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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 (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.

SUBMITTER: Karpov AS

PROVIDER: S-EPMC6088352 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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

Karpov Alexei S AS Abrams Tinya T Clark Suzanna S Raikar Ankita A D'Alessio Joseph A JA Dillon Michael P MP Gesner Thomas G TG Jones Darryl D Lacaud Marion M Mallet William W Martyniuk Piotr P Meredith Erik E Mohseni Morvarid M Nieto-Oberhuber Cristina M CM Palacios Daniel D Perruccio Francesca F Piizzi Grazia G Zurini Mauro M Bialucha Carl Uli CU

ACS medicinal chemistry letters 20180628 8

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. ...[more]

PMID: 30128077

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