Structure-Activity Relationship Studies on (R)-PFI-2 Analogues as Inhibitors of Histone Lysine Methyltransferase SETD7.
ChemMedChem
; 13(14): 1405-1413, 2018 07 18.
Article
em En
| MEDLINE
| ID: mdl-29869845
ABSTRACT
SETD7 is a histone H3K4 lysine methyltransferase involved in human gene regulation. Aberrant expression of SETD7 has been associated with various diseases, including cancer. Therefore, SETD7 is considered a good target for the development of new epigenetic drugs. To date, few selective small-molecule inhibitors have been reported that target SETD7, the most potent being (R)-PFI-2. Herein we report structure-activity relationship studies on (R)-PFI-2 and its analogues. A library of 29 structural analogues of (R)-PFI-2 was synthesized and evaluated for inhibition of recombinantly expressed human SETD7. The key interactions were found to be a salt bridge and a hydrogen bond formed between (R)-PFI-2's NH2+ group and SETD7's Asp256 and His252 residue, respectively.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pirrolidinas
/
Sulfonamidas
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Histona-Lisina N-Metiltransferase
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Tetra-Hidroisoquinolinas
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Inibidores Enzimáticos
Limite:
Humans
Idioma:
En
Revista:
ChemMedChem
Ano de publicação:
2018
Tipo de documento:
Article