Target Information
Target General Infomation | |||||
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Target ID |
T68251
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Former ID |
TTDC00104
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Target Name |
72 kDa type IV collagenase
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Gene Name |
MMP2
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Synonyms |
72 kDa gelatinase; Gelatinase A; MMP-2; Matrix metalloproteinase 2; Matrix metalloproteinase-2; TBE-1; MMP2
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Target Type |
Successful
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Disease | Acne vulgaris [ICD9: 706.1; ICD10: L70.0] | ||||
Brain cancer [ICD9: 191, 225.0; ICD10: C71, D33] | |||||
Cancer [ICD9: 140-229; ICD10: C00-C96] | |||||
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; Renal cell carcinoma [ICD9: 140-229, 162, 162.9, 189, 204.0; ICD10: C33, C33-C34, C34, C34.90, C64, C91.0] | |||||
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; Ovarian cancer; Osteoarthritis [ICD9: 140-229, 157, 162, 183, 715; ICD10: C25, C33-C34, C56, M15-M19, M47] | |||||
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] | |||||
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48] | |||||
Function |
Isoform 2: Mediates the proteolysis of CHUK/IKKA and initiates a primary innate immune response by inducing mitochondrial-nuclear stress signaling with activation of the pro- inflammatory NF-kappaB, NFAT and IRF transcriptional pathways.
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BioChemical Class |
Peptidase
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Target Validation |
T68251
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UniProt ID | |||||
EC Number |
EC 3.4.24.24
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Sequence |
MEALMARGALTGPLRALCLLGCLLSHAAAAPSPIIKFPGDVAPKTDKELAVQYLNTFYGC
PKESCNLFVLKDTLKKMQKFFGLPQTGDLDQNTIETMRKPRCGNPDVANYNFFPRKPKWD KNQITYRIIGYTPDLDPETVDDAFARAFQVWSDVTPLRFSRIHDGEADIMINFGRWEHGD GYPFDGKDGLLAHAFAPGTGVGGDSHFDDDELWTLGEGQVVRVKYGNADGEYCKFPFLFN GKEYNSCTDTGRSDGFLWCSTTYNFEKDGKYGFCPHEALFTMGGNAEGQPCKFPFRFQGT SYDSCTTEGRTDGYRWCGTTEDYDRDKKYGFCPETAMSTVGGNSEGAPCVFPFTFLGNKY ESCTSAGRSDGKMWCATTANYDDDRKWGFCPDQGYSLFLVAAHEFGHAMGLEHSQDPGAL MAPIYTYTKNFRLSQDDIKGIQELYGASPDIDLGTGPTPTLGPVTPEICKQDIVFDGIAQ IRGEIFFFKDRFIWRTVTPRDKPMGPLLVATFWPELPEKIDAVYEAPQEEKAVFFAGNEY WIYSASTLERGYPKPLTSLGLPPDVQRVDAAFNWSKNKKTYIFAGDKFWRYNEVKKKMDP GFPKLIADAWNAIPDNLDAVVDLQGGGHSYFFKGAYYLKLENQSLKSVKFGSIKSDWLGC |
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Drugs and Mode of Action | |||||
Drug(s) | Prinomastat | Drug Info | Approved | Lung cancer; Prostate cancer | [536056], [541642] |
Marimastat | Drug Info | Phase 3 | Pancreatic cancer | [468274], [527314] | |
Metastat | Drug Info | Phase 1 | Acne vulgaris | [521425], [527241] | |
Neovastat | Drug Info | Phase 1 | Non-small-cell lung cancer; Renal cell carcinoma | [537114] | |
ILOMASTAT | Drug Info | Preclinical | Discovery agent | [542432], [544872] | |
RO-26-2853 | Drug Info | Preclinical | Cancer | [536447] | |
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] | |
Tanomastat | Drug Info | Discontinued in Phase 3 | Pancreatic cancer; Lung cancer; Ovarian cancer; Osteoarthritis | [541603], [546781] | |
Galarubicin | Drug Info | Discontinued in Phase 2 | Solid tumours | [545729] | |
RS-130830 | Drug Info | Discontinued in Phase 2 | HCV infection | [546851] | |
