Potential virtual lead identification in the discovery of renin inhibitors: application of ligand and structure-based pharmacophore modeling approaches.
Article Details
- CitationCopy to clipboard
Thangapandian S, John S, Sakkiah S, Lee KW
Potential virtual lead identification in the discovery of renin inhibitors: application of ligand and structure-based pharmacophore modeling approaches.
Eur J Med Chem. 2011 Jun;46(6):2469-76. doi: 10.1016/j.ejmech.2011.03.035. Epub 2011 Mar 25.
- PubMed ID
- 21497958 [ View in PubMed]
- Abstract
Renin, an enzyme by cleaving angiotensinogen to angiotensin-I, controls the first and rate-limiting step of renin-angiotensin system that is associated with blood pressure. Thus Ligand and structure-based pharmacophore models were developed in this study to identify new potential leads inhibiting this rate-limiting enzyme as an efficient way to treat blood pressure. X-ray predicted binding modes of most active compounds were used in ligand-based approach whereas the 3D structural information of renin was used in structure-based approach. Pharmacophore models were validated using various methods and utilized in database searching to identify potential hits. Drug-like filters and molecular docking studies led us identifying the final hits to be employed in designing new class of future renin inhibitors.