Structural Basis for Resistance to Diverse Classes of NAMPT Inhibitors

  title={Structural Basis for Resistance to Diverse Classes of NAMPT Inhibitors},
  author={Weiru Wang and Kristi Elkins and Angela Jinsook Oh and Yen-Ching Ho and Jiansheng Wu and Hong Li and Yang Xiao and Mandy Kwong and Mary Patricia Coons and Bobby Brillantes and Eric Cheng and Lisa M Crocker and Peter S Dragovich and Deepak Sampath and Xiaozhang Zheng and Kenneth W. Bair and Thomas O'Brien and Lisa D. Belmont and Wenqing Xu},
  booktitle={PloS one},
Inhibiting NAD biosynthesis by blocking the function of nicotinamide phosphoribosyl transferase (NAMPT) is an attractive therapeutic strategy for targeting tumor metabolism. However, the development of drug resistance commonly limits the efficacy of cancer therapeutics. This study identifies mutations in NAMPT that confer resistance to a novel NAMPT inhibitor, GNE-618, in cell culture and in vivo, thus demonstrating that the cytotoxicity of GNE-618 is on target. We determine the crystal… CONTINUE READING