Nicotinamide Phosphoribosyltransferase Inhibitor as a Novel Payload for Antibody–Drug Conjugates

Abstract

Antibody-drug conjugates (ADCs) are a novel modality that allows targeted delivery of potent therapeutic agents to the desired site. Herein we report our discovery of NAMPT inhibitors as a novel nonantimitotic payload for ADCs. The resulting anti-c-Kit conjugates (<b>ADC-3</b> and <b>ADC-4</b>) demonstrated <i>in vivo</i> efficacy in the c-Kit positive gastrointestinal stromal tumor GIST-T1 xenograft model in a target-dependent manner.