Target Information
| Target General Information | Top | |||||
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| Target ID |
T52450
(Former ID: TTDC00147)
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| Target Name |
Matrix metalloproteinase-1 (MMP-1)
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| Synonyms |
Interstitial collagenase; Fibroblast collagenase; CLG
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| Gene Name |
MMP1
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Lung cancer [ICD-11: 2C25] | |||||
| Function |
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. Cleaves collagens of types I, II, and III at one site in the helical domain.
Click to Show/Hide
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| BioChemical Class |
Peptidase
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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 Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T80OJF | |||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | Prinomastat | Drug Info | Approved | Lung cancer | [2], [3] | |
| Clinical Trial Drug(s) | [+] 3 Clinical Trial Drugs | + | ||||
| 1 | CIPEMASTAT | Drug Info | Phase 3 | Rheumatoid arthritis | [4], [5] | |
| 2 | Marimastat | Drug Info | Phase 3 | Pancreatic cancer | [6], [7] | |
| 3 | Apratastat | Drug Info | Phase 2 | Rheumatoid arthritis | [8], [9] | |
| Discontinued Drug(s) | [+] 8 Discontinued Drugs | + | ||||
| 1 | BMS 275291 | Drug Info | Discontinued in Phase 3 | Kaposi sarcoma | [10] | |
| 2 | GM6001 | Drug Info | Discontinued in Phase 2 | Corneal ulcer | [11] | |
| 3 | RS-130830 | Drug Info | Discontinued in Phase 2 | Hepatitis C virus infection | [12] | |
| 4 | XL784 | Drug Info | Discontinued in Phase 2 | Diabetic nephropathy | [13] | |
| 5 | BB-1101 | Drug Info | Terminated | Multiple sclerosis | [14] | |
| 6 | BB-3644 | Drug Info | Terminated | Solid tumour/cancer | [15] | |
| 7 | Ro-31-4724 | Drug Info | Terminated | Arthritis | [16] | |
| 8 | RO-319790 | Drug Info | Terminated | Rheumatoid arthritis | [17] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Inhibitor | [+] 37 Inhibitor drugs | + | ||||
| 1 | Prinomastat | Drug Info | [1], [18], [19], [20], [21] | |||
| 2 | Marimastat | Drug Info | [22], [23], [24], [21] | |||
| 3 | Apratastat | Drug Info | [25] | |||
| 4 | PMID29130358-Compound-Figure10(2a) | Drug Info | [26] | |||
| 5 | PMID29130358-Compound-Figure18(14a) | Drug Info | [26] | |||
| 6 | BMS 275291 | Drug Info | [10], [27], [28], [21] | |||
| 7 | GM6001 | Drug Info | [29] | |||
| 8 | RS-130830 | Drug Info | [30] | |||
| 9 | XL784 | Drug Info | [13] | |||
| 10 | BB-1101 | Drug Info | [31] | |||
| 11 | BB-3644 | Drug Info | [21], [15] | |||
| 12 | L-696418 | Drug Info | [32] | |||
| 13 | Ro-31-4724 | Drug Info | [33] | |||
| 14 | RO-319790 | Drug Info | [34] | |||
| 15 | SC-44463 | Drug Info | [35] | |||
| 16 | 3-(4-Methoxy-benzenesulfonyl)-cyclohexanethiol | Drug Info | [36] | |||
| 17 | 3-(4-Methoxy-benzenesulfonyl)-hexane-1-thiol | Drug Info | [37] | |||
| 18 | 3-(4-Methoxy-benzenesulfonyl)-pentane-1-thiol | Drug Info | [37] | |||
| 19 | 3-(4-Phenoxy-benzenesulfonyl)-cyclohexanethiol | Drug Info | [36] | |||
| 20 | 3-(4-Phenoxy-benzenesulfonyl)-propane-1-thiol | Drug Info | [37] | |||
| 21 | 3-Benzenesulfinyl-heptanoic acid hydroxyamide | Drug Info | [38] | |||
| 22 | 3-Benzenesulfonyl-heptanoic acid hydroxyamide | Drug Info | [38] | |||
| 23 | 3-Cyclohexanesulfonyl-heptanoic acid hydroxyamide | Drug Info | [38] | |||
| 24 | 4-(4-Butoxy-phenyl)-N-hydroxy-4-oxo-butyramide | Drug Info | [39] | |||
| 25 | 4-(4-Methoxy-benzenesulfonyl)-butane-2-thiol | Drug Info | [37] | |||
| 26 | 4-Butoxy-N-hydroxycarbamoylmethyl-benzamide | Drug Info | [39] | |||
| 27 | METHYLAMINO-PHENYLALANYL-LEUCYL-HYDROXAMIC ACID | Drug Info | [40] | |||
| 28 | MMI270 | Drug Info | [41] | |||
| 29 | N-(Ethylphosphoryl)-L-isoleucyl-L-Trp-NHCH3 | Drug Info | [42] | |||
| 30 | N-Hydroxy-4-(4-methoxy-phenyl)-4-oxo-butyramide | Drug Info | [39] | |||
| 31 | N-Hydroxy-4-oxo-4-(4-phenoxy-phenyl)-butyramide | Drug Info | [39] | |||
| 32 | N-Hydroxycarbamoylmethyl-4-methoxy-benzamide | Drug Info | [39] | |||
| 33 | N-Hydroxycarbamoylmethyl-4-phenoxy-benzamide | Drug Info | [39] | |||
| 34 | PKF-242-484 | Drug Info | [43] | |||
| 35 | Ro-37-9790 | Drug Info | [44] | |||
| 36 | RS-39066 | Drug Info | [45] | |||
| 37 | SR-973 | Drug Info | [46] | |||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | CIPEMASTAT | Drug Info | [5] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target-regulating Transcription Factors | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| Target QSAR Model | ||||||
| References | Top | |||||
|---|---|---|---|---|---|---|
| REF 1 | AG-3340 (Agouron Pharmaceuticals Inc). IDrugs. 2000 Mar;3(3):336-45. | |||||
| REF 2 | URL: 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 3 | Emerging therapies for neuropathic pain. Expert Opin Emerg Drugs. 2005 Feb;10(1):95-108. | |||||
