title: Progress in the Development of Lysine Methyltransferase SETD8 Inhibitors.
abstract: SETD8/SET8/Pr-SET7/KMT5A is the only known lysine methyltransferase that monomethylates lysine 20 of histone H4 (H4K20) in vivo. The methyltransferase activity of SETD8 has been implicated in many essential cellular processes, including DNA replication, DNA damage response, transcription modulation, and cell cycle regulation. In addition to H4K20, SETD8 monomethylates non-histone substrates including proliferating cell nuclear antigen and p53. During the past decade, different structural classes of inhibitors targeting various lysine methyltransferases have been designed and developed. However, the development of SETD8 inhibitors is still in its infancy. This review covers the progress made to date in inhibiting the activity of SETD8 by small molecules, with an emphasis on their discovery, selectivity over other methyltransferases, and cellular activity.
authors.affiliation: Dipartimento di Farmacia, Università degli Studi di Salerno, Via Giovanni Paolo II 132, 84084, Fisciano, SA, Italy.|Epigenetic Med Chem Lab, Università degli Studi di Salerno, Via Giovanni Paolo II 132, 84084, Fisciano, SA, Italy.
authors.forename: Ciro
authors.identifier: 0000-0003-1000-1376
authors.initials: C
authors.lastname: Milite
authors.affiliation: Dipartimento di Farmacia, Università degli Studi di Salerno, Via Giovanni Paolo II 132, 84084, Fisciano, SA, Italy.|Epigenetic Med Chem Lab, Università degli Studi di Salerno, Via Giovanni Paolo II 132, 84084, Fisciano, SA, Italy.|Programma di Dottorato di Ricerca in Scienze del Farmaco, Università degli studi di Salerno, Via Giovanni Paolo II 132, 84084, Fisciano, SA, Italy.
authors.forename: Alessandra
authors.identifier: 0000-0002-8960-7858
authors.initials: A
authors.lastname: Feoli
authors.affiliation: Dipartimento di Farmacia, Università degli Studi di Salerno, Via Giovanni Paolo II 132, 84084, Fisciano, SA, Italy.|Epigenetic Med Chem Lab, Università degli Studi di Salerno, Via Giovanni Paolo II 132, 84084, Fisciano, SA, Italy.
authors.forename: Monica
authors.identifier: 0000-0003-1118-790X
authors.initials: M
authors.lastname: Viviano
authors.affiliation: Dipartimento di Farmacia, Università degli Studi di Salerno, Via Giovanni Paolo II 132, 84084, Fisciano, SA, Italy.|Epigenetic Med Chem Lab, Università degli Studi di Salerno, Via Giovanni Paolo II 132, 84084, Fisciano, SA, Italy.|Programma di Dottorato di Ricerca in Scienze del Farmaco, Università degli studi di Salerno, Via Giovanni Paolo II 132, 84084, Fisciano, SA, Italy.
authors.forename: Donatella
authors.identifier: 0000-0003-3292-6820
authors.initials: D
authors.lastname: Rescigno
authors.affiliation: Istituto Pasteur - Fondazione Cenci Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, "Sapienza" Università di Roma, P.le A. Moro 5, 00185, Rome, Italy.
authors.forename: Antonello
authors.identifier: 0000-0001-9176-2382
authors.initials: A
authors.lastname: Mai
authors.affiliation: Dipartimento di Farmacia, Università degli Studi di Salerno, Via Giovanni Paolo II 132, 84084, Fisciano, SA, Italy.|Epigenetic Med Chem Lab, Università degli Studi di Salerno, Via Giovanni Paolo II 132, 84084, Fisciano, SA, Italy.|Dipartimento di Medicina e Chirurgia, Università degli Studi di Salerno, Via Giovanni Paolo II 132, 84084, Fisciano, SA, Italy.
authors.forename: Sabrina
authors.identifier: 0000-0002-7449-3704
authors.initials: S
authors.lastname: Castellano
authors.affiliation: Dipartimento di Farmacia, Università degli Studi di Salerno, Via Giovanni Paolo II 132, 84084, Fisciano, SA, Italy. gsbardella@unisa.it.|Epigenetic Med Chem Lab, Università degli Studi di Salerno, Via Giovanni Paolo II 132, 84084, Fisciano, SA, Italy. gsbardella@unisa.it.
authors.forename: Gianluca
authors.identifier: 0000-0003-0748-1145
authors.initials: G
authors.lastname: Sbardella
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011495:Histone-Lysine N-Methyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D011495:Histone-Lysine N-Methyltransferase; C470730:KMT5A protein, human
keywords: SETD8; epigenetics; inhibitors; methylation; transferases