TAS-117 hydrochloride - CAS# 2930090-28-9

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). TAS-117 hydrochloride triggers anti-myeloma activities and enhances fatal endoplasmic reticulum (ER) stress induced by proteasome inhibition. TAS-117 hydrochloride induces apoptosis and autophagy.

Product information

CAS Number: 2930090-28-9

Molecular Weight: 460.96

Formula: C26H25ClN4O2

Chemical Name: (1r,3s)-3-amino-1-methyl-3-(4-{5-phenyl-8-oxa-3,6,12-triazatricyclo[7.4.0.0²,⁶]trideca-1(13),2,4,9,11-pentaen-4-yl}phenyl)cyclobutan-1-ol hydrochloride

Smiles: Cl.C[C@@]1(O)C[C@@](N)(C1)C1C=CC(=CC=1)C1N=C2C3=CN=CC=C3OCN2C=1C1C=CC=CC=1

InChiKey: JPKYUPVHSPWRNX-RHJJCEFHSA-N

InChi: InChI=1S/C26H24N4O2.ClH/c1-25(31)14-26(27,15-25)19-9-7-17(8-10-19)22-23(18-5-3-2-4-6-18)30-16-32-21-11-12-28-13-20(21)24(30)29-22;/h2-13,31H,14-16,27H2,1H3;1H/t25-,26-;

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : 62.5 mg/mL (135.59 mM; ultrasonic and warming and heat to 60°C).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

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. TAS-117 (0-10 μM; 72 hours) selectively inhibits Akt and induces cytotoxicity in MM cells with high baseline phosphorylation of Akt. 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. 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.

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. TAS-117 enhances bortezomib-induced MM cytotoxicity in vivo.

Products are for research use only. Not for human use.