Novel Matrix Metalloproteinase Inhibitors
Matrix Metalloproteinases (MMPs) are zinc containing hydrolytic enzymes that are able to degrade extracellular matrix components such as collagen. MMP’s have been implicated in a variety of diseases, including cancer, arthritis, inflammatory disease, and heart disease. Despite intensive research and clinical testing of MMP inhibitors, the only approved MMP inhibitor is a tetracycline for the treatment of periodontitis. UCSD researchers have developed a novel series of organic compounds that are potent inhibitors of MMPs. While most MMP inhibitors in development are based on small peptide mimetics that chelate the zinc ion using a hydroxamic acid moiety, the UCSD researchers designed a novel class of zinc-binding groups (ZBGs) by rational drug design. The binding mode of the ZBGs was optimized using structural, spectroscopic, and computational studies of the compounds bound to an inorganic zinc model complex for MMP’s. These new inhibitors are up to 700-fold more potent than acetohydroxamic acid in MMP binding assays and are expected to have better oral availability and pharmacokinetics when compared with hydroxamate-based compounds. These ZBG inhibitors have commercial applications in drug design against MMP’s and other metalloproteins related to human disease, such as histone deacetylases.
Patent Number: US7705164B2
Application Number: US2006568505A
Inventor: Puerta, David T. | Cohen, Seth M. | Lewis, Jana A.
Priority Date: 29 Apr 2004
Priority Number: US7705164B2
Application Date: 22 Aug 2007
Publication Date: 27 Apr 2010
IPC Current: C07D031500 | A61K0031167 | A61K003135 | A61K0031435 | C07D021362 | C07D021369 | C07D030936 | C07D030938 | C07D030940
US Class: 549420 | 546261 | 549418
Assignee Applicant: The Regents of the University of California
Title: Metalloprotein inhibitors
Usefulness: Metalloprotein inhibitors
Summary: In pharmaceutical compositions for treating pathology associated with metalloprotein activity e.g. elevated metalloprotein activity, including cancer, inflammation, myocardial infarction (claimed), anthrax pathogenesis, arthritis, rheumatoid arthritis, restenosis, aortic aneurism, irritable bowel disease, glomerular nephritis, multiple sclerosis, stroke, diabetes, bacterial meningitis, graft versus host disease, Hodgkin's lymphoma, osteosarcoma, germ cell tumor, lung cancer, myelodysplastic syndrome, Ewing's sarcoma, Paget's disease, epidermal scars and periodontal disease.
Novelty: New hydroxypyridinone, hydroxypyridinethione, pyrone and thiopyrone compounds useful as metalloprotein inhibitors for treating e.g. cancer and inflammation
Disease Diagnostic/Treatment
Cancer/Tumor
7705164
Additional Technologies by these Inventors Tech ID/UC Case 19604/2004-102-0 Related Cases 2004-102-0
USA
