Target Information

Target General Infomation
Target ID
T54156
Former ID
TTDC00076
Target Name
MMP-9
Gene Name
MMP9
Synonyms
92 kDa gelatinase; GELB; Gelatinase B; MMP-9; Matrix metalloproteinase 9; Matrix metalloproteinase-9; MMP9
Target Type
Clinical Trial
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.
BioChemical Class
Peptidase
Target Validation
T54156
UniProt ID
P14780
EC Number
EC 3.4.24.35
Sequence
MSLWQPLVLVLLVLGCCFAAPRQRQSTLVLFPGDLRTNLTDRQLAEEYLYRYGYTRVAEM
RGESKSLGPALLLLQKQLSLPETGELDSATLKAMRTPRCGVPDLGRFQTFEGDLKWHHHN
ITYWIQNYSEDLPRAVIDDAFARAFALWSAVTPLTFTRVYSRDADIVIQFGVAEHGDGYP
FDGKDGLLAHAFPPGPGIQGDAHFDDDELWSLGKGVVVPTRFGNADGAACHFPFIFEGRS
YSACTTDGRSDGLPWCSTTANYDTDDRFGFCPSERLYTQDGNADGKPCQFPFIFQGQSYS
ACTTDGRSDGYRWCATTANYDRDKLFGFCPTRADSTVMGGNSAGELCVFPFTFLGKEYST
CTSEGRGDGRLWCATTSNFDSDKKWGFCPDQGYSLFLVAAHEFGHALGLDHSSVPEALMY
PMYRFTEGPPLHKDDVNGIRHLYGPRPEPEPRPPTTTTPQPTAPPTVCPTGPPTVHPSER
PTAGPTGPPSAGPTGPPTAGPSTATTVPLSPVDDACNVNIFDAIAEIGNQLYLFKDGKYW
RFSEGRGSRPQGPFLIADKWPALPRKLDSVFEERLSKKLFFFSGRQVWVYTGASVLGPRR
LDKLGLGADVAQVTGALRSGRGKMLLFSGRRLWRFDVKAQMVDPRSASEVDRMFPGVPLD
THDVFQYREKAYFCQDRFYWRVSSRSELNQVDQVGYVTYDILQCPED
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
Drugs and Mode of Action
Drug(s) Curcumin Drug Info Phase 3 Cancer [1], [2]
DP-b99 Drug Info Phase 3 Stroke [3]
GS-5745 Drug Info Phase 2 Solid tumours; Ulcerative colitis [4]
Neovastat Drug Info Phase 1 Non-small-cell lung cancer; Renal cell carcinoma [5]
DX-2802 Drug Info Preclinical Cancer [6]
ILOMASTAT Drug Info Preclinical Discovery agent [7], [8]
Galarubicin Drug Info Discontinued in Phase 2 Solid tumours [9]
RS-130830 Drug Info Discontinued in Phase 2 HCV infection [10]
CDP-845 Drug Info Terminated Cancer [11]
CT-1746 Drug Info Terminated Colorectal cancer [11]
RO-319790 Drug Info Terminated Rheumatoid arthritis [12]
SC-44463 Drug Info Terminated Discovery agent [13]
Inhibitor (+/-)5-(biphenyl-4-yl)-3-hydroxypentanoic acid Drug Info [14]
2-(4'-chloro-biphenyl-4-sulfonyl)-pentanoic acid Drug Info [15]
2-(biphenyl-4-ylsulfonamido)pentanedioic acid Drug Info [16]
2-(Biphenyl-4-ylsulfonyl)N-hydroxybenzamide Drug Info [17]
2-Amino-N,3,3-Trimethylbutanamide Drug Info [18]
3-(4-(2-phenylethynyl)benzoyl)pentanoic acid Drug Info [19]
3-(4-Phenylethynylbenzoyl)nonanoic acid Drug Info [19]
4-amino-3-(4-(hexyloxy)phenyl)-4-oxobutanoic acid Drug Info [16]
5-(4-Phenoxy-phenyl)-pyrimidine-2,4,6-trione Drug Info [20]
5-Biphenyl-4-yl-5-ethyl-pyrimidine-2,4,6-trione Drug Info [20]
5-Biphenyl-4-yl-5-hexyl-pyrimidine-2,4,6-trione Drug Info [20]
5-Hexyl-5-phenyl-pyrimidine-2,4,6-trione Drug Info [20]
5-Methyl-5-phenyl-pyrimidine-2,4,6-trione Drug Info [20]
ARP100 Drug Info [21]
Carboxylated glucosamine Drug Info [22]
compound 1a Drug Info [23]
compound 29e Drug Info [24]
Curcumin Drug Info [25]
DP-b99 Drug Info [26]
Folate gamma-hydroxamic acid Drug Info [27]
Galarubicin Drug Info [28]
IK-682 Drug Info [29]
ILOMASTAT Drug Info [30]
Methotrexate gamma-hydroxamic acid Drug Info [27]
Methotrexate gamma-L-phenylalaninehydroxamic acid Drug Info [27]
Methotrexate gamma-L-proline-hydroxamic acid Drug Info [27]
MMI270 Drug Info [31]
N-hydroxy-2,3-bis(phenylsulfonamido)propanamide Drug Info [32]
N-Hydroxy-2-(4-phenoxy-benzenesulfonyl)benzamide Drug Info [17]
N-hydroxy-3-(2-oxo-2H-chromen-3-yl)propanamide Drug Info [33]
N-hydroxy-3-(6-methoxy-2-oxo-2H-chromen-3-yl) Drug Info [33]
Neovastat Drug Info [34], [35], [36]
Ro 28-2653 Drug Info [37]
RO-319790 Drug Info [38]
Ro-37-9790 Drug Info [39]
Roche 28-2653 Drug Info [37]
RS-130830 Drug Info [40]
SC-44463 Drug Info [41]
SL422 Drug Info [42]
SR-973 Drug Info [43]
UK-356618 Drug Info [44]
[2-(Biphenyl-4-sulfonyl)phenyl]acetic Acid Drug Info [17]
Modulator CDP-845 Drug Info [45]
CT-1746 Drug Info [46]
GS-5745 Drug Info [47]
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 1Nanocurcumin: a promising therapeutic advancement over native curcumin. Crit Rev Ther Drug Carrier Syst. 2013;30(4):331-68.
