Target Information
Target General Infomation | |||||
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Target ID |
T54156
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Former ID |
TTDC00076
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Target Name |
MMP-9
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Gene Name |
MMP9
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Synonyms |
92 kDa gelatinase; GELB; Gelatinase B; MMP-9; Matrix metalloproteinase 9; Matrix metalloproteinase-9; MMP9
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Target Type |
Clinical Trial
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Disease | Cancer [ICD9: 140-229; ICD10: C00-C96] | ||||
Colorectal cancer [ICD9: 153, 154; ICD10: C18-C21] | |||||
HCV infection [ICD9: 070.4, 070.5, 070.70; ICD10: B17.1, B18.2] | |||||
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] | |||||
Rheumatoid arthritis [ICD9: 710-719, 714; ICD10: M05-M06] | |||||
Solid tumours; Ulcerative colitis [ICD9:140-199, 210-229, 556; ICD10: C00-D48, K51] | |||||
Stroke [ICD9: 434.91, 437.6, 453, 671.5, 671.9; ICD10: I61-I63, I80-I82] | |||||
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48] | |||||
Function |
May play an essential role in local proteolysis of the extracellular matrix and in leukocyte migration. Could play a role in bone osteoclastic resorption. Cleaves KiSS1 at a Gly-|-Leu bond. Cleaves type IV and type V collagen into largeC-terminal three quarter fragments and shorter N-terminal one quarter fragments. Degrades fibronectin but not laminin or Pz-peptide.
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BioChemical Class |
Peptidase
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Target Validation |
T54156
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UniProt ID | |||||
EC Number |
EC 3.4.24.35
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Sequence |
MSLWQPLVLVLLVLGCCFAAPRQRQSTLVLFPGDLRTNLTDRQLAEEYLYRYGYTRVAEM
RGESKSLGPALLLLQKQLSLPETGELDSATLKAMRTPRCGVPDLGRFQTFEGDLKWHHHN ITYWIQNYSEDLPRAVIDDAFARAFALWSAVTPLTFTRVYSRDADIVIQFGVAEHGDGYP FDGKDGLLAHAFPPGPGIQGDAHFDDDELWSLGKGVVVPTRFGNADGAACHFPFIFEGRS YSACTTDGRSDGLPWCSTTANYDTDDRFGFCPSERLYTQDGNADGKPCQFPFIFQGQSYS ACTTDGRSDGYRWCATTANYDRDKLFGFCPTRADSTVMGGNSAGELCVFPFTFLGKEYST CTSEGRGDGRLWCATTSNFDSDKKWGFCPDQGYSLFLVAAHEFGHALGLDHSSVPEALMY PMYRFTEGPPLHKDDVNGIRHLYGPRPEPEPRPPTTTTPQPTAPPTVCPTGPPTVHPSER PTAGPTGPPSAGPTGPPTAGPSTATTVPLSPVDDACNVNIFDAIAEIGNQLYLFKDGKYW RFSEGRGSRPQGPFLIADKWPALPRKLDSVFEERLSKKLFFFSGRQVWVYTGASVLGPRR LDKLGLGADVAQVTGALRSGRGKMLLFSGRRLWRFDVKAQMVDPRSASEVDRMFPGVPLD THDVFQYREKAYFCQDRFYWRVSSRSELNQVDQVGYVTYDILQCPED |
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Structure |
1CK7; 1CXW; 1EAK; 1GEN; 1GXD; 1HOV; 1J7M; 1KS0; 1QIB; 1RTG; 3AYU; 1GKC; 1GKD; 1ITV; 1L6J; 1LKG; 2OVX; 2OVZ; 2OW0; 2OW1; 2OW2; 4H1Q; 4H2E; 4H3X; 4H82; 4HMA; 4JIJ; 4JQG
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Drugs and Mode of Action | |||||
Drug(s) | Curcumin | Drug Info | Phase 3 | Cancer | [532348], [542031] |
DP-b99 | Drug Info | Phase 3 | Stroke | [522654] | |
GS-5745 | Drug Info | Phase 2 | Solid tumours; Ulcerative colitis | [525136] | |
Neovastat | Drug Info | Phase 1 | Non-small-cell lung cancer; Renal cell carcinoma | [537114] | |
DX-2802 | Drug Info | Preclinical | Cancer | [548299] | |
ILOMASTAT | Drug Info | Preclinical | Discovery agent | [542432], [544872] | |
Galarubicin | Drug Info | Discontinued in Phase 2 | Solid tumours | [545729] | |
RS-130830 | Drug Info | Discontinued in Phase 2 | HCV infection | [546851] | |