| REF 4 | URL: 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 5 | Matrix metalloproteinase inhibition lowers mortality and brain injury in experimental pneumococcal meningitis. Infect Immun. 2014 Apr;82(4):1710-8. | |||||
| REF 6 | URL: 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 7 | 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 8 | URL: 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: 6482). | |||||
| REF 9 | ClinicalTrials.gov (NCT00095342) Study Evaluating TMI-005 in Active Rheumatoid Arthritis. U.S. National Institutes of Health. | |||||
| REF 10 | 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 11 | 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 12 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010620) | |||||
| REF 13 | Agents in development for the treatment of diabetic nephropathy. Expert Opin Emerg Drugs. 2008 Sep;13(3):447-63. | |||||
| REF 14 | 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 15 | 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 16 | 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 17 | 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 18 | Inhibition of gelatinase activity reduces neural injury in an ex vivo model of hypoxia-ischemia. Neuroscience. 2009 Jun 2;160(4):755-66. | |||||
| REF 19 | 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 20 | Pharmacoproteomics of a metalloproteinase hydroxamate inhibitor in breast cancer cells: dynamics of membrane type 1 matrix metalloproteinase-mediat... Mol Cell Biol. 2008 Aug;28(15):4896-914. | |||||
| REF 21 | 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 22 | 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. | |||||
| REF 23 | Matrix metalloproteinase-2 involvement in breast cancer progression: a mini-review. Med Sci Monit. 2009 Feb;15(2):RA32-40. | |||||
| REF 24 | 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 25 | Acetylenic TACE inhibitors. Part 3: Thiomorpholine sulfonamide hydroxamates. Bioorg Med Chem Lett. 2006 Mar 15;16(6):1605-9. | |||||
| REF 26 | Gelatinase inhibitors: a patent review (2011-2017).Expert Opin Ther Pat. 2018 Jan;28(1):31-46. | |||||
| REF 27 | 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 28 | 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 29 | Introduction of the 4-(4-bromophenyl)benzenesulfonyl group to hydrazide analogs of Ilomastat leads to potent gelatinase B (MMP-9) inhibitors with i... Bioorg Med Chem. 2008 Sep 15;16(18):8745-59. | |||||
| REF 30 | Structure-based design of potent and selective inhibitors of collagenase-3 (MMP-13). Bioorg Med Chem Lett. 2005 Feb 15;15(4):1101-6. | |||||
| REF 31 | Broad spectrum matrix metalloproteinase inhibitors: an examination of succinamide hydroxamate inhibitors with P1 C alpha gem-disubstitution. Bioorg Med Chem Lett. 1998 Jun 16;8(12):1443-8. | |||||
| REF 32 | Inhibition of matrix metalloproteinases by N-carboxyalkyl peptides containing extended alkyl residues At P1', Bioorg. Med. Chem. Lett. 5(6):539-542 (1995). | |||||
| REF 33 | Receptor flexibility in the in silico screening of reagents in the S1' pocket of human collagenase. J Med Chem. 2004 May 20;47(11):2761-7. | |||||
| REF 34 | The asymmetric synthesis and in vitro characterization of succinyl mercaptoalcohol and mercaptoketone inhibitors of matrix metalloproteinases. Bioorg Med Chem Lett. 1998 May 19;8(10):1163-8. | |||||
| REF 35 | A potent, selective inhibitor of matrix metalloproteinase-3 for the topical treatment of chronic dermal ulcers. J Med Chem. 2003 Jul 31;46(16):3514-25. | |||||
| REF 36 | Synthesis and identification of conformationally constrained selective MMP inhibitors. Bioorg Med Chem Lett. 1999 Jul 5;9(13):1757-60. | |||||
| REF 37 | Discovery of a novel series of selective MMP inhibitors: identification of the gamma-sulfone-thiols. Bioorg Med Chem Lett. 1999 Apr 5;9(7):943-8. | |||||
| REF 38 | Hydroxamic acid derivatives as potent peptide deformylase inhibitors and antibacterial agents. J Med Chem. 2000 Jun 15;43(12):2324-31. | |||||
| REF 39 | Receptor flexibility in de novo ligand design and docking. J Med Chem. 2005 Oct 20;48(21):6585-96. | |||||
| REF 40 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
| REF 41 | The discovery of a potent and selective lethal factor inhibitor for adjunct therapy of anthrax infection. Bioorg Med Chem Lett. 2006 Feb 15;16(4):964-8. | |||||
| REF 42 | Phosphoramidate peptide inhibitors of human skin fibroblast collagenase. J Med Chem. 1990 Jan;33(1):263-73. | |||||
| REF 43 | A cassette-dosing approach for improvement of oral bioavailability of dual TACE/MMP inhibitors. Bioorg Med Chem Lett. 2006 May 15;16(10):2632-6. | |||||
| REF 44 | 11,21-Bisphenyl-19-norpregnane derivatives are selective antiglucocorticoids, Bioorg. Med. Chem. Lett. 7(17):2299-2302 (1997). | |||||
| REF 45 | 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). | |||||
| REF 46 | Synthesis and evaluation of succinoyl-caprolactam gamma-secretase inhibitors. Bioorg Med Chem Lett. 2006 May 1;16(9):2357-63. | |||||
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