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烟酰胺磷酸核糖基转移酶抑制剂作为抗体药物偶联物的新型有效载荷

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

作者信息

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

机构信息

Novartis Institutes for BioMedical Research, CH-4056 Basel, Switzerland.

Novartis Institutes for BioMedical Research, 250 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.

出版信息

ACS Med Chem Lett. 2018 Jun 28;9(8):838-842. doi: 10.1021/acsmedchemlett.8b00254. eCollection 2018 Aug 9.

DOI:10.1021/acsmedchemlett.8b00254
PMID:30128077
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6088352/
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 ( and ) demonstrated efficacy in the c-Kit positive gastrointestinal stromal tumor GIST-T1 xenograft model in a target-dependent manner.

摘要

抗体药物偶联物（ADCs）是一种新型药物，可将强效治疗剂靶向递送至所需部位。在此，我们报告发现烟酰胺磷酸核糖转移酶（NAMPT）抑制剂作为ADCs的一种新型非抗有丝分裂有效载荷。由此产生的抗c-Kit偶联物（和）在c-Kit阳性胃肠道间质瘤GIST-T1异种移植模型中以靶点依赖的方式显示出疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a0f/6088352/60d0037211e1/ml-2018-00254q_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a0f/6088352/6282c1342d19/ml-2018-00254q_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a0f/6088352/ae873ab18410/ml-2018-00254q_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a0f/6088352/b927cc121132/ml-2018-00254q_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a0f/6088352/69d34c01dca3/ml-2018-00254q_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a0f/6088352/60d0037211e1/ml-2018-00254q_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a0f/6088352/6282c1342d19/ml-2018-00254q_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a0f/6088352/ae873ab18410/ml-2018-00254q_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a0f/6088352/b927cc121132/ml-2018-00254q_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a0f/6088352/69d34c01dca3/ml-2018-00254q_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a0f/6088352/60d0037211e1/ml-2018-00254q_0005.jpg

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