Epigenetic cancer targets

Protein methyltransferase NSD1 (pdbid 4h12)

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.

RESOURCES

Simulating protein methyltransferases on Folding@home

COLLABORATORS

Minkui Luo (MSKCC): Synthesis of novel selective protein methyltransferase inhibitors

PERSONNEL

Rafal Wiewiora (TPCB Graduate Student)

FUNDING

STARR CANCER CONSORTIUM