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Published on: January 22, 2019
Targeting Pim-1 kinase for potential drug-development
1Bioinformatics Center, Advanced Center for Treatment, Research and Education in Cancer, Kharghar, Navi Mumbai, India. ngadewal@actrec.gov.in
Summary
Researchers identified novel small molecule drug leads for Pim-1 kinase, a target implicated in human cancers. Designing compounds that hydrogen bond with Asp128 in Pim-1 kinase shows therapeutic promise.
Area of Science:
- Medicinal Chemistry
- Computational Drug Discovery
- Oncology
Background:
- Dysregulation of Pim-1 kinase is linked to various human cancers.
- Developing effective Pim-1 kinase inhibitors remains a significant challenge in drug discovery.
Purpose of the Study:
- To identify novel small molecule drug leads for Pim-1 kinase.
- To develop a predictive model for identifying potential Pim-1 kinase inhibitors.
Main Methods:
- A ligand-based pharmacophore model for Pim-1 kinase was constructed using PHASE software.
- An atom-based 3D-QSAR model (AAHR hypothesis) was developed, achieving a regression coefficient of 0.9433.
- Compounds from the Asinex Platinum database were screened against the 3D-QSAR model.
Main Results:
- The 3D-QSAR model demonstrated high predictive accuracy.
- Selected compounds from the Asinex Platinum database showed promising pIC(50) values.
- Structural and molecular interaction studies highlighted the importance of hydrogen bonding with Asp128.
Conclusions:
- Novel drug leads for Pim-1 kinase were identified through pharmacophore modeling and 3D-QSAR.
- Designing compounds that form hydrogen bonds with Asp128 is a promising strategy for therapeutic success against Pim-1 kinase-related cancers.
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