title: Targeting Pim-1 kinase for potential drug-development.
abstract: Dysregulation of Pim-1 kinase has been implicated in several human cancers. Many potential inhibitors of PIM kinase have been reported, but potential bioactive compounds are still far from reach. Keeping this in mind, we have selected structurally known diverse Pim-1 kinase inhibitors to find novel small molecule drug-leads. A ligand-based pharmacophore model for Pim-1 kinase was developed using PHASE software. A four feature pharmacophoric hypothesis (AAHR) was used to develop atom-based 3D-QSAR model with the best regression coefficient of 0.9433 and Pearson-R of 0.9344. Compounds from Asinex platinum database were obtained whose pIC(50) values matched the 3D-QSAR model. Structural and molecular interaction studies on the training and test sets suggest that designing novel compounds hydrogen bond with Asp128 in the bioactive region of Pim-1 kinase would result in therapeutic success.
authors.affiliation: Bioinformatics Center, Advanced Center for Treatment, Research and Education in Cancer, Kharghar, Navi Mumbai, India. ngadewal@actrec.gov.in
authors.forename: Nikhil
authors.initials: N
authors.lastname: Gadewal
authors.forename: Ashok
authors.initials: A
authors.lastname: Varma
mesh_terms: D015195:Drug Design; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D051573:Proto-Oncogene Proteins c-pim-1 / Q000037:antagonists & inhibitors; D021281:Quantitative Structure-Activity Relationship
chemical_list: D047428:Protein Kinase Inhibitors; D051573:Proto-Oncogene Proteins c-pim-1