Target General Infomation
Target ID
T52450
Former ID
TTDC00147
Target Name
Interstitial collagenase
Gene Name
MMP1
Synonyms
Fibroblast collagenase; MMP-1; Matrix metalloproteinase-1; MMP1
Target Type
Successful
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.
BioChemical Class
Peptidase
Target Validation
T52450
UniProt ID
EC Number
EC 3.4.24.7
Sequence
MHSFPPLLLLLFWGVVSHSFPATLETQEQDVDLVQKYLEKYYNLKNDGRQVEKRRNSGPV
VEKLKQMQEFFGLKVTGKPDAETLKVMKQPRCGVPDVAQFVLTEGNPRWEQTHLTYRIEN
YTPDLPRADVDHAIEKAFQLWSNVTPLTFTKVSEGQADIMISFVRGDHRDNSPFDGPGGN
LAHAFQPGPGIGGDAHFDEDERWTNNFREYNLHRVAAHELGHSLGLSHSTDIGALMYPSY
TFSGDVQLAQDDIDGIQAIYGRSQNPVQPIGPQTPKACDSKLTFDAITTIRGEVMFFKDR
FYMRTNPFYPEVELNFISVFWPQLPNGLEAAYEFADRDEVRFFKGNKYWAVQGQNVLHGY
PKDIYSSFGFPRTVKHIDAALSEENTGKTYFFVANKYWRYDEYKRSMDPGYPKMIAHDFP
GIGHKVDAVFMKDGFFYFFHGTRQYKFDPKTKRILTLQKANSWFNCRKN
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 527314Randomized 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 532656Matrix metalloproteinase inhibition lowers mortality and brain injury in experimental pneumococcal meningitis. Infect Immun. 2014 Apr;82(4):1710-8.
Ref 534482Effects 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 535909A 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 536056Emerging therapies for neuropathic pain. Expert Opin Emerg Drugs. 2005 Feb;10(1):95-108.
Ref 536223Emerging drugs for the treatment of chronic obstructive pulmonary disease. Expert Opin Emerg Drugs. 2006 May;11(2):275-91.
Ref 536608Phase 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 536836Agents 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 544872Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001387)
Ref 545173Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002350)
Ref 546087Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006282)
Ref 546101Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006361)
Ref 546364Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007717)
Ref 546851Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010620)
Ref 525485Bioorg 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 525535Bioorg Med Chem Lett. 1999 Jul 5;9(13):1757-60.Synthesis and identification of conformationally constrained selective MMP inhibitors.
Ref 525813J Med Chem. 2000 Jun 15;43(12):2324-31.Hydroxamic acid derivatives as potent peptide deformylase inhibitors and antibacterial agents.
Ref 526680J 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 527073J 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 527412Bioorg Med Chem Lett. 2005 Feb 15;15(4):1101-6.Structure-based design of potent and selective inhibitors of collagenase-3 (MMP-13).
Ref 527800J Med Chem. 2005 Oct 20;48(21):6585-96.Receptor flexibility in de novo ligand design and docking.
Ref 527922Bioorg 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 527982Bioorg Med Chem Lett. 2006 Mar 15;16(6):1605-9. Epub 2006 Jan 19.Acetylenic TACE inhibitors. Part 3: Thiomorpholine sulfonamide hydroxamates.
Ref 528025Bioorg Med Chem Lett. 2006 May 1;16(9):2357-63. Epub 2006 Feb 10.Synthesis and evaluation of succinoyl-caprolactam gamma-secretase inhibitors.
Ref 528049Tumour microenvironment - opinion: validating matrix metalloproteinases as drug targets and anti-targets for cancer therapy. Nat Rev Cancer. 2006 Mar;6(3):227-39.
Ref 528065Bioorg 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 529683Bioorg 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 531455J Med Chem. 1990 Jan;33(1):263-73.Phosphoramidate peptide inhibitors of human skin fibroblast collagenase.
Ref 532656Matrix metalloproteinase inhibition lowers mortality and brain injury in experimental pneumococcal meningitis. Infect Immun. 2014 Apr;82(4):1710-8.
Ref 534791Bioorg 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 534793Bioorg 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 535909A 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 536019Randomized 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 536073Randomized 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 536127AG-3340 (Agouron Pharmaceuticals Inc). IDrugs. 2000 Mar;3(3):336-45.
Ref 536340Metalloelastase (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 536608Phase 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 536723Pharmacoproteomics 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 536808Delayed 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 536836Agents in development for the treatment of diabetic nephropathy. Expert Opin Emerg Drugs. 2008 Sep;13(3):447-63.
Ref 537040Matrix metalloproteinase-2 involvement in breast cancer progression: a mini-review. Med Sci Monit. 2009 Feb;15(2):RA32-40.
Ref 537136Inhibition 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 538064Matrix metalloproteinase inhibition as a novel anticancer strategy: a review with special focus on batimastat and marimastat. Pharmacol Ther. 1997;75(1):69-75.
Ref 551297Inhibition of matrix metalloproteinases by N-carboxyalkyl peptides containing extended alkyl residues At P1', Bioorg. Med. Chem. Lett. 5(6):539-542 (1995).
Ref 551301Design, 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 55132611,21-Bisphenyl-19-norpregnane derivatives are selective antiglucocorticoids, Bioorg. Med. Chem. Lett. 7(17):2299-2302 (1997).
Ref 551374The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
Ref 1587926URL: https://www.ebi.ac.uk/chembl/ The ChEMBL database in 2017

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