title: H3K36 methyltransferases as cancer drug targets: rationale and perspectives for inhibitor development.
abstract: Methylation at histone 3, lysine 36 (H3K36) is a conserved epigenetic mark regulating gene transcription, alternative splicing and DNA repair. Genes encoding H3K36 methyltransferases (KMTases) are commonly overexpressed, mutated or involved in chromosomal translocations in cancer. Molecular biology studies have demonstrated that H3K36 KMTases regulate oncogenic transcriptional programs. Structural studies of the catalytic SET domain of H3K36 KMTases have revealed intriguing opportunities for design of small molecule inhibitors. Nevertheless, potent inhibitors for most H3K36 KMTases have not yet been developed, underlining the challenges associated with this target class. As we now have strong evidence linking H3K36 KMTases to cancer, drug development efforts are predicted to yield novel compounds in the near future.
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Rogawski
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Jolanta
authors.initials: J
authors.lastname: Grembecka
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Cierpicki
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008780:Methyltransferases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D054852:Small Molecule Libraries; D008780:Methyltransferases
keywords: cancer; chromosomal translocation; epigenetics; gene expression; genome integrity; histone methyltransferase; oncogenes; protein–protein interactions; structure-based drug design