Authors: Nikhil Gadewal; Ashok Varma
Addresses: Bioinformatics Center, Advanced Center for Treatment, Research and Education in Cancer (ACTREC), Kharghar, Navi Mumbai, India ' Bioinformatics Center, Advanced Center for Treatment, Research and Education in Cancer (ACTREC), Kharghar, Navi Mumbai, India
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 pIC50 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.
Keywords: Pim-1 kinase; 3D-QSAR; kinase inhibitors; anti-cancer inhibitors; pharmacophore models; cancer drugs; structural interaction; molecular interaction; drug development.
International Journal of Computational Biology and Drug Design, 2012 Vol.5 No.2, pp.137 - 151
Received: 10 Jan 2012
Accepted: 06 Apr 2012
Published online: 30 Jul 2012 *