Target Information

Target General Infomation
Target ID
T86702
Former ID
TTDC00105
Target Name
Stromelysin-1
Gene Name
MMP3
Synonyms
MMP-3; Matrix metalloproteinase 3; Matrix metalloproteinase-3; SL-1; Transin-1; MMP3
Target Type
Research
Disease Corneal ulcers [ICD9: 370; ICD10: H16.0]
HCV infection [ICD9: 070.4, 070.5, 070.70; ICD10: B17.1, B18.2]
Ischemic stroke [ICD9: 434.91; ICD10: I61-I63]
Multiple scierosis [ICD9: 340; ICD10: G35]
Osteoarthritis; Myocardial infarction [ICD9: 410, 715; ICD10: I21, I22, M15-M19, M47]
Rheumatoid arthritis [ICD9: 710-719, 714; ICD10: M05-M06]
Function
Can degrade fibronectin, laminin, gelatins of type I, III, IV, and V; collagens III, IV, X, and IX, and cartilage proteoglycans. Activates procollagenase.
BioChemical Class
Peptidase
Target Validation
T86702
UniProt ID
P08254
EC Number
EC 3.4.24.17
Sequence
MKSLPILLLLCVAVCSAYPLDGAARGEDTSMNLVQKYLENYYDLKKDVKQFVRRKDSGPV
VKKIREMQKFLGLEVTGKLDSDTLEVMRKPRCGVPDVGHFRTFPGIPKWRKTHLTYRIVN
YTPDLPKDAVDSAVEKALKVWEEVTPLTFSRLYEGEADIMISFAVREHGDFYPFDGPGNV
LAHAYAPGPGINGDAHFDDDEQWTKDTTGTNLFLVAAHEIGHSLGLFHSANTEALMYPLY
HSLTDLTRFRLSQDDINGIQSLYGPPPDSPETPLVPTEPVPPEPGTPANCDPALSFDAVS
TLRGEILIFKDRHFWRKSLRKLEPELHLISSFWPSLPSGVDAAYEVTSKDLVFIFKGNQF
WAIRGNEVRAGYPRGIHTLGFPPTVRKIDAAISDKEKNKTYFFVEDKYWRFDEKRNSMEP
GFPKQIAEDFPGIDSKIDAVFEEFGFFYFFTGSSQLEFDPNAKKVTHTLKSNSWLNC
Drugs and Mode of Action
Drug(s) ILOMASTAT Drug Info Preclinical Discovery agent [542432], [544872]
Batimastat Drug Info Discontinued in Phase 3 Ischemic stroke [468208], [545311]
Galardin Drug Info Discontinued in Phase 2 Corneal ulcers [544872]
PG-530742 Drug Info Discontinued in Phase 2 Osteoarthritis; Myocardial infarction [536172]
RS-130830 Drug Info Discontinued in Phase 2 HCV infection [546851]
BB-1101 Drug Info Terminated Multiple scierosis [546101]
L-696418 Drug Info Terminated Discovery agent [546087]
RO-319790 Drug Info Terminated Rheumatoid arthritis [545173]
SC-44463 Drug Info Terminated Discovery agent [546364]
Inhibitor 1-Methyloxy-4-Sulfone-Benzene Drug Info [551393]
3-Methylpyridine Drug Info [551393]
5-Biphenyl-4-yl-5-ethyl-pyrimidine-2,4,6-trione Drug Info [526040]
8-chloro-quinoline-3-carbonitrile Drug Info [529035]
AM-2S Drug Info [529997]
BB-1101 Drug Info [534793]
CM-352 Drug Info [533140]
FUTOENONE Drug Info [551279]
Galardin Drug Info [528485], [529239]
Hydroxyaminovaline Drug Info [551393]
IK-682 Drug Info [526446]
ILOMASTAT Drug Info [529683]
L-696418 Drug Info [551297]
MMI270 Drug Info [535550]
PD-169469 Drug Info [527998]
PG-530742 Drug Info [528049], [536172]
PKF-242-484 Drug Info [528065]
PNU-107859 Drug Info [527091]
PNU-142372 Drug Info [526419]
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 [551328]
UK-356618 Drug Info [526680]
Modulator Batimastat Drug Info
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
KEGG Pathway TNF signaling pathway
Transcriptional misregulation in cancer
Rheumatoid arthritis
NetPath Pathway IL1 Signaling Pathway
IL4 Signaling Pathway
PANTHER Pathway Plasminogen activating cascade
CCKR signaling map ST
Pathway Interaction Database Posttranslational regulation of adherens junction stability and dissassembly
p75(NTR)-mediated signaling
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
EGFR Transactivation by Gastrin
WikiPathways Activation of Matrix Metalloproteinases
Gastrin-CREB signalling pathway via PKC and MAPK
Oncostatin M Signaling Pathway
Matrix Metalloproteinases
References
Ref 468208(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: 5145).
Ref 536172Selective 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 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 545311Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002787)
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 526040Bioorg Med Chem Lett. 2001 Apr 23;11(8):969-72.Novel 5,5-disubstitutedpyrimidine-2,4,6-triones as selective MMP inhibitors.
Ref 526419Bioorg Med Chem Lett. 2002 Oct 7;12(19):2667-72.Protease inhibitors: synthesis of matrix metalloproteinase and bacterial collagenase inhibitors incorporating 5-amino-2-mercapto-1,3,4-thiadiazole zincbinding functions.
Ref 526446J 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 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 527091J 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 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 527998J Med Chem. 2006 Feb 9;49(3):923-31.Structural insight into the stereoselective inhibition of MMP-8 by enantiomeric sulfonamide phosphonates.
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 528485Blockade of tumor necrosis factor-alpha-converting enzyme improves experimental small intestinal damage by decreasing matrix metalloproteinase-3 production in rats. Scand J Gastroenterol. 2006 Nov;41(11):1320-9.
Ref 529035J Biol Chem. 2007 Nov 16;282(46):33295-304. Epub 2007 Sep 11.Pharmacologic inhibition of tpl2 blocks inflammatory responses in primary human monocytes, synoviocytes, and blood.
Ref 529239Novel transcription-factor-like function of human matrix metalloproteinase 3 regulating the CTGF/CCN2 gene. Mol Cell Biol. 2008 Apr;28(7):2391-413.
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 529997Bioorg Med Chem Lett. 2009 Apr 1;19(7):1970-6. Epub 2009 Feb 14.Synthesis of hydroxypyrone- and hydroxythiopyrone-based matrix metalloproteinase inhibitors: developing a structure-activity relationship.
Ref 533140Discovery and safety profiling of a potent preclinical candidate, (4-[4-[[(3R)-3-(hydroxycarbamoyl)-8-azaspiro[4.5]decan-3-yl]sulfonyl]phenoxy]-N-methylbenzamide) (CM-352), for the prevention and treatment of hemorrhage. J Med Chem. 2015 Apr 9;58(7):2941-57.
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 535550Strategies for MMP inhibition in cancer: innovations for the post-trial era. Nat Rev Cancer. 2002 Sep;2(9):657-72.
Ref 536172Selective 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 551279Inhibition of metalloproteinase by futoenone derivatives, Bioorg. Med. Chem. Lett. 5(15):1637-1642 (1995).
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 551328Amide surrogates of matrix metalloproteinase inhibitors: Urea and sulfonamide mimics, Bioorg. Med. Chem. Lett. 7(18):2331-2336 (1997).
Ref 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
Ref 1587926URL: https://www.ebi.ac.uk/chembl/ The ChEMBL database in 2017

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