Hydrophobic tagging-induced degradation of NAMPT in leukemia cells  

作　　者：Menglu Guo Ying-Qi Song Junfei Cheng Guoqiang Dong Xun Sun Chunquan Sheng 

机构地区：[1]Department of Natural Medicine,School of Pharmacy,Fudan University,Shanghai 201203,China [2]School of Pharmaceutical Sciences,Hainan University,Haikou 570228,China [3]School of Pharmacy,Second Military Medical University,Shanghai 200433,China

出　　处：《Chinese Chemical Letters》2024年第9期214-218,共5页中国化学快报（英文版）

基　　金：supported by the National Key Research and Development Program of China(No.2022YFC3401500 to C.S.);the National Natural Science Foundation of China(No.82030105 to C.S.);and Shanghai Rising-Star Program(No.20QA1411700 to G.D.)。

摘　　要：Nicotinamide phosphoribosyl transferase(NAMPT)is considered as a promising target for cancer therapy to its crucial role in cancer metabolism.Despite the therapeutic potential of NAMPT enzymatic inhibitors,their effectiveness is limited by dose-related toxicity and the inability to suppress nonenzymatic functions of extracellular NAMPT(e NAMPT).Herein,we designed and synthesized the first hydrophobic tagging NAMPT degraders.Among them,compound NH-11 selectively degraded NAMPT in leukemia cells through the ubiquitin-proteasome system.Compound NH-11 effectively induced apoptosis and showed low toxicity to normal cells,representing a promising anti-leukemia lead compound.?2024 Published by Elsevier B.V.on behalf of Chinese Chemical Society and Institute of Materia Medica,Chinese Academy of Medical Sciences.

关 键 词：NAMPT Hydrophobic tagging LEUKEMIA Degradation ANTI-CANCER 

分 类 号：R965[医药卫生—药理学]