TAS-117

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

TAS-117 是一种高选择性、非 ATP 竞争性泛 Akt 抑制剂，对 Akt1/Akt2/Akt3 的 IC50 值分别为 4.8/1.6/44 nM。

TAS-117 is a highly selective, non-ATP competitive pan-Akt inhibitor with IC50 of 4.8/1.6/44 nM for Akt1/Akt2/Akt3 respectively; shows minimal inhibitory activities against others kinases including PI3K, PDK1, and mTOR; inhibits Akt kinase activity but not p-Akt, blocks basal phosphorylation of Akt and downstream p-FKHR/FKHRL1; induces significant cytotoxicity in MM cells associated with inhibition of IL6 secretion; triggers apoptosis and autophagy, induces ER stress response, inhibits human MM cell growth in murine xenograft models.Solid Tumors Phase 1 Clinical.

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. 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 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.

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. 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.

TAS117

PI3K/Akt/mTOR signaling

Akt

Akt

Cancer

Solid Tumors

1402602-94-1

424.504

C26H24N4O2

>98% (HPLC)

——

C[C@]1(O)C[C@@](N)(C2=CC=C(C=C2)C3=C(C4=CC=CC=C4)N5COC6=CC=NC=C6C5=N3)C1

Trans-3-amino-1methyl-3-[4-(3-phenyl-5H-imidazo[1,2-c]pyrido[3,4-e][1,3]oxazin-2-yl)phenyl]-cyclobutanol

(-20℃)

With Ice Pack

≥ 2 years