Discovery of BAY 2666605, a Molecular Glue for PDE3A and SLFN12.

ACS medicinal chemistry letters
Authors
Abstract

A subset of phosphodiesterase 3 (PDE3) inhibitors kills cancer cells that express both PDE3A and SLFN12 by inducing a protein-protein interaction between the two, triggering SLFN12 tRNase activity. Following discovery of the prototypical tool compound, , an improved compound, , was discovered to be potent in cells and active in several tumor models . More analogs were prepared and tested with the goal of increasing metabolic stability and decreasing PDE3 inhibition while maintaining the cellular activity of . This led to the discovery of , a compound optimized for clinical testing.

Year of Publication
2024
Journal
ACS medicinal chemistry letters
Volume
15
Issue
10
Pages
1662-1667
Date Published
10/2024
ISSN
1948-5875
DOI
10.1021/acsmedchemlett.4c00336
PubMed ID
39411532
Links