Therapeutic Targets Database
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TTD Target ID: TTDC00147

Target Information
NameInterstitial collagenase    
Type of targetDiscontinued target    
SynonymsFibroblast collagenase    
MMP-1    
Matrix metalloproteinase-1    
DiseaseCancer, unspecific
[ICD9: 140-229   ICD10: C00-C96]
[1][2][3]
Chondrosarcoma
[ICD9: 170.9   ICD10: C41.9]
[4]
Emphysema
[ICD9: 492   ICD10: J43]
[5]
Hormone-refractory Prostate cancer
[ICD9: 185   ICD10: C61]
[6][7]
Kaposi's Sarcoma
[ICD9: 176   ICD10: C46]
[6][7]
Lung Cancer
[ICD9: 162   ICD10: C33-C34]
[8][9][10]
Myocardial infarction (MI)
[ICD9: 410   ICD10: I21, I22]
[11]
Non-small Cell Lung Cancer
[ICD9: 162   ICD10: C33, C34]
[6][7]
Osteoarthritis
[ICD9: 715   ICD10: M15-M19, M47]
[11]
Pancreatic Cancer
[ICD9: 157   ICD10: C25]
[8][9][10]
Drug(s)BB-3644Discontinued in Phase ICancer/Tumors[12][3]
BMS 275291Discontinued in Phase IIINon-small Cell Lung Cancer, Hormone-refractory Prostate Cancer, Kaposi's Sarcoma[6][7][13][12]
BatimastatDiscontinued in Phase ICancers[12]
MarimastatDiscontinued in Phase IIIPancreatic Cancer, Lung Cancer[14][9][10][12]
PrinomastatDiscontinued in Phase IIIBrain Cancer[15][16][17][18][12]
PrinomastatTrial haltedLung Cancer, Prostate Cancer[15][16][17][18][12]
XL784Discontinued in Phase IIDiabetic nephropathy[19]
BioChemical ClassHydrolases acting on peptide bonds (Peptidases)    
EC NumberEC 3.4.24.7
PathwayBladder cancer
PPAR signaling pathway
Pathways in cancer
UniProt IDP03956
PDB Structure1AYK; 1CGE; 1CGF; 1CGL; 1HFC; 1SU3; 2AYK; 2CLT; 2J0T; 2TCL; 3AYK; 3SHI; 4AUO; 4AYK; 966C.    
FunctionCleaves collagens of types i, ii, and iii at one site in the helical domain. Also cleaves collagens of types vii and x.    
SequenceMHSFPPLLLLLFWGVVSHSFPATLETQEQDVDLVQKYLEKYYNLKNDGRQVEKRRNSGPV VEKLKQMQEFFGLKVTGKPDAETLKVMKQPRCGVPDVAQFVLTEGNPRWEQTHLTYRIEN YTPDLPRADVDHAIEKAFQLWSNVTPLTFTKVSEGQADIMISFVRGDHRDNSPFDGPGGN LAHAFQPGPGIGGDAHFDEDERWTNNFREYNLHRVAAHELGHSLGLSHSTDIGALMYPSY TFSGDVQLAQDDIDGIQAIYGRSQNPVQPIGPQTPKACDSKLTFDAITTIRGEVMFFKDR FYMRTNPFYPEVELNFISVFWPQLPNGLEAAYEFADRDEVRFFKGNKYWAVQGQNVLHGY PKDIYSSFGFPRTVKHIDAALSEENTGKTYFFVANKYWRYDEYKRSMDPGYPKMIAHDFP GIGHKVDAVFMKDGFFYFFHGTRQYKFDPKTKRILTLQKANSWFNCRKN
Related US Patent6,608,112
Target ValidationClick to Find Target Validation Information.    
QSAR ModelClick to Find Target QSAR Model.    
Inhibitor3- (4-Methoxy-benzenesulfonyl)-cyclohexanethiol[20]
3- (4-Methoxy-benzenesulfonyl)-hexane-1-thiol[21]
3- (4-Methoxy-benzenesulfonyl)-pentane-1-thiol[21]
3- (4-Phenoxy-benzenesulfonyl)-cyclohexanethiol[20]
3- (4-Phenoxy-benzenesulfonyl)-propane-1-thiol[21]
3-Benzenesulfinyl-heptanoic acid hydroxyamide[22]
3-Benzenesulfonyl-heptanoic acid hydroxyamide[22]
3-Cyclohexanesulfonyl-heptanoic acid hydroxyamide[22]
4- (4-Butoxy-phenyl)-N-hydroxy-4-oxo-butyramide[23]
4- (4-Methoxy-benzenesulfonyl)-butane-2-thiol[21]
4-Butoxy-N-hydroxycarbamoylmethyl-benzamide[23]
BB-1101[24]
BB-3644[12][3]
BMS 275291[6][7][13][12]
Batimastat[12]
CGS-27023A[25]
CIPEMASTAT[26]
ILOMASTAT[27]
L-696418[28]
METHYLAMINO-PHENYLALANYL-LEUCYL-HYDROXAMIC ACID[29]
Marimastat[14][9][10][12]
N- (Ethylphosphoryl)-L-isoleucyl-L-Trp-NHCH3[30]
N-Hydroxy-4- (4-methoxy-phenyl)-4-oxo-butyramide[23]
N-Hydroxy-4-oxo-4- (4-phenoxy-phenyl)-butyramide[23]
N-Hydroxycarbamoylmethyl-4-methoxy-benzamide[23]
N-Hydroxycarbamoylmethyl-4-phenoxy-benzamide[23]
PKF-242-484,   TNF-484[26]
Prinomastat[15][16][17][18][12]
RO-319790[31]
RS-130830[32]
RS-39066[33]
Ro-31-4724[34]
Ro-32-3555[35]
Ro-37-9790[35]
SC-44463[36]
SR-973[37]
TMI-05[38]
XL784[19]
MultitargetBB-3644[12][3]
BMS 275291[6][7][13][12]
Batimastat[12]
Marimastat[14][9][10][12]
Prinomastat[15][16][17][18][12]
Cross References 3D Structure
Related Literature
On-Line Medical Dictionary
Ref 1Curr Pharm Des. 2005;11(3):295-322.Recent developments in the design of specific Matrix Metalloproteinase inhibitors aided by structural and computational studies. To Reference
