Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/38769
Title: IDENTIFICATION OF DRUG-LIKE MOLECULES AGAINST MATRIX METALLO PROTEINASE-13 HEMOPEXIN DOMAIN
Authors: ROOPA KOTHAPALLI
Keywords: MMP, MMP-13, hemopexin domain, breast cancer, arthritis, structure based drug design and x-ray crystallography,
Issue Date: 2-Jan-2013
Source: ROOPA KOTHAPALLI (2013-01-02). IDENTIFICATION OF DRUG-LIKE MOLECULES AGAINST MATRIX METALLO PROTEINASE-13 HEMOPEXIN DOMAIN. ScholarBank@NUS Repository.
Abstract: Matrix metalloproteinase-13 (MMP-13) has long been considered as a target for the inhibition of the progression of osteoarthritis (OA), rheumatoid arthritis (RA) and cancer. It catalyzes the cleavage of type II collagen (the main structural component of the articular cartilage). This protein is usually expressed in OA and RA patients, and recently found in breast cancer, but not in normal adults. Therefore, this protease is an important target for the inhibition of progression of OA, RA and cancer. We applied in silico structure-based high-throughput virtual screening (HTVS) and identified 7 ligands from the Maybridge, PubChem and Binding libraries which uniquely interact with the putative functional residues of the MMP-13 Hpx domain. Our recent cell based experimental results suggest that selective inhibition of MMP-13 may be achieved by targeting its hemopexin (Hpx) domain, which is critical for substrate specificity. We further experimentally validated these potential and selective MMP-13 inhibitors using in vitro and X-ray crystallographic studies. These seven molecules and their backbone scaffold could serve as building blocks in designing drug-like molecules for OA, RA and cancer.
URI: http://scholarbank.nus.edu.sg/handle/10635/38769
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