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)。TAS-117 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。TAS-117 hydrochloride 诱导细胞凋亡 (apoptosis) 和自噬 (autophagy)。
生物活性 | TAS-117 hydrochloride is a potent, selective, orally active allostericAktinhibitor (withIC50s of 4.8, 1.6, and 44 nM forAkt1, 2, and 3, respectively). TAS-117 hydrochloride triggers anti-myeloma activities and enhances fatal endoplasmic reticulum (ER) stress induced byproteasomeinhibition. TAS-117 hydrochloride inducesapoptosisandautophagy[1]. |
IC50& Target[1] | Akt1 4.8 nM (IC50) | Akt2 1.6 nM (IC50) | Akt3 44 nM (IC50) |
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体外研究 (In Vitro) | TAS-117 (1 μM; 6 hours) blocks basal phosphorylation of Akt and downstream p-FKHR/FKHRL1 in MM cells with high baseline p-Akt[1]. TAS-117 (0-10 μM; 72 hours) selectively inhibits Akt and induces cytotoxicity in MM cells with high baseline phosphorylation of Akt[1]. TAS-117 abrogates the cytoprotective effect of the bone marrow microenvironment associated with Akt inhibition in both MM cells and BMSCs. TAS-117 enhances Carfilzomib-induced cytotoxicity and fatal ER stress in MM cells. TAS-117 (0.5, 1 μM) triggers G0/G1 arrest followed by apoptosis, associated with induction of autophagy and endoplasmic reticulum stress response[1]. TAS-117 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 TAS-117 augments Bortezomib-induced ER stress and apoptotic signaling[1].
Cell Viability Assay[1] 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[1] 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. |
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体内研究 (In Vivo) | TAS-117 (12-16 mg/kg; p.o.; daily for 5 days a week, 21 days) inhibits tumor growth in murine xenograft models of human MM[1]. TAS-117 enhances bortezomib-induced MM cytotoxicity in vivo[1].
Animal Model: | SCID mice (xenograft models bearing MM.1S cells)[1] | 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. |
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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 : 62.5 mg/mL(135.59 mM;ultrasonic and warming and heat to 60℃) 配制储备液 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℃, 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: ≥ 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。 2. 请依序添加每种溶剂: 10% DMSO 90% (20%SBE-β-CDin 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 μL20% 的 SBE-β-CD 生理盐水水溶液中,混合均匀。 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。 *以上所有助溶剂都可在本网站选购。
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