Ref 2Metalloproteinase inhibition augments antitumor efficacy of the anti-CD30 immunotoxin Ki-3(scFv)-ETA' against human lymphomas in vivo. Int J Cancer. 2004 Sep 10;111(4):568-74. To Reference
Ref 3A 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 4Inhibition of MMP-1 expression by antisense RNA decreases invasiveness of human chondrosarcoma. J Orthop Res. 2003 Nov;21(6):1063-70. To Reference
Ref 5Extracellular regulated kinase/mitogen activated protein kinase is up-regulated in pulmonary emphysema and mediates matrix metalloproteinase-1 induction by cigarette smoke. J Biol Chem. 2004 Apr 23;279(17):17690-6. Epub 2004 Feb 5. To Reference
Ref 6Phase 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 7Randomized 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 8Novel investigational drugs for gastric cancer. Expert Opin Investig Drugs. 2009 Jul;18(7):945-55. To Reference
Ref 9Matrix metalloproteinase-2 involvement in breast cancer progression: a mini-review. Med Sci Monit. 2009 Feb;15(2):RA32-40. To Reference
Ref 10Matrix 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 11Am 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 1216498445 To Reference
Ref 13Randomized 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 14Metalloelastase (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 15AG-3340 (Agouron Pharmaceuticals Inc). IDrugs. 2000 Mar;3(3):336-45. To Reference
Ref 16Inhibition 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 17Delayed 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 18Pharmacoproteomics 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 19Agents in development for the treatment of diabetic nephropathy. Expert Opin Emerg Drugs. 2008 Sep;13(3):447-63. To Reference
Ref 20Bioorg Med Chem Lett. 1999 Jul 5;9(13):1757-60.Synthesis and identification of conformationally constrained selective MMP inhibitors. To Reference
Ref 21Bioorg Med Chem Lett. 1999 Apr 5;9(7):943-8.Discovery of a novel series of selective MMP inhibitors: identification of the gamma-sulfone-thiols. To Reference
Ref 22J Med Chem. 2000 Jun 15;43(12):2324-31.Hydroxamic acid derivatives as potent peptide deformylase inhibitors and antibacterial agents. To Reference
Ref 23J Med Chem. 2005 Oct 20;48(21):6585-96.Receptor flexibility in de novo ligand design and docking. To Reference
Ref 24Bioorg 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 25Bioorg Med Chem Lett. 2006 Feb 15;16(4):964-8. Epub 2005 Dec 9.The discovery of a potent and selective lethal factor inhibitor for adjunct therapy of anthrax infection. To Reference
Ref 26Bioorg Med Chem Lett. 2006 May 15;16(10):2632-6. Epub 2006 Mar 3.A cassette-dosing approach for improvement of oral bioavailability of dual TACE/MMP inhibitors. To Reference
Ref 27Bioorg 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 28Bioorg. Med. Chem. Lett. 5(6):539-542 (1995) To Reference
Ref 29Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. To Reference
Ref 30J Med Chem. 1990 Jan;33(1):263-73.Phosphoramidate peptide inhibitors of human skin fibroblast collagenase. To Reference
Ref 31Bioorg 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 32Bioorg 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 33Bioorg. Med. Chem. Lett. 6(13):1601-1606 (1996) To Reference
Ref 34J Med Chem. 2004 May 20;47(11):2761-7.Receptor flexibility in the in silico screening of reagents in the S1' pocket of human collagenase. To Reference
Ref 35Bioorg. Med. Chem. Lett. 7(17):2299-2302 (1997) To Reference
Ref 36J 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 37Bioorg 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 38Bioorg Med Chem Lett. 2006 Mar 15;16(6):1605-9. Epub 2006 Jan 19.Acetylenic TACE inhibitors. Part 3: Thiomorpholine sulfonamide hydroxamates. To Reference



 

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National University of Singapore, Singapore


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