A-674563

Three related forms of the kinase Akt (1, 2, 3, also known as protein kinase B isoforms PKBalpha, beta, gamma) modulate cell proliferation, metabolism, and survival, as well as angiogenesis. A-674563 is an orally available, ATP-competitive, and reversible inhibitor of Akt (Ki = 11 nM for Akt1). It shows inhibitory activity against PKA and Cdk2 with IC50 values of 16 and 46 nM, respectively, but is 10- to >1,800-fold selective for Akt1 versus additional kinases in the CMGC, CAMK, and TK families. A-674563 reduces phosphorylation of Akt downstream targets in cells and slows proliferation of tumor cells in vitro with an EC50 value of 0.4 µM. In vivo, 40 mg/kg/day A-674563 in combination with 15 mg/kg/day paclitaxel (Cay-10461) was shown to decrease tumor growth in a PC-3 prostate cancer mouse xenograft model.Formal Name: alphaS-[[[5-(3-methyl-1H-indazol-5-yl)-3-pyridinyl]oxy]methyl]-benzeneethanamine. CAS Number: 552325-73-2. Molecular Formula: C22H22N4O. Formula Weight: 358.4. Purity: >95%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 20 mg/ml, DMF:PBS(pH 7.2)(1:1): 0.5 mg/ml, DMSO: 15 mg/ml, Ethanol: 10 mg/ml. lambdamax: 245, 299 nm. SMILES: CC1=NNC(C1=C2)=CC=C2C3=CN=CC(OC[C@@H](N)CC4=CC=CC=C4)=C3. InChi Code: InChI=1S/C22H22N4O/c1-15-21-11-17(7-8-22(21)26-25-15)18-10-20(13-24-12-18)27-14-19(23)9-16-5-3-2-4-6-16/h2-8,10-13,19H,9,14,23H2,1H3,(H,25,26)/t19-/m0/s1. InChi Key: BPNUQXPIQBZCMR-IBGZPJMESA-N.