BIOMAT Database Logo BIOMAT Database Logo

Structure-based approach to nanomolar, water soluble matrix metalloproteinases inhibitors (MMPIs). 2010

Emanuele Attolino, and Vito Calderone, and Elisa Dragoni, and Marco Fragai, and Barbara Richichi, and Claudio Luchinat, and Cristina Nativi
ProtEra s.r.l. viale delle Idee, 22 I-50019 Sesto F.no (FI), Italy.

N-arylsulfonyl-based MMPs inhibitors (MMPIs) are among the most prominent inhibitors possessing nanomolar affinity. However, their poor bioavailability remains critical for the drug development of this family of molecules. The structural analysis of the complex of NNGH (the most representative member of the family) with MMP-12 provided us with the basis to effectively design simple NNGH analogues with enhanced solubility in water. Following this approach, the sec-butyl residue, not directly involved in the binding with MMP, has been replaced with hydrophilic residues thus yielding new potent inhibitors soluble in water.

UI MeSH Term Description Entries
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D011480 Protease Inhibitors Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES). Antiprotease,Endopeptidase Inhibitor,Endopeptidase Inhibitors,Peptidase Inhibitor,Peptidase Inhibitors,Peptide Hydrolase Inhibitor,Peptide Hydrolase Inhibitors,Peptide Peptidohydrolase Inhibitor,Peptide Peptidohydrolase Inhibitors,Protease Antagonist,Protease Antagonists,Antiproteases,Protease Inhibitor,Antagonist, Protease,Antagonists, Protease,Hydrolase Inhibitor, Peptide,Hydrolase Inhibitors, Peptide,Inhibitor, Endopeptidase,Inhibitor, Peptidase,Inhibitor, Peptide Hydrolase,Inhibitor, Peptide Peptidohydrolase,Inhibitor, Protease,Inhibitors, Endopeptidase,Inhibitors, Peptidase,Inhibitors, Peptide Hydrolase,Inhibitors, Peptide Peptidohydrolase,Inhibitors, Protease,Peptidohydrolase Inhibitor, Peptide,Peptidohydrolase Inhibitors, Peptide
D012995 Solubility The ability of a substance to be dissolved, i.e. to form a solution with another substance. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed) Solubilities
D013237 Stereoisomerism The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed) Molecular Stereochemistry,Stereoisomers,Stereochemistry, Molecular,Stereoisomer
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D013450 Sulfones Sulfone
D014867 Water A clear, odorless, tasteless liquid that is essential for most animal and plant life and is an excellent solvent for many substances. The chemical formula is hydrogen oxide (H2O). (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Hydrogen Oxide
D015394 Molecular Structure The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. Structure, Molecular,Molecular Structures,Structures, Molecular
D049329 Nanostructures Materials which have structured components with at least one dimension in the range of 1 to 100 nanometers. These include NANOCOMPOSITES; NANOPARTICLES; NANOTUBES; and NANOWIRES. Nanomaterials,Nanostructured Materials,Material, Nanostructured,Materials, Nanostructured,Nanomaterial,Nanostructure,Nanostructured Material
D061965 Matrix Metalloproteinase Inhibitors Compounds that inhibit the enzyme activity or activation of MATRIX METALLOPROTEINASES. Collagenase Inhibitor,Gelatinase Inhibitor,MMP Inhibitor,Matrix Metalloproteinase Inhibitor,Collagenase Inhibitors,Gelatinase Inhibitors,MMP Inhibitors,Stromelysin Inhibitors,Inhibitor, Collagenase,Inhibitor, Gelatinase,Inhibitor, MMP,Inhibitor, Matrix Metalloproteinase,Inhibitors, Collagenase,Inhibitors, Gelatinase,Inhibitors, MMP,Inhibitors, Matrix Metalloproteinase,Inhibitors, Stromelysin,Metalloproteinase Inhibitor, Matrix,Metalloproteinase Inhibitors, Matrix

Related Publications

Emanuele Attolino, and Vito Calderone, and Elisa Dragoni, and Marco Fragai, and Barbara Richichi, and Claudio Luchinat, and Cristina Nativi
Synthesis and binding monitoring of a new nanomolar PAMAM-based matrix metalloproteinases inhibitor (MMPIs).
January 2017, Bioorganic & medicinal chemistry,
Emanuele Attolino, and Vito Calderone, and Elisa Dragoni, and Marco Fragai, and Barbara Richichi, and Claudio Luchinat, and Cristina Nativi
Molecular Imaging Probes Based on Matrix Metalloproteinase Inhibitors (MMPIs).
August 2019, Molecules (Basel, Switzerland),
Emanuele Attolino, and Vito Calderone, and Elisa Dragoni, and Marco Fragai, and Barbara Richichi, and Claudio Luchinat, and Cristina Nativi
Identifying simultaneous matrix metalloproteinases/soluble epoxide hydrolase inhibitors.
March 2022, Molecular and cellular biochemistry,
Emanuele Attolino, and Vito Calderone, and Elisa Dragoni, and Marco Fragai, and Barbara Richichi, and Claudio Luchinat, and Cristina Nativi
Sulfur-based inhibitors for matrix metalloproteinases.
January 1992, Matrix (Stuttgart, Germany). Supplement,
Emanuele Attolino, and Vito Calderone, and Elisa Dragoni, and Marco Fragai, and Barbara Richichi, and Claudio Luchinat, and Cristina Nativi
Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry.
May 2003, Circulation research,
Emanuele Attolino, and Vito Calderone, and Elisa Dragoni, and Marco Fragai, and Barbara Richichi, and Claudio Luchinat, and Cristina Nativi
Potent mechanism-based inhibitors for matrix metalloproteinases.
October 2005, The Journal of biological chemistry,
Emanuele Attolino, and Vito Calderone, and Elisa Dragoni, and Marco Fragai, and Barbara Richichi, and Claudio Luchinat, and Cristina Nativi
Highly water-soluble matrix metalloproteinases inhibitors and their effects in a rat adjuvant-induced arthritis model.
August 2002, Bioorganic & medicinal chemistry,
Emanuele Attolino, and Vito Calderone, and Elisa Dragoni, and Marco Fragai, and Barbara Richichi, and Claudio Luchinat, and Cristina Nativi
Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases in Echinoderms: Structure and Possible Functions.
September 2021, Cells,
Emanuele Attolino, and Vito Calderone, and Elisa Dragoni, and Marco Fragai, and Barbara Richichi, and Claudio Luchinat, and Cristina Nativi
Structure-based design of low-nanomolar PIM kinase inhibitors.
February 2015, Bioorganic & medicinal chemistry letters,
Emanuele Attolino, and Vito Calderone, and Elisa Dragoni, and Marco Fragai, and Barbara Richichi, and Claudio Luchinat, and Cristina Nativi
Design and Synthesis of Ionic Liquid-Based Matrix Metalloproteinase Inhibitors (MMPIs): A Simple Approach to Increase Hydrophilicity and to Develop MMPI-Coated Gold Nanoparticles.
March 2019, ChemMedChem,
Copied contents to your clipboard!