Target Information
Target General Infomation | |||||
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Target ID |
T52450
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Former ID |
TTDC00147
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Target Name |
Interstitial collagenase
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Gene Name |
MMP1
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Synonyms |
Fibroblast collagenase; MMP-1; Matrix metalloproteinase-1; MMP1
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Target Type |
Successful
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Disease | Arthritis [ICD9: 710-719; ICD10: M00-M25] | ||||
Brain cancer [ICD9: 191, 225.0; ICD10: C71, D33] | |||||
Cancer [ICD9: 140-229; ICD10: C00-C96] | |||||
Diabetic nephropathy [ICD9: 250.4; ICD10: E11.21] | |||||
HCV infection [ICD9: 070.4, 070.5, 070.70; ICD10: B17.1, B18.2] | |||||
Lung cancer; Prostate cancer [ICD9: 140-229, 162, 185; ICD10: C33-C34, C61] | |||||
Multiple scierosis [ICD9: 340; ICD10: G35] | |||||
Non-small-cell lung cancer; Hormone-refractory prostate cancer; Kaposi's sarcoma [ICD9: 140-229, 162, 176, 185, 204.0; ICD10: C33, C33-C34, C34, C46, C61, C91.0] | |||||
Pancreatic cancer; Lung cancer [ICD9: 140-229, 157, 162; ICD10: C25, C33-C34] | |||||
Pancreatic cancer [ICD9: 140-199, 140-229, 157, 210-229; ICD10: C25] | |||||
Rheumatoid arthritis [ICD9: 710-719, 714; ICD10: M05-M06] | |||||
Function |
Cleaves collagens of types I, II, and III at one site in the helical domain. Also cleaves collagens of types VII and X. In case of HIV infection, interacts and cleaves the secreted viral Tat protein, leading to a decrease in neuronal Tat's mediated neurotoxicity.
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BioChemical Class |
Peptidase
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Target Validation |
T52450
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UniProt ID | |||||
EC Number |
EC 3.4.24.7
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Sequence |
MHSFPPLLLLLFWGVVSHSFPATLETQEQDVDLVQKYLEKYYNLKNDGRQVEKRRNSGPV
VEKLKQMQEFFGLKVTGKPDAETLKVMKQPRCGVPDVAQFVLTEGNPRWEQTHLTYRIEN YTPDLPRADVDHAIEKAFQLWSNVTPLTFTKVSEGQADIMISFVRGDHRDNSPFDGPGGN LAHAFQPGPGIGGDAHFDEDERWTNNFREYNLHRVAAHELGHSLGLSHSTDIGALMYPSY TFSGDVQLAQDDIDGIQAIYGRSQNPVQPIGPQTPKACDSKLTFDAITTIRGEVMFFKDR FYMRTNPFYPEVELNFISVFWPQLPNGLEAAYEFADRDEVRFFKGNKYWAVQGQNVLHGY PKDIYSSFGFPRTVKHIDAALSEENTGKTYFFVANKYWRYDEYKRSMDPGYPKMIAHDFP GIGHKVDAVFMKDGFFYFFHGTRQYKFDPKTKRILTLQKANSWFNCRKN |
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Drugs and Mode of Action | |||||
Drug(s) | Prinomastat | Drug Info | Approved | Lung cancer; Prostate cancer | [536056], [541642] |
CIPEMASTAT | Drug Info | Phase 3 | Rheumatoid arthritis | [532656], [541601] | |
Marimastat | Drug Info | Phase 3 | Pancreatic cancer | [468274], [527314] | |
ILOMASTAT | Drug Info | Preclinical | Discovery agent | [542432], [544872] | |
BMS 275291 | Drug Info | Discontinued in Phase 3 | Non-small-cell lung cancer; Hormone-refractory prostate cancer; Kaposi's sarcoma | [536608] | |
Marimastat | Drug Info | Discontinued in Phase 3 | Pancreatic cancer; Lung cancer | [468274], [536223] | |
Prinomastat | Drug Info | Discontinued in Phase 3 | Brain cancer | [536056], [541642] | |
RS-130830 | Drug Info | Discontinued in Phase 2 | HCV infection | [546851] | |
XL784 | Drug Info | Discontinued in Phase 2 | Diabetic nephropathy | [536836] | |
BB-1101 | Drug Info | Terminated | Multiple scierosis | [546101] | |
BB-3644 | Drug Info | Terminated | Cancer | [535909] | |
L-696418 | Drug Info | Terminated | Discovery agent | [546087] | |
Ro-31-4724 | Drug Info | Terminated | Arthritis | [534482] | |
RO-319790 | Drug Info | Terminated | Rheumatoid arthritis | [545173] | |
SC-44463 | Drug Info | Terminated | Discovery agent | [546364] | |
Inhibitor | 3-(4-Methoxy-benzenesulfonyl)-cyclohexanethiol | Drug Info | [525535] | ||
3-(4-Methoxy-benzenesulfonyl)-hexane-1-thiol | Drug Info | [525485] | |||
3-(4-Methoxy-benzenesulfonyl)-pentane-1-thiol | Drug Info | [525485] | |||
3-(4-Phenoxy-benzenesulfonyl)-cyclohexanethiol | Drug Info | [525535] | |||
3-(4-Phenoxy-benzenesulfonyl)-propane-1-thiol | Drug Info | [525485] | |||
