Target Information
| Target General Information | Top | |||||
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| Target ID |
T08856
(Former ID: TTDR01266)
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| Target Name |
Matrix metalloproteinase-8 (MMP-8)
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| Synonyms |
PMNL-CL; PMNL collagenase; Neutrophil collagenase; CLG1
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| Gene Name |
MMP8
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Rheumatoid arthritis [ICD-11: FA20] | |||||
| Function |
Can degrade fibrillar type I, II, and III collagens.
Click to Show/Hide
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| BioChemical Class |
Peptidase
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| UniProt ID | ||||||
| EC Number |
EC 3.4.24.34
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| Sequence |
MFSLKTLPFLLLLHVQISKAFPVSSKEKNTKTVQDYLEKFYQLPSNQYQSTRKNGTNVIV
EKLKEMQRFFGLNVTGKPNEETLDMMKKPRCGVPDSGGFMLTPGNPKWERTNLTYRIRNY TPQLSEAEVERAIKDAFELWSVASPLIFTRISQGEADINIAFYQRDHGDNSPFDGPNGIL AHAFQPGQGIGGDAHFDAEETWTNTSANYNLFLVAAHEFGHSLGLAHSSDPGALMYPNYA FRETSNYSLPQDDIDGIQAIYGLSSNPIQPTGPSTPKPCDPSLTFDAITTLRGEILFFKD RYFWRRHPQLQRVEMNFISLFWPSLPTGIQAAYEDFDRDLIFLFKGNQYWALSGYDILQG YPKDISNYGFPSSVQAIDAAVFYRSKTYFFVNDQFWRYDNQRQFMEPGYPKSISGAFPGI ESKVDAVFQQEHFFHVFSGPRYYAFDLIAQRVTRVARGNKWLNCRYG Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | AlphaFold | ||||
| HIT2.0 ID | T69OL5 | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | CIPEMASTAT | Drug Info | Phase 3 | Rheumatoid arthritis | [1], [2] | |
| Discontinued Drug(s) | [+] 2 Discontinued Drugs | + | ||||
| 1 | GM6001 | Drug Info | Discontinued in Phase 2 | Corneal ulcer | [3] | |
| 2 | BB-1101 | Drug Info | Terminated | Multiple sclerosis | [4] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | CIPEMASTAT | Drug Info | [1] | |||
| Inhibitor | [+] 22 Inhibitor drugs | + | ||||
| 1 | GM6001 | Drug Info | [5] | |||
| 2 | BB-1101 | Drug Info | [6] | |||
| 3 | SC-44463 | Drug Info | [7] | |||
| 4 | 1-Hydroxyamine-2-Isobutylmalonic Acid | Drug Info | [8] | |||
| 5 | 2-(biphenyl-4-ylsulfonamido)pentanedioic acid | Drug Info | [9] | |||
| 6 | 2-(Biphenyl-4-ylsulfonyl)N-hydroxybenzamide | Drug Info | [10] | |||
| 7 | 2-HYDROXYCARBAMOYL-4-METHYL-PENTANOIC ACID | Drug Info | [11] | |||
| 8 | 2-Thiomethyl-3-Phenylpropanoic Acid | Drug Info | [8] | |||
| 9 | 3-(4-Methoxy-benzenesulfonyl)-cyclohexanethiol | Drug Info | [12] | |||
| 10 | 3-(4-Methoxy-benzenesulfonyl)-propane-1-thiol | Drug Info | [12] | |||
| 11 | 3-(4-Phenoxy-benzenesulfonyl)-cyclohexanethiol | Drug Info | [12] | |||
| 12 | 3-(4-Phenoxy-benzenesulfonyl)-propane-1-thiol | Drug Info | [12] | |||
| 13 | 3-AMINO-AZACYCLOTRIDECAN-2-ONE | Drug Info | [11] | |||
| 14 | 4-amino-3-(4-(hexyloxy)phenyl)-4-oxobutanoic acid | Drug Info | [9] | |||
| 15 | Glycinamid | Drug Info | [8] | |||
| 16 | IK-862 | Drug Info | [13] | |||
| 17 | METHYLAMINO-PHENYLALANYL-LEUCYL-HYDROXAMIC ACID | Drug Info | [11] | |||
| 18 | MMI270 | Drug Info | [14] | |||
| 19 | N-Hydroxy-2-(4-phenoxy-benzenesulfonyl)benzamide | Drug Info | [10] | |||
| 20 | Ro-37-9790 | Drug Info | [15] | |||
| 21 | SL422 | Drug Info | [16] | |||
| 22 | [2-(Biphenyl-4-sulfonyl)phenyl]acetic Acid | Drug Info | [10] | |||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
|---|---|---|---|---|---|---|
| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Regulators | Top | |||||
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| Target-regulating microRNAs | ||||||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| Panther Pathway | [+] 1 Panther Pathways | + | ||||
| 1 | Alzheimer disease-presenilin pathway | |||||
| Reactome | [+] 3 Reactome Pathways | + | ||||
| 1 | Collagen degradation | |||||
| 2 | Degradation of the extracellular matrix | |||||
| 3 | Activation of Matrix Metalloproteinases | |||||
| WikiPathways | [+] 2 WikiPathways | + | ||||
| 1 | Activation of Matrix Metalloproteinases | |||||
| 2 | Matrix Metalloproteinases | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| Target QSAR Model | ||||||
| References | Top | |||||
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| REF 1 | Matrix metalloproteinase inhibition lowers mortality and brain injury in experimental pneumococcal meningitis. Infect Immun. 2014 Apr;82(4):1710-8. | |||||
| REF 2 | URL: 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: 6466). | |||||
| REF 3 | 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 4 | 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 5 | Hydroxamate inhibitors of human gelatinase B (92 kDa), Bioorg. Med. Chem. Lett. 5(4):349-352 (1995). | |||||
| REF 6 | New alpha-substituted succinate-based hydroxamic acids as TNFalpha convertase inhibitors. J Med Chem. 1999 Nov 18;42(23):4890-908. | |||||
| REF 7 | 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 derivati... J Med Chem. 2001 Oct 11;44(21):3347-50. | |||||
| REF 8 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 9 | Ranking the selectivity of PubChem screening hits by activity-based protein profiling: MMP13 as a case study. Bioorg Med Chem. 2009 Feb 1;17(3):1101-8. | |||||
| REF 10 | Design, synthesis, biological evaluation, and NMR studies of a new series of arylsulfones as selective and potent matrix metalloproteinase-12 inhib... J Med Chem. 2009 Oct 22;52(20):6347-61. | |||||
| REF 11 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
| REF 12 | Synthesis and identification of conformationally constrained selective MMP inhibitors. Bioorg Med Chem Lett. 1999 Jul 5;9(13):1757-60. | |||||
| REF 13 | Discovery of gamma-lactam hydroxamic acids as selective inhibitors of tumor necrosis factor alpha converting enzyme: design, synthesis, and structu... J Med Chem. 2002 Nov 7;45(23):4954-7. | |||||
| REF 14 | Design, synthesis, and biological evaluation of potent thiazine- and thiazepine-based matrix metalloproteinase inhibitors. J Med Chem. 1999 Nov 4;42(22):4547-62. | |||||
| REF 15 | 11,21-Bisphenyl-19-norpregnane derivatives are selective antiglucocorticoids, Bioorg. Med. Chem. Lett. 7(17):2299-2302 (1997). | |||||
| REF 16 | 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. | |||||
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