mg/mL (4.51 mM); Clear solution

此方案可获得 ≥ 2.08 mg/mL (4.51 mM，饱和度未知) 的澄清溶液。
以 1 mL 工作液为例，取 100 μL 20.8 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
3.

请依序添加每种溶剂： 10% DMSO 90% corn oil
Solubility: ≥ 2.08 mg/mL (4.51 mM); Clear solution

此方案可获得 ≥ 2.08 mg/mL (4.51 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 20.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。