BB-1101 | Drug Info | Terminated | Multiple scierosis | [546101] | |
BB-3644 | Drug Info | Terminated | Cancer | [535909] | |
CDP-845 | Drug Info | Terminated | Cancer | [546133] | |
L-696418 | Drug Info | Terminated | Discovery agent | [546087] | |
SC-44463 | Drug Info | Terminated | Discovery agent | [546364] | |
Inhibitor | (+/-)5-(biphenyl-4-yl)-3-hydroxypentanoic acid | Drug Info | [530333] | ||
2-(4'-chloro-biphenyl-4-sulfonyl)-pentanoic acid | Drug Info | [528153] | |||
2-(Biphenyl-4-ylsulfonyl)N-hydroxybenzamide | Drug Info | [530402] | |||
3-(4-(2-phenylethynyl)benzoyl)pentanoic acid | Drug Info | [527972] | |||
3-(4-Phenylethynylbenzoyl)nonanoic acid | Drug Info | [527972] | |||
4-(4-(dec-1-ynyl)phenyl)-4-oxobutanoic acid | Drug Info | [527972] | |||
5-(4-Phenoxy-phenyl)-pyrimidine-2,4,6-trione | Drug Info | [526040] | |||
5-Biphenyl-4-yl-5-ethyl-pyrimidine-2,4,6-trione | Drug Info | [526040] | |||
5-Biphenyl-4-yl-5-hexyl-pyrimidine-2,4,6-trione | Drug Info | [526040] | |||
5-Hexyl-5-phenyl-pyrimidine-2,4,6-trione | Drug Info | [526040] | |||
BB-1101 | Drug Info | [534793] | |||
BB-3644 | Drug Info | [528049], [535909] | |||
BMS 275291 | Drug Info | [528049], [536019], [536073], [536608] | |||
Cis-2-aminocyclohexylcarbamoylphosphonic acid | Drug Info | [529297] | |||
Clinopodic acid C | Drug Info | [530340] | |||
EPIGALOCATECHIN GALLATE | Drug Info | [530210] | |||
Folate gamma-hydroxamic acid | Drug Info | [528548] | |||
Folate gamma-L-proline-hydroxamic acid | Drug Info | [528548] | |||
Galarubicin | Drug Info | [527842] | |||
IK-682 | Drug Info | [526446] | |||
ILOMASTAT | Drug Info | [529683] | |||
L-696418 | Drug Info | [551297] | |||
Lithospermic acid | Drug Info | [530340] | |||
Marimastat | Drug Info | [528049], [536340], [537040], [538064] | |||
Metastat | Drug Info | [535550] | |||
Methotrexate gamma-hydroxamic acid | Drug Info | [528548] | |||
Methotrexate gamma-L-proline-hydroxamic acid | Drug Info | [528548] | |||
MMI270 | Drug Info | [525533] | |||
N-Hydroxy-2-(4-phenoxy-benzenesulfonyl)benzamide | Drug Info | [530402] | |||
N-hydroxy-3-(2-oxo-2H-chromen-3-yl)propanamide | Drug Info | [529102] | |||
N-hydroxy-3-(6-methoxy-2-oxo-2H-chromen-3-yl) | Drug Info | [529102] | |||
Neovastat | Drug Info | [535315], [535341], [536060] | |||
PD-169469 | Drug Info | [527998] | |||
PNU-107859 | Drug Info | [527091] | |||
Prinomastat | Drug Info | [528049], [536127], [536723], [536808], [537136] | |||
RO-26-2853 | Drug Info | [536447] | |||
Ro-37-9790 | Drug Info | [551326] | |||
Roche 28-2653 | Drug Info | [535433] | |||
RS-130830 | Drug Info | [527412] | |||
SC-44463 | Drug Info | [526680] | |||
SC-74020 | Drug Info | [551393] | |||
SR-973 | Drug Info | [528025] | |||
Tanomastat | Drug Info | [528049], [536178], [536238], [536657] | |||
UK-356618 | Drug Info | [526680] | |||
[2-(Biphenyl-4-sulfonyl)phenyl]acetic Acid | Drug Info | [530402] | |||
Modulator | CDP-845 | Drug Info | [525633] | ||
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
TEP | EXP Info | ||||
Pathways | |||||
KEGG Pathway | Leukocyte transendothelial migration | ||||
GnRH signaling pathway | |||||
Estrogen signaling pathway | |||||
Pathways in cancer | |||||
Proteoglycans in cancer | |||||
Bladder cancer | |||||
NetPath Pathway | Leptin Signaling Pathway | ||||
TCR Signaling Pathway | |||||
ID Signaling Pathway | |||||
PANTHER Pathway | Alzheimer disease-presenilin pathway | ||||
