Therapeutic Targets Database
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TTD Target ID: TTDC00076

Target Information
Name92 kDa type IV collagenase    
Type of targetDiscontinued target    
Synonyms92 kDa gelatinase    
GELB    
Gelatinase B    
MMP-9    
Matrix metalloproteinase 9    
Matrix metalloproteinase-9    
DiseaseAdvanced lung cancer
[ICD9: 140-229, 162   ICD10: C00-C96, C33-C34]
[1]
Atherosclerosis
[ICD9: 414.0, 440   ICD10: I70]
[2]
Brain Cancer
[ICD9: 191   ICD10: C71]
[3][4][5]
Guillain-Barre syndrome[6]
Hormone-refractory Prostate cancer
[ICD9: 185   ICD10: C61]
[7][8]
Kaposi's Sarcoma
[ICD9: 176   ICD10: C46]
[7][8]
Lung Cancer
[ICD9: 162   ICD10: C33-C34]
[3][4][5]
Multiple sclerosis
[ICD9: 340   ICD10: G35]
[9]
Non-small Cell Lung Cancer
[ICD9: 162   ICD10: C33, C34]
[7][8]
Osteoarthritis
[ICD9: 715   ICD10: M15-M19, M47]
[10]
Pancreatic Cancer
[ICD9: 157   ICD10: C25]
[11][12][13]
Prostate cancer
[ICD9: 185   ICD10: C61]
[14][15][16]
Renal Cell Carcinoma
[ICD9: 189   ICD10: C64]
[14][15][16]
Restenosis[2]
Rheumatoid arthritis, unspecified
[ICD9: 710-719, 714   ICD10: M00-M25, M05-M06]
[17]
Drug(s)GS-5745Phase ISolid Tumors
GS-5745Phase IUlcerative Colitis
NeovastatDiscontinued in Phase IIICancer/psoriasis/opthalmologic[18][15][16]
NeovastatSuspended in Phase IIINon-small Cell Lung Cancer (NSCLC), Renal Cell Carcinoma[18][15][16]
PG-116800Suspended in Phase IIAcute and chronic heart failure[19]
BioChemical ClassHydrolases acting on peptide bonds (Peptidases)    
EC NumberEC 3.4.24.35
PathwayBladder cancer
Leukocyte transendothelial migration
Pathways in cancer
UniProt IDP14780
PDB Structure1GKC; 1GKD; 1ITV; 1L6J; 1LKG; 2OVX; 2OVZ; 2OW0; 2OW1; 2OW2; 4H1Q; 4H2E; 4H3X; 4H82; 4HMA.    
FunctionCould play a role in bone osteoclastic resorption.    
SequenceMSLWQPLVLVLLVLGCCFAAPRQRQSTLVLFPGDLRTNLTDRQLAEEYLYRYGYTRVAEM RGESKSLGPALLLLQKQLSLPETGELDSATLKAMRTPRCGVPDLGRFQTFEGDLKWHHHN ITYWIQNYSEDLPRAVIDDAFARAFALWSAVTPLTFTRVYSRDADIVIQFGVAEHGDGYP FDGKDGLLAHAFPPGPGIQGDAHFDDDELWSLGKGVVVPTRFGNADGAACHFPFIFEGRS YSACTTDGRSDGLPWCSTTANYDTDDRFGFCPSERLYTQDGNADGKPCQFPFIFQGQSYS ACTTDGRSDGYRWCATTANYDRDKLFGFCPTRADSTVMGGNSAGELCVFPFTFLGKEYST CTSEGRGDGRLWCATTSNFDSDKKWGFCPDQGYSLFLVAAHEFGHALGLDHSSVPEALMY PMYRFTEGPPLHKDDVNGIRHLYGPRPEPEPRPPTTTTPQPTAPPTVCPTGPPTVHPSER PTAGPTGPPSAGPTGPPTAGPSTATTVPLSPVDDACNVNIFDAIAEIGNQLYLFKDGKYW RFSEGRGSRPQGPFLIADKWPALPRKLDSVFEEPLSKKLFFFSGRQVWVYTGASVLGPRR LDKLGLGADVAQVTGALRSGRGKMLLFSGRRLWRFDVKAQMVDPRSASEVDRMFPGVPLD THDVFQYREKAYFCQDRFYWRVSSRSELNQVDQVGYVTYDILQCPED
Related US Patent6,310,084
6,541,489
6,624,144
6,630,501
6,667,388
Target ValidationClick to Find Target Validation Information.    