3-Benzenesulfinyl-heptanoic acid hydroxyamide | Drug Info | [525813] | |||
3-Benzenesulfonyl-heptanoic acid hydroxyamide | Drug Info | [525813] | |||
3-Cyclohexanesulfonyl-heptanoic acid hydroxyamide | Drug Info | [525813] | |||
4-(4-Butoxy-phenyl)-N-hydroxy-4-oxo-butyramide | Drug Info | [527800] | |||
4-(4-Methoxy-benzenesulfonyl)-butane-2-thiol | Drug Info | [525485] | |||
4-Butoxy-N-hydroxycarbamoylmethyl-benzamide | Drug Info | [527800] | |||
BB-1101 | Drug Info | [534793] | |||
BB-3644 | Drug Info | [528049], [535909] | |||
BMS 275291 | Drug Info | [528049], [536019], [536073], [536608] | |||
ILOMASTAT | Drug Info | [529683] | |||
L-696418 | Drug Info | [551297] | |||
Marimastat | Drug Info | [528049], [536340], [537040], [538064] | |||
METHYLAMINO-PHENYLALANYL-LEUCYL-HYDROXAMIC ACID | Drug Info | [551374] | |||
MMI270 | Drug Info | [527922] | |||
N-(Ethylphosphoryl)-L-isoleucyl-L-Trp-NHCH3 | Drug Info | [531455] | |||
N-Hydroxy-4-(4-methoxy-phenyl)-4-oxo-butyramide | Drug Info | [527800] | |||
N-Hydroxy-4-oxo-4-(4-phenoxy-phenyl)-butyramide | Drug Info | [527800] | |||
N-Hydroxycarbamoylmethyl-4-methoxy-benzamide | Drug Info | [527800] | |||
N-Hydroxycarbamoylmethyl-4-phenoxy-benzamide | Drug Info | [527800] | |||
PKF-242-484 | Drug Info | [528065] | |||
Prinomastat | Drug Info | [528049], [536127], [536723], [536808], [537136] | |||
Ro-31-4724 | Drug Info | [527073] | |||
RO-319790 | Drug Info | [534791] | |||
Ro-37-9790 | Drug Info | [551326] | |||
RS-130830 | Drug Info | [527412] | |||
RS-39066 | Drug Info | [551301] | |||
SC-44463 | Drug Info | [526680] | |||
SR-973 | Drug Info | [528025] | |||
TMI-05 | Drug Info | [527982] | |||
XL784 | Drug Info | [536836] | |||
Modulator | CIPEMASTAT | Drug Info | [532656] | ||
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
TEP | EXP Info | ||||
Pathways | |||||
KEGG Pathway | PPAR signaling pathway | ||||
Pathways in cancer | |||||
Bladder cancer | |||||
Rheumatoid arthritis | |||||
NetPath Pathway | IL1 Signaling Pathway | ||||
EGFR1 Signaling Pathway | |||||
TWEAK Signaling Pathway | |||||
Wnt Signaling Pathway | |||||
PANTHER Pathway | Alzheimer disease-presenilin pathway | ||||
Plasminogen activating cascade | |||||
Pathway Interaction Database | Endothelins | ||||
Validated transcriptional targets of AP1 family members Fra1 and Fra2 | |||||
Glucocorticoid receptor regulatory network | |||||
AP-1 transcription factor network | |||||
Syndecan-1-mediated signaling events | |||||
Reactome | Collagen degradation | ||||
Degradation of the extracellular matrix | |||||
Activation of Matrix Metalloproteinases | |||||
Basigin interactions | |||||
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) | |||||
WikiPathways | TGF beta Signaling Pathway | ||||
Bladder Cancer | |||||
Activation of Matrix Metalloproteinases | |||||
Degradation of collagen | |||||
Quercetin and Nf-kB/ AP-1 Induced Cell Apoptosis | |||||
Oncostatin M Signaling Pathway | |||||
Prostate Cancer | |||||
Integrated Breast Cancer Pathway | |||||
Integrated Cancer pathway | |||||
Cell surface interactions at the vascular wall | |||||
Matrix Metalloproteinases | |||||
References | |||||
Ref 468274 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5220). | ||||
Ref 527314 | Randomized phase III trial of marimastat versus placebo in patients with metastatic breast cancer who have responding or stable disease after first-line chemotherapy: Eastern Cooperative Oncology Group trial E2196. J Clin Oncol. 2004 Dec 1;22(23):4683-90. | ||||
Ref 532656 | Matrix metalloproteinase inhibition lowers mortality and brain injury in experimental pneumococcal meningitis. Infect Immun. 2014 Apr;82(4):1710-8. | ||||
Ref 534482 | Effects of the hydroxamic acid derivate Ro 31-4724 on the metabolism and morphology of interleukin-1-treated cartilage explants. Pharmacology. 1997 Aug;55(2):95-108. | ||||
Ref 535909 | A 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. | ||||
Ref 536223 | Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91. | ||||
Ref 536608 | Phase 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. | ||||
Ref 536836 | Agents in development for the treatment of diabetic nephropathy. Expert Opin Emerg Drugs. 2008 Sep;13(3):447-63. | ||||
