Discovery of potent NAMPT-Targeting PROTACs using FK866 as the warhead.
Bioorg Med Chem Lett
; 92: 129393, 2023 08 15.
Article
en En
| MEDLINE
| ID: mdl-37369332
ABSTRACT
Nicotinamide phosphoribosyltransferase (NAMPT) has emerged as a promising target for cancer therapy due to its strong correlation with nicotinamide adenine dinucleotide (NAD+) metabolism and tumorigenesis. Proteolysis targeting chimeras (PROTACs) provided an attractive strategy for developing NAMPT-targeting NAD+-depleting cancer drugs. Herein, a series of von Hippel-Lindau (VHL)-recruiting NAMPT-targeting PROTACs were designed using NAMPT inhibitor FK866 as the warhead. Among them, compound C5 degraded NAMPT (DC50 = 31.7 nM) in a VHL- and proteasome-dependent manner. Moreover, compound C5 effectively inhibited the proliferation of A2780 cells (IC50 = 30.6 nM) and significantly reduced the general cytotoxicity of FK866 to normal cells.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias Ováricas
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Nicotinamida Fosforribosiltransferasa
/
Quimera Dirigida a la Proteólisis
Límite:
Female
/
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2023
Tipo del documento:
Article
País de afiliación:
China