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

[Image: see text] 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)...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2018
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6088352/
https://www.ncbi.nlm.nih.gov/pubmed/30128077
http://dx.doi.org/10.1021/acsmedchemlett.8b00254
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author 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
author_facet 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
author_sort Karpov, Alexei S.
collection PubMed
description [Image: see text] 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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spelling pubmed-60883522018-08-20 Nicotinamide Phosphoribosyltransferase Inhibitor as a Novel Payload for Antibody–Drug Conjugates 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 ACS Med Chem Lett [Image: see text] 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. American Chemical Society 2018-06-28 /pmc/articles/PMC6088352/ /pubmed/30128077 http://dx.doi.org/10.1021/acsmedchemlett.8b00254 Text en Copyright © 2018 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle 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
Nicotinamide Phosphoribosyltransferase Inhibitor as a Novel Payload for Antibody–Drug Conjugates
title Nicotinamide Phosphoribosyltransferase Inhibitor as a Novel Payload for Antibody–Drug Conjugates
title_full Nicotinamide Phosphoribosyltransferase Inhibitor as a Novel Payload for Antibody–Drug Conjugates
title_fullStr Nicotinamide Phosphoribosyltransferase Inhibitor as a Novel Payload for Antibody–Drug Conjugates
title_full_unstemmed Nicotinamide Phosphoribosyltransferase Inhibitor as a Novel Payload for Antibody–Drug Conjugates
title_short Nicotinamide Phosphoribosyltransferase Inhibitor as a Novel Payload for Antibody–Drug Conjugates
title_sort nicotinamide phosphoribosyltransferase inhibitor as a novel payload for antibody–drug conjugates
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6088352/
https://www.ncbi.nlm.nih.gov/pubmed/30128077
http://dx.doi.org/10.1021/acsmedchemlett.8b00254
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