Your browser doesn't support javascript.
loading
Ispinesib as an Effective Warhead for the Design of Autophagosome-Tethering Chimeras: Discovery of Potent Degraders of Nicotinamide Phosphoribosyltransferase (NAMPT).
Dong, Guoqiang; Wu, Ying; Cheng, Junfei; Chen, Long; Liu, Rui; Ding, Yu; Wu, Shanchao; Ma, Junhui; Sheng, Chunquan.
  • Dong G; School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
  • Wu Y; School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
  • Cheng J; Department of Pharmacy, 920th Hospital of Joint Logistics Support Force, Kunming 650032, China.
  • Chen L; School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
  • Liu R; School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
  • Ding Y; School of Life Sciences, Fudan University, 220 Handan Road, Shanghai 200433, China.
  • Wu S; School of Life Sciences, Fudan University, 220 Handan Road, Shanghai 200433, China.
  • Ma J; School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
  • Sheng C; School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China.
J Med Chem ; 65(11): 7619-7628, 2022 06 09.
Article en En | MEDLINE | ID: mdl-35588495
Autophagosome-tethering compounds (ATTECs) are an emerging new technology in targeted protein degradation. However, effective tools and successful examples for autophagosome-tethering chimeras are still rather limited. Herein, ATTEC ispinesib was identified for the first time to be an effective warhead to design autophagosome-tethering chimeras. As a conceptual validation study, the first generation of autophagic degraders of nicotinamide phosphoribosyltransferase (NAMPT) were developed by connecting the NAMPT inhibitor and LC3-binding ispinesib through a flexible linker. In particular, compound A3 significantly induced the degradation of NAMPT through the autophagy-lysosomal pathway, leading to excellent cellular antitumor potency. Ispinesib may have broad applications in the design of potent autophagosome-tethering chimeras.
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Nicotinamida Fosforribosiltransferasa / Autofagosomas Tipo de estudio: Prognostic_studies Idioma: En Año: 2022 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Nicotinamida Fosforribosiltransferasa / Autofagosomas Tipo de estudio: Prognostic_studies Idioma: En Año: 2022 Tipo del documento: Article