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