Pathway Interaction Database | LPA receptor mediated events | ||||
Plasma membrane estrogen receptor signaling | |||||
Osteopontin-mediated events | |||||
Validated transcriptional targets of AP1 family members Fra1 and Fra2 | |||||
Angiopoietin receptor Tie2-mediated signaling | |||||
Direct p53 effectors | |||||
amb2 Integrin signaling | |||||
ATF-2 transcription factor network | |||||
FOXM1 transcription factor network | |||||
Regulation of nuclear beta catenin signaling and target gene transcription | |||||
Syndecan-2-mediated signaling events | |||||
Reactome | Collagen degradation | ||||
Degradation of the extracellular matrix | |||||
Activation of Matrix Metalloproteinases | |||||
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) | |||||
EPH-ephrin mediated repulsion of cells | |||||
WikiPathways | Activation of Matrix Metalloproteinases | ||||
AGE/RAGE pathway | |||||
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 521425 | ClinicalTrials.gov (NCT00001683) A Phase I Study of Oral COL-3 (NSC-683551), a Matrix Metalloproteinase Inhibitor, in Patients With Refractory Metastatic Cancer. U.S. National Institutes of Health. | ||||
Ref 527241 | A phase I and pharmacokinetic study of Col-3 (Metastat), an oral tetracycline derivative with potent matrix metalloproteinase and antitumor properties. Clin Cancer Res. 2004 Oct 1;10(19):6512-21. | ||||
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 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 536447 | Emerging disease-modifying therapies for the treatment of motor neuron disease/amyotropic lateral sclerosis. Expert Opin Emerg Drugs. 2007 May;12(2):229-52. | ||||
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 541603 | (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: 6468). | ||||
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 545729 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004410) | ||||
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 546133 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006498) | ||||
Ref 546364 | Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007717) | ||||
Ref 525533 | Bioorg Med Chem Lett. 1999 Jun 21;9(12):1691-6.Picking the S1, S1' and S2' pockets of matrix metalloproteinases. A niche for potent acyclic sulfonamide inhibitors. | ||||
Ref 526040 | Bioorg Med Chem Lett. 2001 Apr 23;11(8):969-72.Novel 5,5-disubstitutedpyrimidine-2,4,6-triones as selective MMP inhibitors. | ||||
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 527091 | J Med Chem. 2004 Jun 3;47(12):3065-74.A molecular basis for the selectivity of thiadiazole urea inhibitors with stromelysin-1 and gelatinase-A from generalized born molecular dynamics simulations. | ||||
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 527842 | Inhibitory effect of DA-125, a new anthracyclin analog antitumor agent, on the invasion of human fibrosarcoma cells by down-regulating the matrix metalloproteinases. Biochem Pharmacol. 2005 Dec 19;71(1-2):21-31. Epub 2005 Nov 2. | ||||
Ref 527972 | J Med Chem. 2006 Jan 26;49(2):456-8.Selective inhibition of matrix metalloproteinase isozymes and in vivo protection against emphysema by substituted gamma-keto carboxylic acids. | ||||
Ref 527998 | J Med Chem. 2006 Feb 9;49(3):923-31.Structural insight into the stereoselective inhibition of MMP-8 by enantiomeric sulfonamide phosphonates. | ||||
