AI Article Synopsis
- Matrix metalloproteinase 13 (MMP-13) is crucial in osteoarthritis (OA) as it causes collagen breakdown, disrupting the balance between collagen production and degradation, which leads to cartilage damage.
- Researchers have created a virtual screening process to find specific non-zinc-binding inhibitors for MMP-13 by focusing on its S1' pocket.
- They identified three ligands that inhibit MMP-13 effectively, with one showing selectivity over other MMPs, and further refined this to develop a new compound with enhanced inhibitory effectiveness and selectivity.
Article Abstract
Matrix metalloproteinase 13 plays a central role in osteoarthritis (OA), as its overexpression induces an excessive breakdown of collagen that results in an imbalance between collagen synthesis and degradation in the joint, leading to progressive articular cartilage degradation. Therefore, MMP-13 has been proposed as a key therapeutic target for OA. Here we have developed a virtual screening workflow aimed at identifying selective non-zinc-binding MMP-13 inhibitors by targeting the deep S1' pocket of MMP-13. Three ligands were found to inhibit MMP-13 in the µM range, and one of these showed selectivity over other MMPs. A structure-based analysis guided the chemical optimization of the hit compound, leading to the obtaining of a new -acyl hydrazone-based derivative with improved inhibitory activity and selectivity for the target enzyme.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10342305 | PMC |
| http://dx.doi.org/10.3390/ijms241311098 | DOI Listing |
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Article Synopsis
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- Researchers have created a virtual screening process to find specific non-zinc-binding inhibitors for MMP-13 by focusing on its S1' pocket.
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