QSAR ModelClick to Find Target QSAR Model.    
Inhibitor (+/-)5-[20]
2- (4'-chloro-biphenyl-4-sulfonyl)-pentanoic acid[21]
2- (Biphenyl-4-ylsulfonyl)N-hydroxybenzamide[22]
2- (biphenyl-4-ylsulfonamido)pentanedioic acid[23]
2-Amino-N,3,3-Trimethylbutanamide[24]
3- (4-[25]
3- (4-Phenylethynylbenzoyl)nonanoic acid[25]
4-amino-3- (4-[23]
5- (4-Phenoxy-phenyl)-pyrimidine-2,4,6-trione[26]
5-Biphenyl-4-yl-5-ethyl-pyrimidine-2,4,6-trione[26]
5-Biphenyl-4-yl-5-hexyl-pyrimidine-2,4,6-trione[26]
5-Hexyl-5-phenyl-pyrimidine-2,4,6-trione[26]
5-Methyl-5-phenyl-pyrimidine-2,4,6-trione[26]
BAY-12-9566[17]
CGS-27023A[27]
CIPEMASTAT[28]
CURCUMIN[29]
IK-682[30]
ILOMASTAT[31]
N-Hydroxy-2- (4-phenoxy-benzenesulfonyl)benzamide[22]
N-hydroxy-2,3-bis (phenylsulfonamido)propanamide[32]
N-hydroxy-3- (2-oxo-2H-chromen-3-yl)propanamide[33]
N-hydroxy-3- (6-methoxy-2-oxo-2H-chromen-3-yl)[33]
Neovastat[18][15][16]
PG-116800[19]
RO-319790[34]
RS-130830[35]
Ro 28-2653[36]
Ro-32-3555[37]
Ro-37-9790[37]
Roche 28-2653[36]
SC-44463[38]
SR-973[39]
UK-356618[40]
[2- (Biphenyl-4-sulfonyl)phenyl]acetic Acid[22]
carboxylated glucosamine[41]
folate gamma-hydroxamic acid[42]
methotrexate gamma-L-phenylalaninehydroxamic acid[42]
methotrexate gamma-L-proline-hydroxamic acid[42]
methotrexate gamma-hydroxamic acid[42]
MultitargetNeovastat[18][15][16]
PG-116800[19]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1Phase I trial of Marimastat, a novel matrix metalloproteinase inhibitor, administered orally to patients with advanced lung cancer. J Clin Oncol. 1998 Jun;16(6):2150-6. To Reference
Ref 2Targeted disruption of the matrix metalloproteinase-9 gene impairs smooth muscle cell migration and geometrical arterial remodeling. Circ Res. 2002 Nov 1;91(9):852-9. To Reference
Ref 3Inhibition of gelatinase activity reduces neural injury in an ex vivo model of hypoxia-ischemia. Neuroscience. 2009 Jun 2;160(4):755-66. Epub 2009 Mar 9. To Reference
Ref 4Delayed administration of a matrix metalloproteinase inhibitor limits progressive brain injury after hypoxia-ischemia in the neonatal rat. J Neuroinflammation. 2008 Aug 11;5:34. To Reference
Ref 5Pharmacoproteomics of a metalloproteinase hydroxamate inhibitor in breast cancer cells: dynamics of membrane type 1 matrix metalloproteinase-mediated membrane protein shedding. Mol Cell Biol. 2008 Aug;28(15):4896-914. Epub 2008 May 27. To Reference
Ref 6Matrix metalloproteinase-9 is increased and correlates with severity in Guillain-Barr¨¦ syndrome. Neurology. 1999 Nov 10;53(8):1683-91. To Reference
Ref 7Phase 1/2 trial of BMS-275291 in patients with human immunodeficiency virus-related Kaposi sarcoma: a multicenter trial of the AIDS Malignancy Consortium. Cancer. 2008 Mar 1;112(5):1083-8. To Reference
Ref 8Randomized phase II feasibility study of combining the matrix metalloproteinase inhibitor BMS-275291 with paclitaxel plus carboplatin in advanced non-small cell lung cancer. Lung Cancer. 2004 Dec;46(3):361-8. To Reference
