{"title":"Computational Design of Phosphatidylinositol 3-Kinase Inhibitors.","authors":"Isha Rani, Anju Goyal, M Sharma","doi":"10.1089/adt.2022.057","DOIUrl":null,"url":null,"abstract":"<p><p>\n <i>One of the most sought-after therapeutic targets for treating human cancers is the phosphoinositide 3-kinase; PI3k is an integral part of the PI3K/protein kinase B signaling arcade. This pathway is frequently activated in malignancies. Drug resistance and dose-limiting adverse effects are currently associated challenges with the existing anticancer chemotherapy. Therefore, in this research, a series of pyrimidine derivatives were designed and evaluated against human PI3K by using molecular docking analysis. The docking results were further verified by molecular dynamic simulation, which analyzed the strength of the macromolecular complex with respect to time. Compounds IV and XIV were found to be the most potent inhibitors of the human PI3K receptor with a high degree of stability within the active site of the target receptor for a timeframe of 50 ns. Thus, both of these compounds could be important drug candidates for the development of PI3K inhibitors as a prospective anticancer agent.</i>\n </p>","PeriodicalId":8586,"journal":{"name":"Assay and drug development technologies","volume":"20 7","pages":"317-337"},"PeriodicalIF":1.6000,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"5","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Assay and drug development technologies","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1089/adt.2022.057","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
引用次数: 5
Abstract
One of the most sought-after therapeutic targets for treating human cancers is the phosphoinositide 3-kinase; PI3k is an integral part of the PI3K/protein kinase B signaling arcade. This pathway is frequently activated in malignancies. Drug resistance and dose-limiting adverse effects are currently associated challenges with the existing anticancer chemotherapy. Therefore, in this research, a series of pyrimidine derivatives were designed and evaluated against human PI3K by using molecular docking analysis. The docking results were further verified by molecular dynamic simulation, which analyzed the strength of the macromolecular complex with respect to time. Compounds IV and XIV were found to be the most potent inhibitors of the human PI3K receptor with a high degree of stability within the active site of the target receptor for a timeframe of 50 ns. Thus, both of these compounds could be important drug candidates for the development of PI3K inhibitors as a prospective anticancer agent.
期刊介绍：
ASSAY and Drug Development Technologies provides access to novel techniques and robust tools that enable critical advances in early-stage screening. This research published in the Journal leads to important therapeutics and platforms for drug discovery and development. This reputable peer-reviewed journal features original papers application-oriented technology reviews, topical issues on novel and burgeoning areas of research, and reports in methodology and technology application.
ASSAY and Drug Development Technologies coverage includes:
-Assay design, target development, and high-throughput technologies-
Hit to Lead optimization and medicinal chemistry through preclinical candidate selection-
Lab automation, sample management, bioinformatics, data mining, virtual screening, and data analysis-
Approaches to assays configured for gene families, inherited, and infectious diseases-
Assays and strategies for adapting model organisms to drug discovery-
The use of stem cells as models of disease-
Translation of phenotypic outputs to target identification-
Exploration and mechanistic studies of the technical basis for assay and screening artifacts
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
