title: QSAR models for isoindolinone-based p53-MDM2 interaction inhibitors using linear and non-linear statistical methods.
abstract: The design and optimization of p53-MDM2 interaction inhibitors has attracted a great deal of interest in the development of new anticancer agents. Systematical 2D-QSAR studies on 98 isoindolinone-based p53-MDM2 interaction inhibitors were carried out using linear and the non-linear mathematical methods. At first, a forward stepwise-multiple linear regression model (FS-MLR) was proposed with reasonable statistical parameters (R(2)(train) =0.881, Q(2)(loo) =0.847, R(2)(test) =0.854). Then, enhanced replacement method-multiple linear regression (ERM-MLR) and support vector machine regression (SVMR) were applied to set up more accurate models (ERM-MLR: R(2)(train) =0.914, Q(2)(loo) =0.894 and R(2)(test) =0.903; SVMR: R(2)(train) =0.924, Q(2)(loo) =0.920 and R(test) (2) of 0.874). Furthermore, the reliability and application value of the ERM and SVMR model was also validated in virtual screening through receiver operating characteristic studies.
authors.affiliation: ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
authors.forename: Xiaowu
authors.initials: X
authors.lastname: Dong
authors.forename: Jingying
authors.initials: J
authors.lastname: Yan
authors.forename: Dong
authors.initials: D
authors.lastname: Lu
authors.forename: Peng
authors.initials: P
authors.lastname: Wu
authors.forename: Jiadi
authors.initials: J
authors.lastname: Gao
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Yongzhou
authors.initials: Y
authors.lastname: Hu
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D054833:Isoindoles / Q000737:chemistry* / Q000494:pharmacology; D016014:Linear Models; D015233:Models, Statistical; D009369:Neoplasms / Q000188:drug therapy; D025941:Protein Interaction Mapping; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D021281:Quantitative Structure-Activity Relationship; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D054833:Isoindoles; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2