Discovery of 2-(5-(quinolin-6-yl)-1,3,4-oxadiazol-2-yl)acetamide derivatives as novel PI3Kα inhibitors via docking-based virtual screening. 2021

Dongyan Gu, and Gang Cheng, and Mengmeng Zhang, and Yu-Bo Zhou, and Jia Li, and Rong Sheng
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, PR China.

PI3Kα is an attractive target for PIK3CA mutated malignant tumor and searching for lead compounds with novel scaffold is important for the development of PI3Kα inhibitors. Therefore, the strategy of docking-based virtual screening was performed to discovery potent inhibitors. The 4L2Y_A PI3Kα crystal structure was used as the model protein receptor due to its high docking reliability. After the multistep virtual screening protocol and biological evaluation, three hits were picked up and further similarity searching led to more potent 2-(5-(quinolin-6-yl)-1,3,4-oxadiazol-2-yl)acetamide derivatives ES-25 and ES-27. In addition, the primary SAR of these novel derivatives was discussed, which provide a basis for the further structural modification.

UI MeSH Term Description Entries
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004353 Drug Evaluation, Preclinical Preclinical testing of drugs in experimental animals or in vitro for their biological and toxic effects and potential clinical applications. Drug Screening,Evaluation Studies, Drug, Pre-Clinical,Drug Evaluation Studies, Preclinical,Drug Evaluations, Preclinical,Evaluation Studies, Drug, Preclinical,Evaluation, Preclinical Drug,Evaluations, Preclinical Drug,Medicinal Plants Testing, Preclinical,Preclinical Drug Evaluation,Preclinical Drug Evaluations,Drug Screenings,Screening, Drug,Screenings, Drug
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000081 Acetamides Derivatives of acetamide that are used as solvents, as mild irritants, and in organic synthesis.
D000081082 Phosphoinositide-3 Kinase Inhibitors Agents that inhibit PHOSPHOINOSITIDE-3 KINASE activity. Phosphoinositide-3 Kinase Inhibitor,Inhibitor, Phosphoinositide-3 Kinase,Inhibitors, Phosphoinositide-3 Kinase,Kinase Inhibitor, Phosphoinositide-3,Kinase Inhibitors, Phosphoinositide-3,Phosphoinositide 3 Kinase Inhibitor,Phosphoinositide 3 Kinase Inhibitors
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D015394 Molecular Structure The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. Structure, Molecular,Molecular Structures,Structures, Molecular
D055808 Drug Discovery The process of finding chemicals for potential therapeutic use. Drug Prospecting,Discovery, Drug,Prospecting, Drug
D058534 Class I Phosphatidylinositol 3-Kinases A phosphatidylinositol 3-kinase subclass that includes enzymes with a specificity for 1-phosphatidylinositol, 1-phosphatidylinositol 4-phosphate, and 1-phosphatidylinositol 4,5-bisphosphate. Members of this enzyme subclass are activated by cell surface receptors and occur as heterodimers of enzymatic and regulatory subunits. Phosphatidylinositol 3-Kinase, Class I,Class I Phosphatidylinositol 3-Kinase,Class I Phosphatidylinositol 3 Kinase,Class I Phosphatidylinositol 3 Kinases,Phosphatidylinositol 3 Kinase, Class I
D062105 Molecular Docking Simulation A computer simulation technique that is used to model the interaction between two molecules. Typically the docking simulation measures the interactions of a small molecule or ligand with a part of a larger molecule such as a protein. Molecular Docking,Molecular Docking Simulations,Molecular Docking Analysis,Analysis, Molecular Docking,Docking Analysis, Molecular,Docking Simulation, Molecular,Docking, Molecular,Molecular Docking Analyses,Molecular Dockings,Simulation, Molecular Docking

Related Publications

Dongyan Gu, and Gang Cheng, and Mengmeng Zhang, and Yu-Bo Zhou, and Jia Li, and Rong Sheng
October 2008, Bioorganic & medicinal chemistry letters,
Dongyan Gu, and Gang Cheng, and Mengmeng Zhang, and Yu-Bo Zhou, and Jia Li, and Rong Sheng
June 2021, International journal of molecular sciences,
Dongyan Gu, and Gang Cheng, and Mengmeng Zhang, and Yu-Bo Zhou, and Jia Li, and Rong Sheng
May 2023, Bioorganic & medicinal chemistry,
Dongyan Gu, and Gang Cheng, and Mengmeng Zhang, and Yu-Bo Zhou, and Jia Li, and Rong Sheng
June 2021, Bioorganic & medicinal chemistry letters,
Dongyan Gu, and Gang Cheng, and Mengmeng Zhang, and Yu-Bo Zhou, and Jia Li, and Rong Sheng
October 2016, Bioorganic & medicinal chemistry letters,
Dongyan Gu, and Gang Cheng, and Mengmeng Zhang, and Yu-Bo Zhou, and Jia Li, and Rong Sheng
November 2019, Acta crystallographica. Section C, Structural chemistry,
Dongyan Gu, and Gang Cheng, and Mengmeng Zhang, and Yu-Bo Zhou, and Jia Li, and Rong Sheng
August 2019, Drug development research,
Dongyan Gu, and Gang Cheng, and Mengmeng Zhang, and Yu-Bo Zhou, and Jia Li, and Rong Sheng
May 2019, Bioorganic chemistry,
Dongyan Gu, and Gang Cheng, and Mengmeng Zhang, and Yu-Bo Zhou, and Jia Li, and Rong Sheng
July 2008, Acta crystallographica. Section E, Structure reports online,
Dongyan Gu, and Gang Cheng, and Mengmeng Zhang, and Yu-Bo Zhou, and Jia Li, and Rong Sheng
November 2013, Archiv der Pharmazie,
Copied contents to your clipboard!