title: BCR-ABL tyrosine kinase inhibitor pharmacophore model derived from a series of phenylaminopyrimidine-based (PAP) derivatives.
abstract: To reveal novel insights into the inhibition of BCR-ABL tyrosine kinase, pharmacophore mapping studies were performed for a series of phenylaminopyrimidine-based (PAP) derivatives, including imatinib (Gleevec). A seven-point pharmacophore model with one hydrophobic group (H), two hydrogen bond donors (D) and four aromatic rings (R) was developed using phase (pharmacophore alignment & scoring engine). The pharmacophore hypothesis yielded a statistically significant 3D-QSAR model, with a correlation coefficient of 0.886 and a survival score of 4.97 for training set molecules. The model showed excellent predictive power, with a correlation coefficient of Q(2)=0.768 for an external test set of ten molecules. The results obtained from our studies provide a valuable tool for designing new lead molecules with potent activity.
authors.affiliation: Department of Hematology, The First People's Hospital of Hangzhou, No 261 Huansha Road, Hangzhou 310006, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Cui
authors.forename: Rao
authors.initials: R
authors.lastname: Fu
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Zhou
authors.forename: Sheng-Ping
authors.initials: SP
authors.lastname: Chen
authors.forename: Guang-Wu
authors.initials: GW
authors.lastname: Li
authors.forename: Shen-Xian
authors.initials: SX
authors.lastname: Qian
authors.forename: Shu
authors.initials: S
authors.lastname: Liu
mesh_terms: D015195:Drug Design; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D011743:Pyrimidines / Q000737:chemistry* / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship
chemical_list: D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D016044:Fusion Proteins, bcr-abl