A-674563 (free base)

White to off-white solid. Soluble in DMF (20mg/ml) or DMSO (10mg/ml). Chemical. CAS: 552325-73-2. Formula: C22H22N4O. MW: 358.4. Synthetic. A-674563 is a potent, ATP-competitive, reversible and orally available Akt1 inhibitor with an IC50 of 11nM. Binds to the ATP site of the AKT kinase domain, inhibiting AKT-catalyzed phosphorylation activity. Also inhibits PKA and CDK2 with IC50 values of 16nM and 46nM, respectively. 10- to >1,800-fold selective for Akt1 versus additional kinases in the CMGC, CAMK and TK families. Anticancer compound. Reduces phosphorylation of Akt downstream targets in cells and slows proliferation of tumor cells in vitro with an EC50 value of 0.4µM. Shown to decrease tumor growth in mouse tumor xenograft models. Decreased sphingosine kinase 1 (SphK1) activity in AML cells to deplete pro-survival sphingosine-1-phosphate (S1P) and boost pro-apoptotic ceramide production.