TAS-117

Cas No.:	1402602-94-1
Chemical Name:	TAS-117
Synonyms:	QI52W1ZIIB;TAS 117;(1r,3r)-3-amino-1-methyl-3-(4-(3-phenyl-5H-imidazo[1,2-c]pyrido[3,4-e][1,3]oxazin-2-yl)phenyl)cyclobutan-1-ol;BDBM126588;DB15054;SB17256;J3.460.963B;US8772283, 32;Cyclobutanol, 3-amino-1-methyl-3-(4-(3-phenyl-5H-imidazo(1,2-C)pyrido(3,4-E)(1,3)oxazin-2-yl)phenyl)-, trans-;trans-3-Amino-1-methyl-3-(4-(3-phenyl-5H-imidazo(1,2-C)pyrido(3,4-E)(1,3)oxazin-2-yl)phenyl)cyc;Unii-QI52W1ziib;Pifusertib;TAS-117
SMILES:	OC1(C)CC(C2C=CC(C3=C(C4C=CC=CC=4)N4COC5C=CN=CC=5C4=N3)=CC=2)(C1)N
Formula:	C26H24N4O2
M.Wt:	424.494365692139
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	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 TumorsPhase 1 Clinical
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.
In Vitro:	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.