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Novel p53/mdm2 and p53/mdm4 antagonists

詳細技術說明

None

*Abstract

BackgroundThe protein-protein interaction (PPI) between the transcription factor p53 and its negative regulator, Mdm2, is a major target in current cancer drug discovery. Disrupting this interation was shown to restore the wild type p53 activity and drive cancer cells selectively into apoptosis.TechnologyInvestigators have discovered novel, small molecule antagonists of the p53-Mdm2 complex. Two new scaffolds have been developed that bind tightly to mdm2 and thus can antagonize p53/mdm2 protein interaction. Novel p53/mdm2 antagnoists are desired in order to improve PKPD properties as well as therapeutic outcome of their anti cancer properties.The compounds of the two scaffolds show binding affinity to mdm2 in the uM to nM range and also show apoptosis induction in cancer cell lines.Application* Treatment or prevention of cancer especially relapsed/refractory acute myeloid and lymphoid leukemia and refractory chronic lymphocytic leukemia/small cell lymphocytic lymphomaAdvantages1. Better protein and cell based activity while having good physicochemical properties such as: a. water solubility b. cell permeation c. lipophilicity d. polar surface area e. molecular weight f. metabolic stability g. number of rotatable bonds.PCT patent application filed

*Principal Investigation

Name: Alexander Doemling

Department: Pharm-Pharmaceutical Science

國家/地區

美國