MMpI: A WideRange of Available Compounds of Matrix Metalloproteinase Inhibitors

Abstract

Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases involved in the regulation of the extracellular signaling and structural matrix environment of cells and tissues. MMPs are considered as promising targets for the treatment of many diseases. Therefore, creation of database on the inhibitors of MMP would definitely accelerate the research activities in this area due to its implication in above-mentioned diseases and associated limitations in the first and second generation inhibitors. In this communication, we report the development of a new MMpI database which provides resourceful information for all researchers working in this field. It is a web-accessible, unique resource that contains detailed information on the inhibitors of MMP including small molecules, peptides and MMP Drug Leads. The database contains entries of ~3000 inhibitors including ~72 MMP Drug Leads and ~73 peptide based inhibitors. This database provides the detailed molecular and structural details which are necessary for the drug discovery and development. The MMpI database contains physical properties, 2D and 3D structures (mol2 and pdb format files) of inhibitors of MMP. Other data fields are hyperlinked to PubChem, ChEMBL, BindingDB, DrugBank, PDB, MEROPS and PubMed. The database has extensive searching facility with MMpI ID, IUPAC name, chemical structure and with the title of research article. The MMP inhibitors provided in MMpI database are optimized using Python-based Hierarchical Environment for Integrated Xtallography (Phenix) software. MMpI Database is unique and it is the only public database that contains and provides the complete information on the inhibitors of MMP. Database URL: http://clri.res.in/subramanian/databases/mmpi/index.php.

Matrix Metalloproteinases Shape the Tumor Microenvironment in Cancer Progression

“…Although MMPs on the cell surface or in the extracellular compartment are, in principle, druggable, more than 50 different MMP inhibitors have so far proven to be unsuccessful in clinical studies [ 17 , 479 , 480 , 481 ]. In a phase I/IIa clinical trial [ 482 ] started in January 2018, the drug BT1718 is being studied in adult patients with advanced solid tumors.…”

Fluorescent probes for visualizing ROS-associated proteins in disease

“…Consequently, several ROS-associated MMPs are considered potential diagnostic and prognostic biomarkers for cancers. 64–66 …”

“…57,63 Consequently, several ROS-associated MMPs are considered potential diagnostic and prognostic biomarkers for cancers. [64][65][66] Until now, a large number of MMP-responsive uorescent probes for imaging have been successfully developed, all of which were designed by incorporating chromophore-modied substrates and a quencher. 67 Youn et al developed a soluble probe, 16, for detecting the activity of MMP-3 from serum to monitor the progress of rheumatoid arthritis (Fig.…”

Beyond EGFR inhibition: multilateral combat strategies to stop the progression of head and neck cancer

“…ECM degradation is caused by proteolytic enzymes, typically MMPs, that are secreted by tumor cells. MMPs are classified into collagenases (MMP-1, -8, and -13), gelatinases (MMP-2 and -9), stromelysins (MMP-3, -10, -11, and -27), matrilysins (MMP-7 and -26), enamelysin (MMP-20), metalloelastase (MMP-12), membrane-type MMPs (MMP-14 to 17, -24, and -25), and others (MMP-19, -21, -23, and -28) by dependent substrates 67 . In particular, MT1-MMP (MMP-14) is a zinc-dependent proteinase expressed in the cell membrane that is involved in the promotion of tumor growth and metastasis 68 .…”