Jason Murphy

TL;DR: The RNA endonuclease CPSF3 was identified as the cellular efficacy target of the small molecule JTE-607, revealing pre-mRNA processing as a vulnerability in cancers such as Ewing’s sarcoma that are characterized by aberrant transcription.

TL;DR: JDQ443 is a structurally unique, covalent inhibitor of GDP-bound KRASG12C that forms novel interactions with the switch II pocket and demonstrates selective antiproliferative activity in KRAS G 12C-mutated cell lines, including those with G12C/H95 double mutations.

TL;DR: Cyclomarin A is a rare example of a natural product with two distinct and specific modes of action, and the identification of its molecular target, diadenosine triphosphate hydrolase (PfAp3Aase), by chemical proteomics validate PfAp 3Aase as a new drug target for the treatment of malaria.

TL;DR: It is shown that it is possible to confer high kinase selectivity to a promiscuous ATP-competitive inhibitor by tethering it to an antibody mimetic fused to the self-labeling protein SNAPtag, and the generality of using antibody mimetics as components of bivalent inhibitors is demonstrated by generating a reagent that is selective for the activated state of the serine/threonine kinase ERK2.