Therapeutic Targets Database
BIDD Pharmainformatics Databases


TTD Target ID: TTDC00104

Target Information
Name72 kDa type IV collagenase    
Type of targetDiscontinued target    
Synonyms72 kDa gelatinase    
Gelatinase A    
Matrix metalloproteinase 2    
Matrix metalloproteinase-2    
DiseaseBrain Cancer
[ICD9: 191   ICD10: C71]
Breast cancer
[ICD9: 174, 175   ICD10: C50]
Cancer, unspecific
[ICD9: 140-229   ICD10: C00-C96]
Hepatocellular carcinoma
[ICD9: 155   ICD10: C22.0]
Hormone-refractory Prostate cancer
[ICD9: 185   ICD10: C61]
Kaposi's Sarcoma
[ICD9: 176   ICD10: C46]
Lung Cancer
[ICD9: 162   ICD10: C33-C34]
Non-small Cell Lung Cancer
[ICD9: 162   ICD10: C33, C34]
[ICD9: 715   ICD10: M15-M19, M47]
Pancreatic Cancer
[ICD9: 157   ICD10: C25]
Prostate cancer
[ICD9: 185   ICD10: C61]
Renal Cell Carcinoma
[ICD9: 189   ICD10: C64]
Smooth muscle hyperplasia[16]
Drug(s)BB-3644Discontinued in Phase ICancer/Tumors[17][18]
BMS 275291Discontinued in Phase IIINon-small Cell Lung Cancer, Hormone-refractory Prostate Cancer, Kaposi's Sarcoma[7][8][19][17]
BatimastatDiscontinued in Phase ICancers[17]
MarimastatDiscontinued in Phase IIIPancreatic Cancer, Lung Cancer[20][11][12][17]
MetastatDiscontinued in Phase IIKaposi's Sarcoma[17]
NeovastatDiscontinued in Phase IIICancer/psoriasis/opthalmologic[21][14][15]
NeovastatSuspended in Phase IIINon-small Cell Lung Cancer (NSCLC), Renal Cell Carcinoma[21][14][15]
PG-116800Suspended in Phase IIAcute and chronic heart failure[22]
PrinomastatDiscontinued in Phase IIIBrain Cancer[23][1][2][3][17]
PrinomastatTrial haltedLung Cancer, Prostate Cancer[23][1][2][3][17]
TanomastatDiscontinued in Phase IIIPancreatic Cancer, Lung Cancer, Ovarian Cancer, Osteoarthritis[24][25][26][17]
BioChemical ClassHydrolases acting on peptide bonds (Peptidases)    
EC NumberEC
UniProt IDP08253
PDB Structure1CK7; 1CXW; 1EAK; 1GEN; 1GXD; 1HOV; 1J7M; 1KS0; 1QIB; 1RTG; 3AYU.    
Related US Patent6,265,432
Target ValidationClick to Find Target Validation Information.    
QSAR ModelClick to Find Target QSAR Model.    
Inhibitor (+/-)5-[28]
2- (4'-chloro-biphenyl-4-sulfonyl)-pentanoic acid[29]
2- (Biphenyl-4-ylsulfonyl)N-hydroxybenzamide[30]
3- (4-[31]
3- (4-Phenylethynylbenzoyl)nonanoic acid[31]
4- (4-[31]
5- (4-Phenoxy-phenyl)-pyrimidine-2,4,6-trione[32]
BMS 275291[7][8][19][17]
Clinopodic acid C[40]
N-Hydroxy-2- (4-phenoxy-benzenesulfonyl)benzamide[30]
N-hydroxy-3- (2-oxo-2H-chromen-3-yl)propanamide[45]
N-hydroxy-3- (6-methoxy-2-oxo-2H-chromen-3-yl)[45]
Roche 28-2653[50]
[2- (Biphenyl-4-sulfonyl)phenyl]acetic Acid[30]
cis-2-aminocyclohexylcarbamoylphosphonic acid[54]
folate gamma-L-proline-hydroxamic acid[55]
folate gamma-hydroxamic acid[55]
lithospermic acid[40]
methotrexate gamma-L-proline-hydroxamic acid[55]
methotrexate gamma-hydroxamic acid[55]
BMS 275291[7][8][19][17]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1Inhibition 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 2Delayed 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 3Pharmacoproteomics 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 4Association of MMP-2 activation potential with metastatic progression in human breast cancer cell lines independent of MMP-2 production. J Natl Cancer Inst. 1993 Nov 3;85(21):1758-64. To Reference
Ref 5Strategies for MMP inhibition in cancer: innovations for the post-trial era. Nat Rev Cancer. 2002 Sep;2(9):657-72. To Reference
Ref 6Chemopreventive allylthiopyridazines inhibit invasion, migration and angiogenesis in hepatocarcinoma cells. Int J Oncol. 2003 Dec;23(6):1645-50. 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 9Am 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 10Novel investigational drugs for gastric cancer. Expert Opin Investig Drugs. 2009 Jul;18(7):945-55. To Reference
Ref 11Matrix metalloproteinase-2 involvement in breast cancer progression: a mini-review. Med Sci Monit. 2009 Feb;15(2):RA32-40. To Reference
Ref 12Matrix 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 13Shark cartilage extract. No effect on bronchial carcinoma. Med Monatsschr Pharm. 2007 Sep;30(9):351. To Reference
Ref 14Neovastat (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 15Int J Oncol. 2002 Feb;20(2):299-303.The effect of Neovastat (AE-941) on an experimental metastatic bone tumor model. To Reference
Ref 16Autocrine production of matrix metalloproteinase-2 is required for human airway smooth muscle proliferation. Am J Physiol. 1999 Dec;277(6 Pt 1):L1109-17. To Reference
Ref 1716498445 To Reference
Ref 18A phase I and pharmacological study of the matrix metalloproteinase inhibitor BB-3644 in patients with solid tumours. Br J Cancer. 2004 Feb 23;90(4):800-4. To Reference