Ref 9Gelatinase B/matrix metalloproteinase-9 cleaves interferon-beta and is a target for immunotherapy. Brain. 2003 Jun;126(Pt 6):1371-81. To Reference
Ref 10Am J Physiol Heart Circ Physiol. 2006 Jun;290(6):H2522-7. Epub 2006 Jan 20.Selective matrix metalloproteinase inhibition attenuates progression of left ventricular dysfunction and remodeling in dogs with chronic heart failure. To Reference
Ref 11Novel investigational drugs for gastric cancer. Expert Opin Investig Drugs. 2009 Jul;18(7):945-55. To Reference
Ref 12Matrix metalloproteinase-2 involvement in breast cancer progression: a mini-review. Med Sci Monit. 2009 Feb;15(2):RA32-40. To Reference
Ref 13Matrix metalloproteinase inhibition as a novel anticancer strategy: a review with special focus on batimastat and marimastat. Pharmacol Ther. 1997;75(1):69-75. To Reference
Ref 14Shark cartilage extract. No effect on bronchial carcinoma. Med Monatsschr Pharm. 2007 Sep;30(9):351. To Reference
Ref 15Neovastat (AE-941) inhibits the airway inflammation and hyperresponsiveness in a murine model of asthma. J Microbiol. 2005 Feb;43(1):11-6. To Reference
Ref 16Int J Oncol. 2002 Feb;20(2):299-303.The effect of Neovastat (AE-941) on an experimental metastatic bone tumor model. To Reference
Ref 17Suppression of adjuvant arthritis of rats by a novel matrix metalloproteinase-inhibitor. Br J Pharmacol. 2000 Dec;131(8):1513-20. To Reference
Ref 18Semin Oncol. 2001 Dec;28(6):620-5.Neovastat, a naturally occurring multifunctional antiangiogenic drug, in phase III clinical trials. To Reference
Ref 19Emerging drugs for acute and chronic heart failure: current and future developments. Expert Opin Emerg Drugs. 2007 Mar;12(1):75-95. To Reference
Ref 20Bioorg Med Chem Lett. 2009 Oct 1;19(19):5760-3. Epub 2009 Aug 6.The identification of beta-hydroxy carboxylic acids as selective MMP-12 inhibitors. To Reference
Ref 21Bioorg Med Chem Lett. 2006 Jun 15;16(12):3096-100. Epub 2006 May 2.Synthesis and SAR of alpha-sulfonylcarboxylic acids as potent matrix metalloproteinase inhibitors. To Reference
Ref 22J Med Chem. 2009 Oct 22;52(20):6347-61.Design, synthesis, biological evaluation, and NMR studies of a new series of arylsulfones as selective and potent matrix metalloproteinase-12 inhibitors. To Reference
Ref 23Bioorg Med Chem. 2009 Feb 1;17(3):1101-8. Epub 2008 Mar 8.Ranking the selectivity of PubChem screening hits by activity-based protein profiling: MMP13 as a case study. To Reference
Ref 24Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. To Reference
Ref 25J Med Chem. 2006 Jan 26;49(2):456-8.Selective inhibition of matrix metalloproteinase isozymes and in vivo protection against emphysema by substituted gamma-keto carboxylic acids. To Reference
Ref 26Bioorg Med Chem Lett. 2001 Apr 23;11(8):969-72.Novel 5,5-disubstitutedpyrimidine-2,4,6-triones as selective MMP inhibitors. To Reference
Ref 27Bioorg Med Chem Lett. 1999 Jun 21;9(12):1691-6.Picking the S1, S1' and S2' pockets of matrix metalloproteinases. A niche for potent acyclic sulfonamide inhibitors. To Reference
