Small molecules which disrupt the prenylation of oncogenic small GTPases have been the focus of drug discovery efforts for many decades. To this end, the human geranylgeranyl pyrophosphate synthase (hGGPPS) is a promising, yet relatively underexplored target. We designed novel C-2 substituted thienopyrimidine-based bisphosphonate (C2-ThP-BP) which are potent and selective inhibitors of hGGPPS. These inhibitors induce target selective apoptosis of multiple myeloma (MM) cells and exhibit antimyeloma activity in vivo. The structure-activity relationship of these compounds, as well as their biological properties will be discussed.

Synthesis and evaluation of structurally diverse C-2-substituted thienopyrimidine-based inhibitors of the human geranylgeranyl pyrophosphate synthase

Fall 2022 abstracts, posters, and presentations will launch in mid-September.

ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.