REF 2(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 3ClinicalTrials.gov (NCT00893867) Efficacy and Safety Study of DP-b99 in Treating Acute Ischemic Stroke. U.S. National Institutes of Health.
REF 4ClinicalTrials.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 5Emerging therapies for multiple myeloma. Expert Opin Emerg Drugs. 2009 Mar;14(1):99-127.
REF 6Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800024278)
REF 7(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 8Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001387)
REF 9Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004410)
REF 10Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800010620)
REF 11Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800006498)
REF 12Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002350)
REF 13Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800007717)
REF 14Bioorg 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 15Bioorg 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 16Bioorg 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 17J 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 18How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
REF 19J 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 20Bioorg Med Chem Lett. 2001 Apr 23;11(8):969-72.Novel 5,5-disubstitutedpyrimidine-2,4,6-triones as selective MMP inhibitors.
REF 21Amber 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 22Bioorg 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 23Azasugar-based MMP/ADAM inhibitors as antipsoriatic agents. J Med Chem. 2004 Apr 8;47(8):1930-8.
REF 24Matrix metalloproteinase inhibitors based on the 3-mercaptopyrrolidine core. J Med Chem. 2013 Jun 13;56(11):4357-73.
REF 25Bioorg 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 26DP-b99 modulates matrix metalloproteinase activity and neuronal plasticity. PLoS One. 2014 Jun 11;9(6):e99789.
REF 27Bioorg Med Chem. 2007 Feb 1;15(3):1266-74. Epub 2006 Nov 14.Methotrexate gamma-hydroxamate derivatives as potential dual target antitumor drugs.
REF 28Inhibitory 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 29J 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 30Bioorg 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 31Bioorg 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 32Bioorg Med Chem Lett. 2008 Jun 1;18(11):3333-7. Epub 2008 Apr 16.Novel bis-(arylsulfonamide) hydroxamate-based selective MMP inhibitors.
REF 33Bioorg 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 34Neovastat, a naturally occurring multifunctional antiangiogenic drug, in phase III clinical trials. Semin Oncol. 2001 Dec;28(6):620-5.
REF 35The effect of Neovastat (AE-941) on an experimental metastatic bone tumor model. Int J Oncol. 2002 Feb;20(2):299-303.
REF 36Neovastat (AE-941) inhibits the airway inflammation and hyperresponsiveness in a murine model of asthma. J Microbiol. 2005 Feb;43(1):11-6.
REF 37The 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 38Bioorg 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 3911,21-Bisphenyl-19-norpregnane derivatives are selective antiglucocorticoids, Bioorg. Med. Chem. Lett. 7(17):2299-2302 (1997).
REF 40Bioorg Med Chem Lett. 2005 Feb 15;15(4):1101-6.Structure-based design of potent and selective inhibitors of collagenase-3 (MMP-13).
REF 41J 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 42Design, 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 43Bioorg Med Chem Lett. 2006 May 1;16(9):2357-63. Epub 2006 Feb 10.Synthesis and evaluation of succinoyl-caprolactam gamma-secretase inhibitors.
REF 44J 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 45Clinical potential of matrix metalloprotease inhibitors. Drugs R D. 1999 Feb;1(2):117-29.
REF 46Conversion 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 47National Cancer Institute Drug Dictionary (drug id 747683).

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