CCT128930?HCl?is a potent, selective, novel and ATP-competitive inhibitor for AKT2 (IC50= 6 nM). It also has 28-fold and 20-fold selectivity over PKA kinase (IC50= 168 nM) and p70S6K (IC50= 120 nM), respectively.
Akt (protein kinase B) is a serine/threonine-specific protein kinase that plays a key role in multiple cellular processes such as glucose metabolism, apoptosis, cell proliferation, transcription and cell migration.
In multi tumor cell line, CCT128930?HCl?showed antiproliferative effect and blocked the phosphorylation of various Akt substrates. In PTEN-null human glioblastoma cells (U87MG), CCT128930?HCl?treatment led to a G1 arrest associated with Akt pathway suppression. [1]
In U87MG tumor xenografts, CCT128930?HCl?inhibited the phosphorylation of Akt downstream biomarkers. In U87MG, HER-2 positive and IK3CA-mutant BT474 human breast cancer xenografts, antitumor activity were recorded as tumor volume decreased. CCT128930?HCl-treated mouse whisker folliciles in vivo and human hair follicles treated ex vivo exerted prominent reduction in pThr246 PRAS40. [1]
Reference:
1. Yap TA, Walton MI, Hunter LJ et al.? Preclinical pharmacology, antitumor activity, and development of pharmacodynamic markers for the novel, potent AKT inhibitor CCT128930. Mol Cancer Ther. 2011 Feb;10(2):360-71.
