Target Information
Target General Infomation | |||||
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Target ID |
T34296
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Former ID |
TTDC00150
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Target Name |
Collagenase 3
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Gene Name |
MMP13
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Synonyms |
Collagenase-3; MMP-13; Matrix metalloproteinase 13; Matrix metalloproteinase-13; MMP13
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Target Type |
Clinical Trial
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Disease | Cancer [ICD9: 140-229; ICD10: C00-C96] | ||||
HCV infection [ICD9: 070.4, 070.5, 070.70; ICD10: B17.1, B18.2] | |||||
Inflammatory disease [ICD9: 140-229, 147, 173, 573.3, 710-719; ICD10: C11, C44, K75.9, M00-M25] | |||||
Osteoarthritis [ICD9: 715; ICD10: M15-M19, M47] | |||||
Pain [ICD9: 338, 356.0, 356.8,780; ICD10: G64, G90.0, R52, G89] | |||||
Rheumatoid arthritis [ICD9: 710-719, 714; ICD10: M05-M06] | |||||
Function |
Plays a role in the degradation of extracellular matrix proteins including fibrillar collagen, fibronectin, TNC and ACAN. Cleaves triple helical collagens, including type I, type II and type III collagen, but has the highest activity with soluble type II collagen. Can also degrade collagen type IV, type XIV and type X. May also function by activating or degrading key regulatory proteins, such as TGFB1 and CTGF. Plays a role in wound healing, tissue remodeling, cartilage degradation, bone development, bone mineralization and ossification. Required for normal embryonic bone development and ossification. Plays a role in the healing of bone fractures via endochondral ossification. Plays a role in wound healing, probably by a mechanism that involves proteolytic activation of TGFB1 and degradation of CTGF. Plays a role in keratinocyte migration during wound healing. May play a role in cell migration and in tumor cell invasion.
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BioChemical Class |
Peptidase
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Target Validation |
T34296
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UniProt ID | |||||
EC Number |
EC 3.4.24.-
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Sequence |
MHPGVLAAFLFLSWTHCRALPLPSGGDEDDLSEEDLQFAERYLRSYYHPTNLAGILKENA
ASSMTERLREMQSFFGLEVTGKLDDNTLDVMKKPRCGVPDVGEYNVFPRTLKWSKMNLTY RIVNYTPDMTHSEVEKAFKKAFKVWSDVTPLNFTRLHDGIADIMISFGIKEHGDFYPFDG PSGLLAHAFPPGPNYGGDAHFDDDETWTSSSKGYNLFLVAAHEFGHSLGLDHSKDPGALM FPIYTYTGKSHFMLPDDDVQGIQSLYGPGDEDPNPKHPKTPDKCDPSLSLDAITSLRGET MIFKDRFFWRLHPQQVDAELFLTKSFWPELPNRIDAAYEHPSHDLIFIFRGRKFWALNGY DILEGYPKKISELGLPKEVKKISAAVHFEDTGKTLLFSGNQVWRYDDTNHIMDKDYPRLI EEDFPGIGDKVDAVYEKNGYIYFFNGPIQFEYSIWSNRIVRVMPANSILWC |
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Drugs and Mode of Action | |||||
Drug(s) | Curcumin | Drug Info | Phase 3 | Cancer | [532348], [542031] |
Apratastat | Drug Info | Phase 2 | Rheumatoid arthritis | [521616], [541616] | |
compound 1 | Drug Info | Clinical trial | Pain | [529099], [541654] | |
ILOMASTAT | Drug Info | Preclinical | Discovery agent | [542432], [544872] | |
RS-130830 | Drug Info | Discontinued in Phase 2 | HCV infection | [546851] | |
Inhibitor | (+/-)5-(biphenyl-4-yl)-3-hydroxypentanoic acid | Drug Info | [530333] | ||
1-(4-Methoxy-benzenesulfonyl)-heptane-3-thiol | Drug Info | [525485] | |||
1-Methyloxy-4-Sulfone-Benzene | Drug Info | [551393] | |||
2-(2-(biphenyl-4-yl)ethylsulfonyl)acetic acid | Drug Info | [530333] | |||
