Neutrophil Elastase-Responsive Linkers for Precision Antibody–Drug Conjugates

IF 3.9 3区医学 Q2 CHEMISTRY, MEDICINAL

ACS Medicinal Chemistry Letters Pub Date : 2026-08-13 Epub Date: 2026-07-14 DOI:10.1021/acsmedchemlett.6c00363

Anna C. Renner, Robert B. Kargbo

引用次数: 0

Abstract

Antibody–drug conjugates (ADCs) continue to transform oncology, yet premature payload release remains a major source of toxicity. This invention describes a novel class of neutrophil elastase-responsive linker systems that incorporate β-homoamino acids, α-methylamino acids, and polyethylene glycol motifs to improve plasma stability while enabling selective drug release at disease sites. These linker technologies offer a versatile platform for enhancing ADC efficacy, safety, and therapeutic precision.

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用于精确抗体-药物偶联物的中性粒细胞弹性酶反应连接物

抗体-药物偶联物（adc）继续改变肿瘤学，但过早的有效载荷释放仍然是毒性的主要来源。本发明描述了一类新的中性粒细胞弹性酶应答连接体系统，其包含β-同型氨基酸、α-甲基氨基酸和聚乙二醇基体，以改善血浆稳定性，同时在疾病部位实现选择性药物释放。这些连接技术为提高ADC的疗效、安全性和治疗精度提供了一个通用的平台。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Medicinal Chemistry Letters CHEMISTRY, MEDICINAL-

CiteScore

7.30

自引率

2.40%

发文量

328

审稿时长

1 months

期刊介绍： ACS Medicinal Chemistry Letters is interested in receiving manuscripts that discuss various aspects of medicinal chemistry. The journal will publish studies that pertain to a broad range of subject matter, including compound design and optimization, biological evaluation, drug delivery, imaging agents, and pharmacology of both small and large bioactive molecules. Specific areas include but are not limited to: Identification, synthesis, and optimization of lead biologically active molecules and drugs (small molecules and biologics) Biological characterization of new molecular entities in the context of drug discovery Computational, cheminformatics, and structural studies for the identification or SAR analysis of bioactive molecules, ligands and their targets, etc. Novel and improved methodologies, including radiation biochemistry, with broad application to medicinal chemistry Discovery technologies for biologically active molecules from both synthetic and natural (plant and other) sources Pharmacokinetic/pharmacodynamic studies that address mechanisms underlying drug disposition and response Pharmacogenetic and pharmacogenomic studies used to enhance drug design and the translation of medicinal chemistry into the clinic Mechanistic drug metabolism and regulation of metabolic enzyme gene expression Chemistry patents relevant to the medicinal chemistry field.