Ref 541601 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6466). | ||||
Ref 541642 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6505). | ||||
Ref 542432 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7409). | ||||
Ref 544872 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001387) | ||||
Ref 545173 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002350) | ||||
Ref 546087 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006282) | ||||
Ref 546101 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006361) | ||||
Ref 525485 | Bioorg 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. | ||||
Ref 525535 | Bioorg Med Chem Lett. 1999 Jul 5;9(13):1757-60.Synthesis and identification of conformationally constrained selective MMP inhibitors. | ||||
Ref 525813 | J Med Chem. 2000 Jun 15;43(12):2324-31.Hydroxamic acid derivatives as potent peptide deformylase inhibitors and antibacterial agents. | ||||
Ref 526680 | J 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. | ||||
Ref 527073 | J 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. | ||||
Ref 527412 | Bioorg Med Chem Lett. 2005 Feb 15;15(4):1101-6.Structure-based design of potent and selective inhibitors of collagenase-3 (MMP-13). | ||||
Ref 527800 | J Med Chem. 2005 Oct 20;48(21):6585-96.Receptor flexibility in de novo ligand design and docking. | ||||
Ref 527922 | Bioorg 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. | ||||
Ref 527982 | Bioorg Med Chem Lett. 2006 Mar 15;16(6):1605-9. Epub 2006 Jan 19.Acetylenic TACE inhibitors. Part 3: Thiomorpholine sulfonamide hydroxamates. | ||||
Ref 528025 | Bioorg Med Chem Lett. 2006 May 1;16(9):2357-63. Epub 2006 Feb 10.Synthesis and evaluation of succinoyl-caprolactam gamma-secretase inhibitors. | ||||
Ref 528049 | Tumour microenvironment - opinion: validating matrix metalloproteinases as drug targets and anti-targets for cancer therapy. Nat Rev Cancer. 2006 Mar;6(3):227-39. | ||||
Ref 528065 | Bioorg 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. | ||||
Ref 529683 | Bioorg 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. | ||||
Ref 531455 | J Med Chem. 1990 Jan;33(1):263-73.Phosphoramidate peptide inhibitors of human skin fibroblast collagenase. | ||||
Ref 532656 | Matrix metalloproteinase inhibition lowers mortality and brain injury in experimental pneumococcal meningitis. Infect Immun. 2014 Apr;82(4):1710-8. | ||||
Ref 534791 | Bioorg 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. | ||||
Ref 534793 | Bioorg 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. | ||||
Ref 535909 | A 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. | ||||
Ref 536019 | Randomized 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. | ||||
Ref 536073 | Randomized 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. | ||||
Ref 536340 | Metalloelastase (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. | ||||
Ref 536608 | Phase 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. | ||||
Ref 536723 | Pharmacoproteomics 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. | ||||
Ref 536808 | Delayed administration of a matrix metalloproteinase inhibitor limits progressive brain injury after hypoxia-ischemia in the neonatal rat. J Neuroinflammation. 2008 Aug 11;5:34. | ||||
Ref 536836 | Agents in development for the treatment of diabetic nephropathy. Expert Opin Emerg Drugs. 2008 Sep;13(3):447-63. | ||||
Ref 537040 | Matrix metalloproteinase-2 involvement in breast cancer progression: a mini-review. Med Sci Monit. 2009 Feb;15(2):RA32-40. | ||||
Ref 537136 | Inhibition 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. | ||||
Ref 538064 | Matrix metalloproteinase inhibition as a novel anticancer strategy: a review with special focus on batimastat and marimastat. Pharmacol Ther. 1997;75(1):69-75. | ||||
Ref 551297 | Inhibition of matrix metalloproteinases by N-carboxyalkyl peptides containing extended alkyl residues At P1', Bioorg. Med. Chem. Lett. 5(6):539-542 (1995). | ||||
Ref 551301 | Design, synthesis, activity, and structure of a novel class of matrix metalloproteinase inhibitors containing a heterocyclic P2??P3?? Bioorg. Med. Chem. Lett. 6(13):1541-1542 (1996). |
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