Matrix metalloproteinases (MMPs) are a class of zinc-dependent endopeptidases belonging to the mecenin superfamily of metalloproteinases that collectively have the ability to degrade every component of the extracellular matrix (ECM), and are characterized by the presence of a catalytic zinc atom in their active center. To date, scientists have identified at least 25 different vertebrate MMPs, 24 of which are present in humans: collagenases, gelatinases, MT-MMPs, matrix lysins, matrices, and other types. MMPs have long been used as promising targets for treatment of various pathologies, including cancer (tumor angiogenesis and metastasis), osteoarthritis (OA), inflammation, periodontitis, vascular disease, post-myocardial infarction remodeling, neurodegenerative diseases and neuropsychiatric disorders. Due to the important role of MMPs in cancer, a variety of MMPIs have been investigated, and the development of MMP inhibitors typically follows the path of inhibition at the active site of Zn2+.
To meet the growing demand for new structures for drug discovery projects, BOC Sciences has designed its dedicated matrix metalloproteinase focused library to generate small-molecule analogs of known ligase inhibitors with high bioactivity for the application in high-throughput screening (HTS) and high-content screening (HCS) programs.
Figure 1. Structural alignment of MMP-9CAT and MMP-14CAT in complex with N-TIMP2. (Shirian, J.; et al. 2018)
Library Design
BOC Sciences has designed its screening library of potential matrix metalloproteinase inhibitors based on a rigid selection by structural and physicochemical parameters.
- Firstly, our scientists apply a series of reliable databases to obtain a reference set of 30,000 compounds with known MMPs blocking activity
- These compounds have been pre-filtered to retain only those with moderate and high activity against ligase targets, leaving only those with moderate and high activity against MMPs that narrowed down a set to 7,000 compounds
- In this step, a similarity search of the reference set is performed against the BOC Sciences HTS compound collection using 2D molecular fingerprinting and two similarity metrics
The matrix metalloproteinase focused library contains more than 2,000 screening compounds with predicted activity against the following targets.
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Figure 2. A pairwise alignment of residues on MMP-1CAT, MMP-2CAT, MMP-9CAT, MMP-10CAT, and MMP-14CAT. (Shirian, J.; et al. 2018)
Matrix Metalloproteinase Focused Library Characteristics
- No PAINS or toxic substances/unwanted functions: filtered by strict ‘Ro5-like’ physicochemical and most stringent in-house structural filters
- All PAIN and reactive compounds are excluded from selection by internal filter applications
- IC50, Ki ,etc less than 10 μM, inhibition >25%
- Confirmed bioactivity and safety via preclinical studies and clinical trials
- All of the compounds have been selected by ligand efficacy and predicted binding mode
- Structural diversity, significant efficacy, and cellular penetration
- Structural document, IC50, and other chemical and biological data are provided
- Tanimoto index ≥ 0.75
- All compounds are continually updated
- Compound cherry-picking service is provided
What We Deliver
- Delivered within 2 weeks in any customer-preferred format
- Powders, dry films or DMSO solutions formatted in vials, 96 or 384-well plates
- All compounds have a minimum purity of 90% assessed by 1H NMR and HPLC
- Analytical data is provided
BOC Sciences provides professional, rapid and high-quality services of Matrix Metalloproteinase Focused Library design at competitive prices for global customers. Personalized and customized services of Matrix Metalloproteinase Focused Library design can satisfy any innovative scientific study demands. Our clients have direct access to our staff and prompt feedback to their inquiries. If you are interested in our services, please contact us immediately!
Reference
- Shirian, J.; et al. Converting a broad matrix metalloproteinase family inhibitor into a specific inhibitor of MMP-9 and MMP-14. FEBS Letters. 2018. 592(7): 1122-1134.
