共价药物发现的趋势：2020-23年专利态势分析聚焦于FDA批准药物中的特定共价反应基团（CRGs）
Trends in covalent drug discovery: a 2020-23 patent landscape analysis focused on select covalent reacting groups (CRGs) found in FDA-approved drugs
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影响因子:4.6
分区:医学2区 / 药物化学2区 药学2区
发表日期:2024 Oct
作者:
Jan Felix Scholtes, Cristobal Alhambra, Philip A Carpino
DOI:
10.1080/13543776.2024.2400175
摘要
共价药物包含具有电亲和基团（electrophilic groups），能够与蛋白质活性位点上的核亲氨基酸反应，特别是酶。近年来，利用共价药物靶向蛋白非催化氨基酸以调控难以治疗的靶点（即靶向性共价抑制剂）引起了广泛关注。共价化合物包含多种不同的CRGs，但在已获FDA批准的共价药物中，只有少数CRGs被采用。本文总结了2020-2023年的专利态势分析，重点关注靶点和机构的趋势。分析基于提交至世界知识产权组织（WIPO）的专利申请，通过关键词和结构搜索筛选出在FDA批准药物中出现的CRGs。共计识别出来自300多家机构的707项专利申请，涉及71个靶点。其中五个靶点（BTK、EGFR、FGFR、KRAS、SARS-CoV-2 Mpro）占总申请数的约63%。申请数量最多的机构为学术机构（Dana-Farber癌症研究所）。在KRAS G12C靶点方面，新药的研发竞争尤为激烈，超过100家机构提交了186项专利。
Abstract
Covalent drugs contain electrophilic groups that can react with nucleophilic amino acids located in the active sites of proteins, particularly enzymes. Recently, there has been considerable interest in using covalent drugs to target non-catalytic amino acids in proteins to modulate difficult targets (i.e. targeted covalent inhibitors). Covalent compounds contain a wide variety of covalent reacting groups (CRGs), but only a few of these CRGs are present in FDA-approved covalent drugs.This review summarizes a 2020-23 patent landscape analysis that examined trends in the field of covalent drug discovery around targets and organizations. The analysis focused on patent applications that were submitted to the World International Patent Organization and selected using a combination of keywords and structural searches based on CRGs present in FDA-approved drugs.A total of 707 patent applications from >300 organizations were identified, disclosing compounds that acted at 71 targets. Patent application counts for five targets accounted for ~63% of the total counts (i.e. BTK, EGFR, FGFR, KRAS, and SARS-CoV-2 Mpro). The organization with the largest number of patent counts was an academic institution (Dana-Farber Cancer Institute). For one target, KRAS G12C, the discovery of new drugs was highly competitive (>100 organizations, 186 patent applications).