Progress in the Development of Lysine Methyltransferase SETD8 Inhibitors

被引：20

作者：

Milite, Ciro ^{[1
,2
]}

Feoli, Alessandra ^{[1
,2
,3
]}

Viviano, Monica ^{[1
,2
]}

Rescigno, Donatella ^{[1
,2
,3
]}

Mai, Antonello ^{[4
]}

Castellano, Sabrina ^{[1
,2
,5
]}

Sbardella, Gianluca ^{[1
,2
]}

机构：

[1] Univ Salerno, Dipartimento Farm, Via Giovanni Paolo 2 132, I-84084 Fisciano, SA, Italy

[2] Univ Salerno, Epigenet Med Chem Lab, Via Giovanni Paolo 2 132, I-84084 Fisciano, SA, Italy

[3] Univ Salerno, Programma Dottorato Ric Sci Farmaco, Via Giovanni Paolo 2 132, I-84084 Fisciano, SA, Italy

[4] Sapienza Univ Roma, Ist Pasteur, Fdn Cenci Bolognetti, Dipartimento Chim & Tecnol Farmaco, Ple A Moro 5, I-500185 Rome, Italy

[5] Univ Salerno, Dipartimento Med & Chirurg, Via Giovanni Paolo 2 132, I-84084 Fisciano, SA, Italy

来源：

CHEMMEDCHEM | 2016年 / 11卷 / 16期

关键词：

epigenetics; inhibitors; methylation; SETD8; transferases; PR-SET7 HISTONE METHYLTRANSFERASE; SMALL-MOLECULE INHIBITORS; CELLULAR-ACTIVITY; ARGININE METHYLTRANSFERASES; PROTEIN METHYLTRANSFERASES; MARINE SEDIMENT; CHEMICAL PROBE; NAHUOIC ACID; S PHASE; H4;

D O I：

10.1002/cmdc.201600272

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

SETD8/SET8/Pr-SET7/KMT5A is the only known lysine methyltransferase that monomethylates lysine20 of histone H4 (H4K20) invivo. 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.

引用

页码：1680 / 1685

页数：6

共 55 条

[1] PR-Set7 and H4K20me1: at the crossroads of genome integrity, cell cycle, chromosome condensation, and transcription [J].