A-674563

A-674563 is an orally active, potent, and selective small molecule inhibitor of Akt1 (protein kinase B), with a Ki of 11 nM and IC50 of 14 nM[1][5][7]. It also inhibits protein kinase A (PKA; IC50 = 16 nM), cyclin-dependent kinase 2 (CDK2; IC50 = 46 nM), and has demonstrated >30-fold selectivity for Akt1 over protein kinase C[3][7]. Mechanistically, A‑674563 binds to the ATP-binding site of Akt1 and reduces phosphorylation of downstream targets such as GSK3α/β, FOXO3, TSC2, mTOR, S6 ribosomal protein, MDM2, and others[5][6]. In preclinical studies it induces G2 cell cycle arrest and apoptosis in tumor cells including soft tissue sarcoma lines. It has shown efficacy in reducing proliferation in non-small cell lung cancer (NSCLC) models—where it was more effective than pan-AKT inhibitors—and acute myeloid leukemia models with FLT3‑ITD mutations via dual inhibition of AKT and FLT3 kinases[4][8]. The compound is experimental and primarily used as a research tool to study AKT signaling pathways.

Other names

(alphaS)-alpha-(((5-(3-Methyl-1H-indazol-5-yl)-3-pyridinyl)oxy)methyl)benzeneethanamine(2S)-1-(5-(3-methyl-1H-indazol-5-yl)pyridin-3-yloxy)-3-phenylpropan-2-amine