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 528153 | Bioorg Med Chem Lett. 2006 Jun 15;16(12):3096-100. Epub 2006 May 2.Synthesis and SAR of alpha-sulfonylcarboxylic acids as potent matrix metalloproteinase inhibitors. | ||||
Ref 528548 | Bioorg Med Chem. 2007 Feb 1;15(3):1266-74. Epub 2006 Nov 14.Methotrexate gamma-hydroxamate derivatives as potential dual target antitumor drugs. | ||||
Ref 529102 | Bioorg Med Chem. 2008 Jan 1;16(1):530-5. Epub 2007 Sep 14.Chromen-based TNF-alpha converting enzyme (TACE) inhibitors: design, synthesis, and biological evaluation. | ||||
Ref 529297 | J Med Chem. 2008 Mar 13;51(5):1406-14. Epub 2008 Feb 8.Carbamoylphosphonate matrix metalloproteinase inhibitors 6: cis-2-aminocyclohexylcarbamoylphosphonic acid, a novel orally active antimetastaticmatrix metalloproteinase-2 selective inhibitor--synthesis and pharmacodynamic and pharmacokinetic analysis. | ||||
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 530210 | Bioorg Med Chem Lett. 2009 Aug 1;19(15):4171-4. Epub 2009 Jun 2.Regioselective synthesis of methylated epigallocatechin gallate via nitrobenzenesulfonyl (Ns) protecting group. | ||||
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 530340 | J Nat Prod. 2009 Aug;72(8):1379-84.Matrix metalloproteinase-2 inhibitors from Clinopodium chinense var. parviflorum. | ||||
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 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 535315 | Neovastat, a naturally occurring multifunctional antiangiogenic drug, in phase III clinical trials. Semin Oncol. 2001 Dec;28(6):620-5. | ||||
Ref 535341 | The effect of Neovastat (AE-941) on an experimental metastatic bone tumor model. Int J Oncol. 2002 Feb;20(2):299-303. | ||||
Ref 535433 | The new synthetic matrix metalloproteinase inhibitor (Roche 28-2653) reduces tumor growth and prolongs survival in a prostate cancer standard rat model. Oncogene. 2002 Mar 27;21(13):2089-96. | ||||
Ref 535550 | Strategies for MMP inhibition in cancer: innovations for the post-trial era. Nat Rev Cancer. 2002 Sep;2(9):657-72. | ||||
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 536060 | Neovastat (AE-941) inhibits the airway inflammation and hyperresponsiveness in a murine model of asthma. J Microbiol. 2005 Feb;43(1):11-6. | ||||
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 536178 | A phase III randomized trial of BAY 12-9566 (tanomastat) as maintenance therapy in patients with advanced ovarian cancer responsive to primary surgery and paclitaxel/platinum containing chemotherapy:a National Cancer Institute of Canada Clinical Trials Group Study. Gynecol Oncol. 2006 Aug;102(2):300-8. Epub 2006 Jan 25. | ||||
Ref 536238 | Conflicting results from clinical observations and murine models: what is the role of plasminogen activators in tumor growth? J Natl Cancer Inst. 2006 Jun 7;98(11):726-7. | ||||
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 536447 | Emerging disease-modifying therapies for the treatment of motor neuron disease/amyotropic lateral sclerosis. Expert Opin Emerg Drugs. 2007 May;12(2):229-52. | ||||
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 536657 | Radiation therapy and biological compounds for consolidation therapy in advanced ovarian cancer. Int J Gynecol Cancer. 2008 Mar-Apr;18 Suppl 1:44-6. | ||||
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 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). |
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