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基于分子对接的糖原合成酶激酶3β筛选分析

Molecular docking based screening analysis of GSK3B.

作者信息

Ogunleye Adewale J, Olanrewaju Afeez J, Arowosegbe Michael, Omotuyi Olaposi I

机构信息

Centre for Biocomputing and Drug Discovery, Adekunle Ajasin University, Nigeria.

BIOTRUST BIOTRUST Scientific, Nigeria, Nigeria.

出版信息

Bioinformation. 2019 Mar 15;15(3):201-208. doi: 10.6026/97320630015201. eCollection 2019.

DOI:10.6026/97320630015201
PMID:31354196
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6637402/
Abstract

GSK3B has been an interesting drug target in the pharmaceutical industry. Its dysfunctional expression has prognostic significance in the top 3 cause of death associated with non-communicable diseases (cancer, Alzheimer's disease and type 2 diabetes). Previous studies have shown clearly that inhibiting GSK3B has proven therapeutic significance in Alzheimer's disease, but its contribution to various cancers has not been clearly resolved. In this study we report the contribution and prognostic significance of GSK3B to two breast cancer subtypes; ductal carcinoma in-situ (DCIS) and invasive ductal carcinoma (IDC) using the Oncomine platform. We performed high throughput screening using molecular docking. We identified BT-000775, a compound that was subjected to further computational hit optimization protocols. Through computational predictions, BT-000775 is a highly selective GSK3B inhibitor, with superior binding affinity and robust ADME profiles suitable for the patho-physiological presentations.

摘要

糖原合成酶激酶3β（GSK3B）一直是制药行业中一个有趣的药物靶点。其功能失调的表达在与非传染性疾病相关的三大死因（癌症、阿尔茨海默病和2型糖尿病）中具有预后意义。先前的研究清楚地表明，抑制GSK3B在阿尔茨海默病中已被证明具有治疗意义，但其对各种癌症的作用尚未明确解决。在本研究中，我们使用Oncomine平台报告了GSK3B对两种乳腺癌亚型；导管原位癌（DCIS）和浸润性导管癌（IDC）的作用及预后意义。我们使用分子对接进行了高通量筛选。我们鉴定出了BT - 000775，一种经过进一步计算命中优化方案的化合物。通过计算预测，BT - 000775是一种高度选择性的GSK3B抑制剂，具有优异的结合亲和力和适合病理生理表现的强大药代动力学性质。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4132/6637402/869d89953b4a/97320630015201F5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4132/6637402/92c9b6d90c23/97320630015201F1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4132/6637402/c42fc426d742/97320630015201F2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4132/6637402/636b28f81b22/97320630015201F3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4132/6637402/4fcd2c075d35/97320630015201F4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4132/6637402/869d89953b4a/97320630015201F5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4132/6637402/92c9b6d90c23/97320630015201F1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4132/6637402/c42fc426d742/97320630015201F2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4132/6637402/636b28f81b22/97320630015201F3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4132/6637402/4fcd2c075d35/97320630015201F4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4132/6637402/869d89953b4a/97320630015201F5.jpg

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