Description
AT7867 is a potent and orally bioavailable inhibitor of Akt isoforms Akt1, 2, and 3 (IC
50s = 32, 17, and 47 nM, respectively). It also inhibits p70S6 kinase and PKA (IC
50s = 85 and 20 nM, respectively), but is without effect against a panel of other kinases. AT7867 inhibits growth and induces apoptosis in a variety of cancer cell lines
in vitro and suppresses tumor growth of PTEN-deficient xenografts in mice.
Uses
A potent Akt inhibitor with an IC50 of 17 nM. AT7867 also inhibits structurally related AGC kinases p70S6K and PKA with IC50s of 20 nM and 85 nM, respectively.
Definition
ChEBI: AT7867 is a member of the class of piperidines carrying two aryl substituents (4-chlorophenyl and 4-(pyrazol-4-yl)phenyl) at position 4. It has a role as an EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor and an antineoplastic agent. It is a member of pyrazoles, a member of piperidines and a member of monochlorobenzenes.
Enzyme inhibitor
This potent ATP-competitive inhibitor (FW = 337.85; CAS 857531-00-1; Solubility: 68 mg/mL DMSO, <1 mg/mL H2O), known systematically as 4- (4-(1H-pyrazol-4-yl)phenyl)-4-(4-chlorophenyl)piperidine, targets Akt1, Akt2 and Akt3 Protein Kinases B (or PKB), with IC50 values of 32 nM, 17 nM and 47 nM, respectively. AT7867 also inhibits the structurally related AGC kinases, p70S6K and PKA, with IC50 values of 20 nM and 85 nM, respectively.
References
grimshaw km, hunter lj, yap ta et al. at7867 is a potent and oral inhibitor of akt and p70 s6 kinase that induces pharmacodynamic changes and inhibits human tumor xenograft growth. mol cancer ther. 2010 may;9(5):1100-10.
