TAS-117 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 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 诱导细胞凋亡 (apoptosis) 和自噬 (autophagy)。
| 生物活性 | TAS-117 is a potent, selective, orally active allostericAktinhibitor (withIC50s of 4.8, 1.6, and 44 nM forAkt1, 2, and 3, respectively). TAS-117 triggers anti-myeloma activities and enhances fatal endoplasmic reticulum (ER) stress induced byproteasomeinhibition. TAS-117 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 cell lines | | Concentration: | 0-10 μM | | Incubation Time: | 72 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 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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