UNASSIGNED: This review covers patent literature disclosed during the 2019-30 June 2023 period which claim ATPase inhibitors and PROTAC degraders that bind to the ATPase domain of SMARCA2 and/or SMARCA4. A total of 16 documents from 6 applicants are presented.
UNASSIGNED: The demonstration of cellular dependence on SMARCA2 ATPase activity in SMARCA4-deficient settings has prompted substantial research toward SMARCA2-targeting therapies. Although selectively targeting the ATPase domain of SMARCA2 is viewed as challenging, several ATPase inhibitor scaffolds have been disclosed within the last five years. Most early compounds are weakly selective, but these efforts have culminated in the first dual SMARCA2/SMARCA4 ATPase inhibitor to enter clinical trials. Data from the ongoing clinical trials, as well as continued advancement of SMARCA2-selective ATPase inhibitors, are anticipated to significantly impact the field of therapies, targeting SMARCA4-deficient tumors.
■本综述涵盖了在2019-2023年6月30日期间公开的专利文献,该专利文献要求与SMARCA2和/或SMARCA4的ATPase结构域结合的ATPase抑制剂和PROTAC降解物。共提交了来自6名申请人的16份文件。
■在缺乏SMARCA4的环境中,细胞对SMARCA2ATPase活性的依赖性的证明促使对SMARCA2靶向疗法的大量研究。尽管选择性靶向SMARCA2的ATPase结构域被认为具有挑战性,在过去的五年中,已经公开了几种ATP酶抑制剂支架。大多数早期化合物的选择性较弱,但这些努力最终导致首个双重SMARCA2/SMARCA4ATP酶抑制剂进入临床试验.来自正在进行的临床试验的数据,以及SMARCA2选择性ATP酶抑制剂的持续发展,预计将对治疗领域产生重大影响,靶向SMARCA4缺陷型肿瘤。