CDP-845 | Drug Info | Terminated | Cancer | [546133] | |
CT-1746 | Drug Info | Terminated | Colorectal cancer | [546133] | |
RO-319790 | Drug Info | Terminated | Rheumatoid arthritis | [545173] | |
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-ylsulfonamido)pentanedioic acid | Drug Info | [529392] | |||
2-(Biphenyl-4-ylsulfonyl)N-hydroxybenzamide | Drug Info | [530402] | |||
2-Amino-N,3,3-Trimethylbutanamide | Drug Info | [551393] | |||
3-(4-(2-phenylethynyl)benzoyl)pentanoic acid | Drug Info | [527972] | |||
3-(4-Phenylethynylbenzoyl)nonanoic acid | Drug Info | [527972] | |||
4-amino-3-(4-(hexyloxy)phenyl)-4-oxobutanoic acid | Drug Info | [529392] | |||
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] | |||
5-Methyl-5-phenyl-pyrimidine-2,4,6-trione | Drug Info | [526040] | |||
ARP100 | Drug Info | [528042] | |||
Carboxylated glucosamine | Drug Info | [528137] | |||
compound 1a | Drug Info | [527019] | |||
compound 29e | Drug Info | [532333] | |||
Curcumin | Drug Info | [529906] | |||
DP-b99 | Drug Info | [532838] | |||
Folate gamma-hydroxamic acid | Drug Info | [528548] | |||
Galarubicin | Drug Info | [527842] | |||
IK-682 | Drug Info | [526446] | |||
ILOMASTAT | Drug Info | [529683] | |||
Methotrexate gamma-hydroxamic acid | Drug Info | [528548] | |||
Methotrexate gamma-L-phenylalaninehydroxamic acid | Drug Info | [528548] | |||
Methotrexate gamma-L-proline-hydroxamic acid | Drug Info | [528548] | |||
MMI270 | Drug Info | [525533] | |||
N-hydroxy-2,3-bis(phenylsulfonamido)propanamide | Drug Info | [529443] | |||
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] | |||
Ro 28-2653 | Drug Info | [535433] | |||
RO-319790 | Drug Info | [534791] | |||
Ro-37-9790 | Drug Info | [551326] | |||
Roche 28-2653 | Drug Info | [535433] | |||
RS-130830 | Drug Info | [527412] | |||
SC-44463 | Drug Info | [526154] | |||
SL422 | Drug Info | [526113] | |||
SR-973 | Drug Info | [528025] | |||
UK-356618 | Drug Info | [526680] | |||
[2-(Biphenyl-4-sulfonyl)phenyl]acetic Acid | Drug Info | [530402] | |||
Modulator | CDP-845 | Drug Info | [525633] | ||
CT-1746 | Drug Info | [534338] | |||
GS-5745 | Drug Info | [550496] | |||
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
TEP | EXP Info | ||||
Pathways | |||||
KEGG Pathway | TNF signaling pathway | ||||
Leukocyte transendothelial migration | |||||
Estrogen signaling pathway | |||||
Hepatitis B | |||||
Pathways in cancer | |||||
Transcriptional misregulation in cancer | |||||
Proteoglycans in cancer | |||||
MicroRNAs in cancer | |||||
Bladder cancer | |||||
NetPath Pathway | ID Signaling Pathway | ||||
TWEAK Signaling Pathway | |||||
Leptin Signaling Pathway | |||||
TNFalpha Signaling Pathway | |||||
PANTHER Pathway | Alzheimer disease-presenilin pathway | ||||
Plasminogen activating cascade | |||||
CCKR signaling map ST | |||||
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 | |||||
Validated targets of C-MYC transcriptional activation | |||||
CXCR4-mediated signaling events | |||||
amb2 Integrin signaling | |||||
Syndecan-4-mediated signaling events | |||||
AP-1 transcription factor network | |||||
Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling | |||||
Syndecan-1-mediated signaling events | |||||
Regulation of nuclear beta catenin signaling and target gene transcription | |||||
FGF signaling pathway | |||||
Reactome | Collagen degradation | ||||
Degradation of the extracellular matrix | |||||
Activation of Matrix Metalloproteinases | |||||
Assembly of collagen fibrils and other multimeric structures | |||||
EPH-ephrin mediated repulsion of cells | |||||
