共价药物发现的趋势：2020 - 23年的专利景观分析，重点是在FDA批准的药物中发现的共价反应组（CRG）
Trends in covalent drug discovery: a 2020-23 patent landscape analysis focused on select covalent reacting groups (CRGs) found in FDA-approved drugs
影响因子:4.60000
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
摘要
共价药物含有可与位于蛋白质活性部位（尤其是酶的活性部位）反应的亲电基团。最近，人们对使用共价药物靶向蛋白质中的非催化氨基酸来调节困难靶标（即靶向共价抑制剂）。共价化合物含有各种共价反应基（CRG），但是在FDA批准的共价药物中只存在其中一些CRG。这本综述总结了2020 - 23年的专利景观分析，研究了目标和组织周围共计药物发现领域的趋势。该分析的重点是提交给世界国际专利组织的专利申请，并根据基于FDA批准的药物中存在的CRG进行了使用关键字和结构搜索的组合。总共确定了> 300个组织的707个专利申请，披露了71个目标的披露化合物。五个目标的专利申请计数约占总数的63％（即BTK，EGFR，FGFR，KRAS，KRAS和SARS-COV-2 MPRO）。专利数量数量最多的组织是一家学术机构（Dana-Farber Cancer Institute）。对于一个目标是KRAS G12C，新药的发现具有很高的竞争力（> 100个组织，186种专利申请）。
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).