Protein lysine methyltransferases (PKMTs) regulate numerous epigenetic processes, and there is increasing evidence for their dysregulation playing a role in cancer through downregulation of tumor suppressors or upregulation of oncogenes that promote cancer progression and proliferation. There is tremendous interest in utilizing a variety of selective inhibitors to illuminate the role of PKMTs in disease and develop potential therapeutics, but few such inhibitors exist.
Like kinases, PKMTs are conformationally heterogeneous, providing an opportunity to exploit binding to distinct conformations to achieve selectivity. Funded by a STARR Cancer Consortium grant with Minkui Luo, we are working to apply the same methodology used for designing selective kinase inhibitors to aid the Luo lab in developing useful chemical probes for elcudiating PKMT function.
Minkui Luo (MSKCC): Synthesis of novel selective protein methyltransferase inhibitors
Rafal Wiewiora (TPCB Graduate Student)