WikiPathways | Endochondral Ossification | ||||
IL1 and megakaryotyces in obesity | |||||
Mammary gland development pathway - Involution (Stage 4 of 4) | |||||
Activation of Matrix Metalloproteinases | |||||
Degradation of collagen | |||||
Spinal Cord Injury | |||||
AGE/RAGE pathway | |||||
TWEAK Signaling Pathway | |||||
Angiogenesis | |||||
Osteopontin Signaling | |||||
Matrix Metalloproteinases | |||||
References | |||||
Ref 522654 | ClinicalTrials.gov (NCT00893867) Efficacy and Safety Study of DP-b99 in Treating Acute Ischemic Stroke. U.S. National Institutes of Health. | ||||
Ref 525136 | ClinicalTrials.gov (NCT02405442) Safety and Efficacy of GS-5745 in Participants With Moderately to Severely Active Crohn's Disease. U.S. National Institutes of Health. | ||||
Ref 532348 | Nanocurcumin: a promising therapeutic advancement over native curcumin. Crit Rev Ther Drug Carrier Syst. 2013;30(4):331-68. | ||||
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 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 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 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 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 526154 | J Med Chem. 2001 Oct 11;44(21):3347-50.Design and synthesis of a series of (2R)-N(4)-hydroxy-2-(3-hydroxybenzyl)-N(1)- [(1S,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]butanediamide derivatives as potent, selective, and orally bioavailable aggrecanase 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 527019 | Azasugar-based MMP/ADAM inhibitors as antipsoriatic agents. J Med Chem. 2004 Apr 8;47(8):1930-8. | ||||
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 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 528042 | Amber force field implementation, molecular modelling study, synthesis and MMP-1/MMP-2 inhibition profile of (R)- and (S)-N-hydroxy-2-(N-isopropoxybiphenyl-4-ylsulfonamido)-3-methylbutanamides. Bioorg Med Chem. 2006 Jun 15;14(12):4260-76. Epub 2006 Feb 17. | ||||
Ref 528137 | Bioorg Med Chem Lett. 2006 Jun 15;16(12):3105-10. Epub 2006 Apr 17.Carboxy derivatized glucosamine is a potent inhibitor of matrix metalloproteinase-9 in HT1080 cells. | ||||
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 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 529443 | Bioorg Med Chem Lett. 2008 Jun 1;18(11):3333-7. Epub 2008 Apr 16.Novel bis-(arylsulfonamide) hydroxamate-based selective 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 529906 | Bioorg Med Chem. 2009 Feb 1;17(3):1290-6. Epub 2009 Jan 6.Synthesis and biological evaluation of curcuminoid pyrazoles as new therapeutic agents in inflammatory bowel disease: effect on matrix metalloproteinases. | ||||
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 532333 | Matrix metalloproteinase inhibitors based on the 3-mercaptopyrrolidine core. J Med Chem. 2013 Jun 13;56(11):4357-73. | ||||
Ref 532838 | DP-b99 modulates matrix metalloproteinase activity and neuronal plasticity. PLoS One. 2014 Jun 11;9(6):e99789. | ||||
Ref 534338 | Conversion of highly malignant colon cancer from an aggressive to a controlled disease by oral administration of a metalloproteinase inhibitor. Clin Exp Metastasis. 1997 Mar;15(2):184-95. | ||||
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 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 536060 | Neovastat (AE-941) inhibits the airway inflammation and hyperresponsiveness in a murine model of asthma. J Microbiol. 2005 Feb;43(1):11-6. |
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