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

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 vi...

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Published inACS medicinal chemistry letters Vol. 9; no. 8; pp. 838 - 842
Main Authors Karpov, Alexei S, Abrams, Tinya, Clark, Suzanna, Raikar, Ankita, D’Alessio, Joseph A, Dillon, Michael P, Gesner, Thomas G, Jones, Darryl, Lacaud, Marion, Mallet, William, Martyniuk, Piotr, Meredith, Erik, Mohseni, Morvarid, Nieto-Oberhuber, Cristina M, Palacios, Daniel, Perruccio, Francesca, Piizzi, Grazia, Zurini, Mauro, Bialucha, Carl Uli
Format Journal Article
LanguageEnglish
Published WASHINGTON American Chemical Society 09.08.2018
Amer Chemical Soc
Subjects
Chemistry, Medicinal
Letter
Life Sciences & Biomedicine
Pharmacology & Pharmacy
Science & Technology
Antibody−drug conjugate (ADC)
novel payload
nicotinamide phosphoribosyltransferase (NAMPT)
DESIGN
EFFICACY
HER2-TARGETING ADC
T-DM1
Antibody-drug conjugate (ADC)
CANCER
DISCOVERY
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ISSN1948-5875
1948-5875
DOI10.1021/acsmedchemlett.8b00254

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Summary: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.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:1948-5875
1948-5875
DOI:10.1021/acsmedchemlett.8b00254