生物活性

• 靶点

  Akt2 Ki:2nM

  Akt3 Ki:2.6nM

  Akt1 Ki:0.08nM

• 描述Akt (protein kinase B) is a master regulator of cell survival in response to growth factors. In human cancers, Akt plays a pivotal role in cell growth, apoptosis inhibition, protein synthesis, and glucose and fatty acid metabolism by phosphorylating its substrates, including CDK2, FOXO, GSK-3beta, S6 kinase, and mTOR. Afuresertib, a thiophenecarboxamide derivative, is a catalytic ATP‐competitive inhibitor of AKT1, AKT2, AKT3 with Ki values of 0.08 nM, 2 nM, and 2.6 nM. Afuresertib, an ATP‐competitive specific Akt inhibitor, exerted tumor‐specific effects on MPM cells. Afuresertib significantly increased caspase‐3 and caspase‐7 activities and apoptotic cell number among ACC-MESO-4 and MSTO-211H cells. Moreover, Afuresertib strongly arrested the cell cycle in the G1 phase. Cells treated with Afuresertib show decreased phosphorylation of several substrates downstream of AKT. Afuresertib at 5 μmol/L for 24h clearly suppressed the migration of ACC-MESO-4 and MSTO-211H cells. In a phase IIa study of Afuresertib, patients were treated with oral Afuresertib (125 mg/d) for over 28 weeks, it was showed that Afuresertib had clinical activity in some patients with newly diagnosed and advanced LCH.

• 动物研究
  剂量	Mice: 10 mg/kg - 100 mg/kg[1] (p.o.)
  给药途径	p.o.