2-(4-methoxybenzylthio)-6-methylpyrimidin-4-ol | Drug Info | [529392] | |||
2-(biphenyl-4-ylsulfonamido)pentanedioic acid | Drug Info | [529392] | |||
2-(Biphenyl-4-ylsulfonyl)N-hydroxybenzamide | Drug Info | [530402] | |||
3-(4-Methoxy-benzenesulfonyl)-cyclohexanethiol | Drug Info | [525535] | |||
3-(4-Methoxy-benzenesulfonyl)-cyclopentanethiol | 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-Methoxy-benzenesulfonyl)-propane-1-thiol | Drug Info | [525485] | |||
3-(4-Phenoxy-benzenesulfonyl)-cyclohexanethiol | Drug Info | [525535] | |||
3-(4-Phenoxy-benzenesulfonyl)-propane-1-thiol | Drug Info | [525485] | |||
3-Benzenesulfonyl-heptanoic acid hydroxyamide | Drug Info | [525813] | |||
3-Cyclohexanesulfonyl-heptanoic acid hydroxyamide | Drug Info | [525813] | |||
3-Methylpyridine | Drug Info | [551393] | |||
4-(2,2'-bithiophen-5-ylmethyleneamino)phenol | Drug Info | [529388] | |||
4-(4-Methoxy-benzenesulfonyl)-butane-2-thiol | Drug Info | [525485] | |||
4-(methyl(4-phenylthiazol-2-yl)amino)phenol | Drug Info | [529388] | |||
4-amino-3-(4-(hexyloxy)phenyl)-4-oxobutanoic acid | Drug Info | [529392] | |||
5-(4'-cyanobiphenyl-4-yl)-3-hydroxypentanoic acid | Drug Info | [530333] | |||
CL82198 | Drug Info | [543454] | |||
compound 1 | Drug Info | [529099] | |||
compound 15 | Drug Info | [531667] | |||
Curcumin | Drug Info | [529388] | |||
Ethyl 2-cyano-2-(quinoxalin-2(1H)-ylidene)acetate | Drug Info | [529388] | |||
Hydroxyaminovaline | Drug Info | [551393] | |||
IK-682 | Drug Info | [526446] | |||
ILOMASTAT | Drug Info | [528945] | |||
MMI270 | Drug Info | [526039] | |||
MMP-13 inhibitors | Drug Info | [528284], [536172] | |||
MMP-13 inhibitors | Drug Info | [528284], [536172] | |||
N-Hydroxy-2-(4-phenoxy-benzenesulfonyl)benzamide | Drug Info | [530402] | |||
N1,N3-bis(3-methoxybenzyl)isophthalamide | Drug Info | [530571] | |||
N4,N6-dibenzylpyrimidine-4,6-dicarboxamide | Drug Info | [529830] | |||
PD-156 | Drug Info | [528284], [536172] | |||
PKF-242-484 | Drug Info | [528065] | |||
Ro-37-9790 | Drug Info | [551326] | |||
RS-130830 | Drug Info | [527412] | |||
SL422 | Drug Info | [526113] | |||
SR-973 | Drug Info | [528025] | |||
TMI-05 | Drug Info | [527982] | |||
UK-356618 | Drug Info | [526680] | |||
WAY-151693 | Drug Info | [551393] | |||
WAY170523 | Drug Info | [543454] | |||
[2-(Biphenyl-4-sulfonyl)phenyl]acetic Acid | Drug Info | [530402] | |||
Modulator | Apratastat | Drug Info | [528532], [536688] | ||
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
TEP | EXP Info | ||||
Pathways | |||||
NetPath Pathway | IL1 Signaling Pathway | ||||
PANTHER Pathway | Alzheimer disease-presenilin pathway | ||||
Plasminogen activating cascade | |||||
Pathway Interaction Database | Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling | ||||
Reactome | Collagen degradation | ||||
Degradation of the extracellular matrix | |||||
Activation of Matrix Metalloproteinases | |||||
Assembly of collagen fibrils and other multimeric structures | |||||
WikiPathways | Endochondral Ossification | ||||
Activation of Matrix Metalloproteinases | |||||
Oncostatin M Signaling Pathway | |||||
AGE/RAGE pathway | |||||
Matrix Metalloproteinases | |||||
References | |||||
Ref 521616 | ClinicalTrials.gov (NCT00095342) Study Evaluating TMI-005 in Active Rheumatoid Arthritis. U.S. National Institutes of Health. | ||||
Ref 529099 | Potent, selective spiropyrrolidine pyrimidinetrione inhibitors of MMP-13. Bioorg Med Chem Lett. 2007 Dec 1;17(23):6529-34. Epub 2007 Sep 29. | ||||
Ref 532348 | Nanocurcumin: a promising therapeutic advancement over native curcumin. Crit Rev Ther Drug Carrier Syst. 2013;30(4):331-68. | ||||