Ref 19Randomized phase III study of matrix metalloproteinase inhibitor BMS-275291 in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: National Cancer Institute of Canada-Clinical Trials Group Study BR.18. J Clin Oncol. 2005 Apr 20;23(12):2831-9. To Reference
Ref 20Metalloelastase (MMP-12) induced inflammatory response in mice airways: effects of dexamethasone, rolipram and marimastat. Eur J Pharmacol. 2007 Mar 15;559(1):75-81. Epub 2006 Dec 12. To Reference
Ref 21Semin Oncol. 2001 Dec;28(6):620-5.Neovastat, a naturally occurring multifunctional antiangiogenic drug, in phase III clinical trials. To Reference
Ref 22Emerging drugs for acute and chronic heart failure: current and future developments. Expert Opin Emerg Drugs. 2007 Mar;12(1):75-95. To Reference
Ref 23AG-3340 (Agouron Pharmaceuticals Inc). IDrugs. 2000 Mar;3(3):336-45. To Reference
Ref 24Radiation therapy and biological compounds for consolidation therapy in advanced ovarian cancer. Int J Gynecol Cancer. 2008 Mar-Apr;18 Suppl 1:44-6. To Reference
Ref 25Conflicting results from clinical observations and murine models: what is the role of plasminogen activators in tumor growth? J Natl Cancer Inst. 2006 Jun 7;98(11):726-7. To Reference
Ref 26A phase III randomized trial of BAY 12-9566 (tanomastat) as maintenance therapy in patients with advanced ovarian cancer responsive to primary surgery and paclitaxel/platinum containing chemotherapy: a National Cancer Institute of Canada Clinical Trials Group Study. Gynecol Oncol. 2006 Aug;102(2):300-8. Epub 2006 Jan 25. To Reference
Ref 27Emerging disease-modifying therapies for the treatment of motor neuron disease/amyotropic lateral sclerosis. Expert Opin Emerg Drugs. 2007 May;12(2):229-52. To Reference
Ref 28Bioorg 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 29Bioorg 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 30J 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 31J 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 32Bioorg 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 33Prinomastat, a hydroxamate-based matrix metalloproteinase inhibitor. A novel pharmacological approach for tissue remodelling-related diseases. Expert Opin Investig Drugs. 2000 Sep;9(9):2159-65. To Reference
Ref 34Suppression of adjuvant arthritis of rats by a novel matrix metalloproteinase-inhibitor. Br J Pharmacol. 2000 Dec;131(8):1513-20. To Reference
Ref 35Bioorg Med Chem Lett. 1998 Jun 16;8(12):1443-8.Broad spectrum matrix metalloproteinase inhibitors: an examination of succinamide hydroxamate inhibitors with P1 C alpha gem-disubstitution. To Reference
Ref 36Advances in ischemic stroke treatment: neuroprotective and combination therapies. Expert Opin Emerg Drugs. 2007 Mar;12(1):97-112. To Reference
Ref 37Inhibition of gelatinase A (MMP-2) by batimastat and captopril reduces tumor growth and lung metastases in mice bearing Lewis lung carcinoma. Int J Cancer. 1999 May 31;81(5):761-6. To Reference
Ref 38Bioorg 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 39J Med Chem. 2000 Feb 10;43(3):305-41.Protease inhibitors: current status and future prospects. To Reference
Ref 40J Nat Prod. 2009 Aug;72(8):1379-84.Matrix metalloproteinase-2 inhibitors from Clinopodium chinense var. parviflorum. To Reference
Ref 41Bioorg Med Chem Lett. 2009 Aug 1;19(15):4171-4. Epub 2009 Jun 2.Regioselective synthesis of methylated epigallocatechin gallate via nitrobenzenesulfonyl (Ns) protecting group. To Reference
Ref 42J 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 43Bioorg 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 44Bioorg. Med. Chem. Lett. 5(6):539-542 (1995) To Reference
Ref 45Bioorg 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 46J Med Chem. 2006 Feb 9;49(3):923-31.Structural insight into the stereoselective inhibition of MMP-8 by enantiomeric sulfonamide phosphonates. To Reference
Ref 47J Med Chem. 2004 Jun 3;47(12):3065-74.A molecular basis for the selectivity of thiadiazole urea inhibitors with stromelysin-1 and gelatinase-A from generalized born molecular dynamics simulations. To Reference
Ref 48Bioorg 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 49Bioorg. Med. Chem. Lett. 7(17):2299-2302 (1997) To Reference
Ref 50The 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 51J 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 52Overington 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 53Bioorg 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 54J Med Chem. 2008 Mar 13;51(5):1406-14. Epub 2008 Feb 8.Carbamoylphosphonate matrix metalloproteinase inhibitors 6: cis-2-aminocyclohexylcarbamoylphosphonic acid, a novel orally active antimetastatic matrix metalloproteinase-2 selective inhibitor--synthesis and pharmacodynamic and pharmacokinetic analysis. To Reference
Ref 55Bioorg 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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