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

  • ACS Med Chem Lett. 2018 Jun 28;9(8):838-842. doi: 10.1021/acsmedchemlett.8b00254.
Alexei S Karpov  1 ,  Tinya Abrams  2 ,  Suzanna Clark  2 ,  Ankita Raikar  2 ,  Joseph A D'Alessio  2 ,  Michael P Dillon  2 ,  Thomas G Gesner  2 ,  Darryl Jones  1 ,  Marion Lacaud  1 ,  William Mallet  3 ,  Piotr Martyniuk  1 ,  Erik Meredith  2 ,  Morvarid Mohseni  2 ,  Cristina M Nieto-Oberhuber  1 ,  Daniel Palacios  2 ,  Francesca Perruccio  1 ,  Grazia Piizzi  1 ,  Mauro Zurini  1 ,  Carl Uli Bialucha  2
Affiliations
  • 1. Novartis Institutes for BioMedical Research, CH-4056 Basel, Switzerland.
  • 2. Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.
  • 3. Novartis Institutes for BioMedical Research, 5300 Chiron Way, Emeryville, California 94608, United States.
PMID: 30128077 DOI: 10.1021/acsmedchemlett.8b00254
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 (ADC-3 and ADC-4) demonstrated in vivo efficacy in the c-Kit positive gastrointestinal stromal tumor GIST-T1 xenograft model in a target-dependent manner.

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