利用相关方法开发抗癌药物的OTUB1催化位点潜在抑制剂。
Potential Inhibitors of The OTUB1 Catalytic Site to Develop an Anti-Cancer Drug Using Approaches.
作者信息
Galindo-Hernández Octavio, García-Salazar Lizbeth Angelina, García-González Victor Guadalupe, Díaz-Molina Raúl, Vique-Sánchez José Luis
机构信息
Autonomous University of Baja California, School of Medicine Campus Mexicali, Mexicali, BC, México.
出版信息
Rep Biochem Mol Biol. 2023 Jan;11(4):684-693. doi: 10.52547/rbmb.11.4.684.
BACKGROUND
: Cancer continues worldwide. It has been reported that OTUB1, a cysteine protease, plays a critical role in a variety of tumors and is strongly related to tumor proliferation, migration, and clinical prognosis by its functions on deubiquitination. Drug advances continue against new therapeutic targets. In this study we used OTUB1 to develop a specific pharmacological treatment to regulate deubiquitination by OTUB1. The aim of this research is to regulate OTUB1 functions.
METHODS
By molecular docking in a specific potential OTUB1 interaction site between Asp88, Cys91, and His26 amino acids, using a chemical library of over 500,000 compounds, we selected potential inhibitors of the OTUB1 catalytic site.
RESULTS
Ten compounds (OT1 - OT10) were selected by molecular docking to develop a new anti-cancer drug to decrease OTUB1 functions in cancer processes.
CONCLUSION
OT1 - OT10 compounds could be interacting in the potential site between Asp88, Cys91, and His265 amino acids in OTUB1. This site is necessary for the deubiquitinating function of OTUB1. Therefore, this study shows another way to attack cancer.
背景
癌症在全球范围内持续存在。据报道，半胱氨酸蛋白酶OTUB1在多种肿瘤中起关键作用，并且通过其去泛素化功能与肿瘤增殖、迁移及临床预后密切相关。针对新治疗靶点的药物研发不断推进。在本研究中，我们利用OTUB1开发一种特异性药理治疗方法来调节OTUB1介导的去泛素化。本研究的目的是调节OTUB1的功能。
方法
通过在特定的潜在OTUB1相互作用位点（天冬氨酸88、半胱氨酸91和组氨酸26之间）进行分子对接，使用一个包含超过500,000种化合物的化学文库，我们筛选出了OTUB1催化位点的潜在抑制剂。
结果
通过分子对接筛选出10种化合物（OT1 - OT10），用于开发一种新型抗癌药物，以降低OTUB1在癌症进程中的功能。
结论
OT1 - OT10化合物可能在OTUB1中天冬氨酸88、半胱氨酸91和组氨酸265之间的潜在位点相互作用。该位点对于OTUB1的去泛素化功能至关重要。因此，本研究展示了另一种攻克癌症的方法。
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