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一种针对SKP2的小分子抑制剂TAK-491及其应用

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摘要

本发明属于分子靶向治疗领域，具体涉及SKP2蛋白(S‑phase kinase‑associated protein 2)的小分子抑制剂TAK‑491及其在抑制和杀伤胃癌细胞中的应用。一种针对SKP2的小分子抑制剂TAK‑491，该小分子抑制剂TAK‑491的结构式如下：。所述小分子抑制剂可抑制SKP2蛋白进抑制胃癌细胞增殖。所述小分子抑制剂在制备治疗胃癌药物中的应用。本发明提供的SKP2的小分子抑制剂与已知抑制剂相比，亲和力强，可作为一种新的抗肿瘤药物来彻底清除肿瘤和干细胞，具有广泛的应用前景。

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公开/公告号CN113461675A

专利类型发明专利
公开/公告日2021-10-01

原文格式PDF
申请/专利权人中国医科大学附属第一医院;
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申请/专利号CN202010343156.5
发明设计人李凯;
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申请日2020-04-27
分类号C07D413/14(20060101);A61K31/4245(20060101);A61P35/00(20060101);
代理机构21107 沈阳亚泰专利商标代理有限公司;
代理人史力伏
地址 110001 辽宁省沈阳市和平区南京北街155号
入库时间 2023-06-19 12:48:23

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法律状态
2023-04-07

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1. 一种针对SKP2的小分子抑制剂TAK-491及其应用 [P] . 中国专利： CN113461675A . 2021-10-01
2. 一种针对YAP1的小分子抑制剂YAP1-Y7及其应用 [P] . 中国专利： CN113461587A . 2021-10-01
3. Small molecule inhibitors of the E3 Ligase Skp2 in depression and other diseases [P] . 欧洲知识产权局专利： EP2954896A1 . 2015-12-16

机译： E3连接酶Skp2的小分子抑制剂可治疗抑郁症和其他疾病
4. Polinucleotu00eddeo insulated tape of expression, host cell, isolated transgenic non-human animal polypeptide, which has been modified to express a polypeptide mutant with resistance to ALK, antibody that binds specifically to a polypeptide mutant with resistance to ALK, kit p For detection of a mutation with resistance to ALK inhibitor in a biological sample, and,Methods for evaluating a biological sample as a mutation with resistance to ALK inhibitor, for diagnosing a cancer that is resistant to or is likely to develop resistance to at least one inhibitor of kinase small molecule ALK, to evaluate a biological sample that Anto a mutation with resistance to ALK inhibitor.For diagnosing a cancer that is resistant to or is likely to develop resistance to at least one inhibitor of kinase small molecule ALK, to assess the biological sample as a mutation with resistance to ALK inhibitor, a cancer that is resistant to dianosticar Or is likely to develop resistance to PF - 02341066 in a pati [P] . BR112012026239A2 . 2016-11-29

机译：修饰的多聚核苷酸绝缘带，宿主细胞，分离的转基因非人类动物多肽，经过修饰以表达对ALK具有抗性的多肽突变体，与对ALK具有抗性的多肽突变体特异性结合的抗体，试剂盒p用于检测生物样品中对ALK抑制剂具有抗性的突变，以及用于评估生物样品为对ALK抑制剂具有抗性的突变的方法，用于诊断对至少一种对ALK抑制剂具有抗性或可能发展出抗性的癌症激酶小分子ALK，以评估Anto对ALK抑制剂具有抗性的突变的生物样品。用于诊断对至少一种激酶小分子ALK抑制剂具有抗药性或可能产生抗性的癌症，以评估该生物样品作为对ALK抑制剂有抗性的突变，即对狄诺司他抗性或可能对PF产生抗药性的癌症-02341066
5. isolated polynucleotide, expression cassette, host cell, isolated polypeptide, non-human transgenic animal that has been altered to express an alkali resistant mutant polypeptide, an antibody that specifically binds to an alkali resistant mutant polypeptide, a mutation detection kit alk inhibitor resistance in a biological sample, and methods for evaluating a biological sample for an alk inhibitor resistance mutation to diagnose cancer that is resistant to or likely to develop resistance to at least one alkaline inhibitor. small alk molecule kinase, to evaluate a biological sample for an alk inhibitor resistance mutation, to diagnose cancer that is resistant to or likely to develop resistance to pf-02341066 in a patient, to specifically reduce expression of an alk-resistant mutant to treat cancer associated with activating aberrant loop capacity that is resistant to at least one small molecule alk kinase inhibitor treating an aberrant cancer that is resistant to pf-02341066, identifyin [P] . BR112012026239A2 . 2018-06-26

机译：分离的多核苷酸，表达盒，宿主细胞，分离的多肽，已被改变以表达耐碱突变体多肽的非人类转基因动物，与耐碱突变体多肽特异性结合的抗体，突变检测试剂盒生物样品，以及用于评估生物样品中是否存在对烷基抑制剂的抗性突变以诊断对至少一种碱性抑制剂有抗药性或可能发展出抗药性的癌症的方法。小分子激酶，用于评估生物学样品中是否具有抑制碱性磷酸酶抑制剂的突变，以诊断对患者具有抗药性或可能对pf-02341066产生抗药性的癌症，从而特异性降低抗癌突变体的表达以治疗癌症与激活抗至少一种小分子烷基激酶抑制剂的异常环路能力有关，该抑制剂治疗对pf-02341066有抵抗力的异常癌症