Ref 541616 | (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 541654 | (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: 6526). | ||||
Ref 542031 | (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: 7000). | ||||
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 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 526039 | Bioorg Med Chem Lett. 2001 Apr 23;11(8):1009-13.Heterocycle-based MMP inhibitors with P2' substituents. | ||||
Ref 526113 | Design, synthesis, and structure-activity relationships of macrocyclic hydroxamic acids that inhibit tumor necrosis factor alpha release in vitro and in vivo. J Med Chem. 2001 Aug 2;44(16):2636-60. | ||||
Ref 526446 | J 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. | ||||
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 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 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 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 528284 | Effects of selective matrix metalloproteinase inhibitor (PG-116800) to prevent ventricular remodeling after myocardial infarction: results of the PREMIER (Prevention of Myocardial Infarction Early Remodeling) trial. J Am Coll Cardiol. 2006 Jul 4;48(1):15-20. Epub 2006 Jun 21. | ||||
Ref 528532 | Drug evaluation: apratastat, a novel TACE/MMP inhibitor for rheumatoid arthritis. Curr Opin Investig Drugs. 2006 Nov;7(11):1014-9. | ||||
Ref 528945 | J Biol Chem. 2007 Sep 21;282(38):27781-91. Epub 2007 Jul 10.Discovery and characterization of a novel inhibitor of matrix metalloprotease-13 that reduces cartilage damage in vivo without joint fibroplasia side effects. | ||||
Ref 529099 | Potent, selective spiropyrrolidine pyrimidinetrione inhibitors of MMP-13. Bioorg Med Chem Lett. 2007 Dec 1;17(23):6529-34. Epub 2007 Sep 29. | ||||
Ref 529388 | Bioorg Med Chem. 2009 Feb 1;17(3):990-1005. Epub 2008 Mar 6.High throughput screening of potentially selective MMP-13 exosite inhibitors utilizing a triple-helical FRET substrate. | ||||
Ref 529392 | Bioorg Med Chem. 2009 Feb 1;17(3):1101-8. Epub 2008 Mar 8.Ranking the selectivity of PubChem screening hits by activity-based protein profiling: MMP13 as a case study. | ||||
Ref 529830 | Bioorg Med Chem Lett. 2009 Jan 1;19(1):47-50. Epub 2008 Nov 18.Calculation of binding free energies for non-zinc chelating pyrimidine dicarboxamide inhibitors with MMP-13. | ||||
Ref 530333 | Bioorg 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. | ||||
Ref 530402 | J 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. | ||||
Ref 530571 | Bioorg Med Chem Lett. 2010 Jan 15;20(2):576-80. Epub 2009 Nov 22.Discovery of (pyridin-4-yl)-2H-tetrazole as a novel scaffold to identify highly selective matrix metalloproteinase-13 inhibitors for the treatment of osteoarthritis. | ||||
Ref 531667 | Fragment-based discovery of indole inhibitors of matrix metalloproteinase-13. J Med Chem. 2011 Dec 8;54(23):8174-87. | ||||
Ref 536172 | Selective matrix metalloproteinase inhibition attenuates progression of left ventricular dysfunction and remodeling in dogs with chronic heart failure. Am J Physiol Heart Circ Physiol. 2006 Jun;290(6):H2522-7. Epub 2006 Jan 20. | ||||
Ref 536688 | Drug insight: tumor necrosis factor-converting enzyme as a pharmaceutical target for rheumatoid arthritis. Nat Clin Pract Rheumatol. 2008 Jun;4(6):300-9. Epub 2008 Apr 15. | ||||
Ref 543454 | (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. (Target id: 1637). |
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