Identification of a new class of MDM2 inhibitor that inhibits growth of orthotopic pancreatic tumors in mice.

ABSTRACT:

Background & aims

The oncogene MDM2, which encodes an E3 ubiquitin ligase, is overexpressed in pancreatic cancers and is therefore a therapeutic target. Current inhibitors of MDM2 target the interaction between MDM2 and P53; these would have no effect on cancer cells that do not express full-length P53, including many pancreatic cancer cells. We searched for a compound that specifically inhibits MDM2 itself.

Methods

We performed a virtual screen and structure-based design to identify specific inhibitors of MDM2. We tested the activities of compounds identified on viability, proliferation, and protein levels of HPAC, Panc-1, AsPC-1, and Mia-Paca-2 pancreatic cancer cell lines. We tested whether intraperitoneal injections of one of the compounds identified affected growth of x

SUBMITTER: Wang W 

PROVIDER: S-EPMC4170027 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature