Transition state analogue of MTAP extends lifespan of APC^Min/+ mice.

ABSTRACT: A mouse model of human Familial Adenomatous Polyposis responds favorably to pharmacological inhibition of 5'-methylthioadenosine phosphorylase (MTAP). Methylthio-DADMe-Immucillin-A (MTDIA) is an orally available, transition state analogue inhibitor of MTAP. 5'-Methylthioadenosine (MTA), the substrate for MTAP, is formed in polyamine synthesis and is recycled by MTAP to S-adenosyl-L-methionine (SAM) via salvage pathways. MTDIA treatment causes accumulation of MTA, which inhibits growth of human head and neck (FaDu) and lung (H359, A549) cancers in immunocompromised mouse models. We investigated the efficacy of oral MTDIA as an anti-cancer therapeutic for intestinal adenomas in immunocompetent APC^Min/+ mice, a murine model of human Familial Adenomatous Polyposis. Tumors in APC

SUBMITTER: Firestone RS 

PROVIDER: S-EPMC8065027 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature