Azole-based inhibitors of AKT/PKB for the treatment of cancer.
2010
Abstract Through a combination of screening and structure-based rational design, we have discovered a series of N 1 -(5-(heterocyclyl)-thiazol-2-yl)-3-(4-trifluoromethylphenyl)-1,2-propanediamines that were developed into potent ATP competitive inhibitors of AKT. Studies of linker strand-binding adenine isosteres identified SAR trends in potency and selectivity that were consistent with binding interactions observed in structures of the inhibitors bound to AKT1 and to the counter-screening target PKA. One compound was shown to have acceptable pharmacokinetic properties and to be a potent inhibitor of AKT signaling and of in vivo xenograft tumor growth in a preclinical model of glioblastoma.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
21
References
14
Citations
NaN
KQI