Ref 28J Med Chem. 2000 Feb 10;43(3):305-41.Protease inhibitors: current status and future prospects. To Reference
Ref 29Bioorg Med Chem. 2009 Feb 1;17(3):1290-6. Epub 2009 Jan 6.Synthesis and biological evaluation of curcuminoid pyrazoles as new therapeutic agents in inflammatory bowel disease: effect on matrix metalloproteinases. To Reference
Ref 30J Med Chem. 2002 Nov 7;45(23):4954-7.Discovery of gamma-lactam hydroxamic acids as selective inhibitors of tumor necrosis factor alpha converting enzyme: design, synthesis, and structure-activity relationships. To Reference
Ref 31Bioorg Med Chem. 2008 Sep 15;16(18):8745-59. Epub 2008 Jul 20.Introduction of the 4-(4-bromophenyl)benzenesulfonyl group to hydrazide analogs of Ilomastat leads to potent gelatinase B (MMP-9) inhibitors with improved selectivity. To Reference
Ref 32Bioorg Med Chem Lett. 2008 Jun 1;18(11):3333-7. Epub 2008 Apr 16.Novel bis-(arylsulfonamide) hydroxamate-based selective MMP inhibitors. To Reference
Ref 33Bioorg Med Chem. 2008 Jan 1;16(1):530-5. Epub 2007 Sep 14.Chromen-based TNF-alpha converting enzyme (TACE) inhibitors: design, synthesis, and biological evaluation. To Reference
Ref 34Bioorg Med Chem Lett. 1998 May 19;8(10):1163-8.The asymmetric synthesis and in vitro characterization of succinyl mercaptoalcohol and mercaptoketone inhibitors of matrix metalloproteinases. To Reference
Ref 35Bioorg Med Chem Lett. 2005 Feb 15;15(4):1101-6.Structure-based design of potent and selective inhibitors of collagenase-3 (MMP-13). To Reference
Ref 36The new synthetic matrix metalloproteinase inhibitor (Roche 28-2653) reduces tumor growth and prolongs survival in a prostate cancer standard rat model. Oncogene. 2002 Mar 27;21(13):2089-96. To Reference
Ref 37Bioorg. Med. Chem. Lett. 7(17):2299-2302 (1997) To Reference
Ref 38J Med Chem. 2001 Oct 11;44(21):3347-50.Design and synthesis of a series of (2R)-N(4)-hydroxy-2-(3-hydroxybenzyl)-N(1)- [(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]butanediamide derivatives as potent, selective, and orally bioavailable aggrecanase inhibitors. To Reference
Ref 39Bioorg Med Chem Lett. 2006 May 1;16(9):2357-63. Epub 2006 Feb 10.Synthesis and evaluation of succinoyl-caprolactam gamma-secretase inhibitors. To Reference
Ref 40J Med Chem. 2003 Jul 31;46(16):3514-25.A potent, selective inhibitor of matrix metalloproteinase-3 for the topical treatment of chronic dermal ulcers. To Reference
Ref 41Bioorg Med Chem Lett. 2006 Jun 15;16(12):3105-10. Epub 2006 Apr 17.Carboxy derivatized glucosamine is a potent inhibitor of matrix metalloproteinase-9 in HT1080 cells. To Reference
Ref 42Bioorg Med Chem. 2007 Feb 1;15(3):1266-74. Epub 2006 Nov 14.Methotrexate gamma-hydroxamate derivatives as potential dual target antitumor drugs. To Reference



 

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Professor in Department of Pharmacy
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