MedKoo product information:

 PF-AKT400

Description of PF-AKT400: PF-AKT400 is an APT competitor inhibitor of AKR kinase. This compound was first described as compound 42  in J. Med. Chem. 2010, 53, 4615–4622 by a group of Pfizer scientists. The paper describes the design and synthesis of novel, ATP-competitive Akt inhibitors from an elaborated 3-aminopyrrolidine scaffold. Key findings include the discovery of an initial lead that was modestly selective and medicinal chemistry optimization of that lead to provide more selective analogues. Analysis of the data suggested that highly lipophilic analogues would likely suffer from poor overall properties. Central to the discussion is the concept of optimization of lipophilic efficiency and the ability to balance overall druglike propeties with the careful control of lipophilicity in the lead series. Discovery of the nonracemic amide series and subsequent modification produced an advanced analogue that performed well in advanced preclinical assays, including xenograft tumor growth inhibition studies, and this analogue was nominated for clinical development. The compound has no official name, has molecule weight 400.43. We temporally call this compound as PF-AKT400.

Current developer:  Pfizer

1: Freeman-Cook KD, Autry C, Borzillo G, Gordon D, Barbacci-Tobin E, Bernardo V, Briere D, Clark T, Corbett M, Jakubczak J, Kakar S, Knauth E, Lippa B, Luzzio MJ, Mansour M, Martinelli G, Marx M, Nelson K, Pandit J, Rajamohan F, Robinson S, Subramanyam C, Wei L, Wythes M, Morris J. Design of selective, ATP-competitive inhibitors of Akt. J Med Chem. 2010 Jun 24;53(12):4615-22. Erratum in: J Med
Chem. 2010 Aug 12;53(15):5895. PubMed PMID: 20481595.