Target Information
Target General Infomation | |||||
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Target ID |
T98896
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Former ID |
TTDR00697
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Target Name |
Aggrecanase
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Gene Name |
ADAMTS5
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Synonyms |
ADAMTS-5; A disintegrin and metalloproteinase with thrombospondinmotifs 5; ADAM-TS 11; ADAM-TS 5; ADAM-TS5; ADMP-2; Aggrecanase-2; ADAMTS5
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Target Type |
Clinical Trial
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Disease | Osteoarthritis [ICD9: 715; ICD10: M15-M19, M47] | ||||
Function |
Cleaves aggrecan, a cartilage proteoglycan, and may be involved in its turnover. May play an important role in the destruction of aggrecan in arthritic diseases. May play a role in proteolytic processing mostly during the peri-implantation period.
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BioChemical Class |
Peptidase
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Target Validation |
T98896
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UniProt ID | |||||
EC Number |
EC 3.4.24.82
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Sequence |
MLLGWASLLLCAFRLPLAAVGPAATPAQDKAGQPPTAAAAAQPRRRQGEEVQERAEPPGH
PHPLAQRRRSKGLVQNIDQLYSGGGKVGYLVYAGGRRFLLDLERDGSVGIAGFVPAGGGT SAPWRHRSHCFYRGTVDGSPRSLAVFDLCGGLDGFFAVKHARYTLKPLLRGPWAEEEKGR VYGDGSARILHVYTREGFSFEALPPRASCETPASTPEAHEHAPAHSNPSGRAALASQLLD QSALSPAGGSGPQTWWRRRRRSISRARQVELLLVADASMARLYGRGLQHYLLTLASIANR LYSHASIENHIRLAVVKVVVLGDKDKSLEVSKNAATTLKNFCKWQHQHNQLGDDHEEHYD AAILFTREDLCGHHSCDTLGMADVGTICSPERSCAVIEDDGLHAAFTVAHEIGHLLGLSH DDSKFCEETFGSTEDKRLMSSILTSIDASKPWSKCTSATITEFLDDGHGNCLLDLPRKQI LGPEELPGQTYDATQQCNLTFGPEYSVCPGMDVCARLWCAVVRQGQMVCLTKKLPAVEGT PCGKGRICLQGKCVDKTKKKYYSTSSHGNWGSWGSWGQCSRSCGGGVQFAYRHCNNPAPR NNGRYCTGKRAIYRSCSLMPCPPNGKSFRHEQCEAKNGYQSDAKGVKTFVEWVPKYAGVL PADVCKLTCRAKGTGYYVVFSPKVTDGTECRLYSNSVCVRGKCVRTGCDGIIGSKLQYDK CGVCGGDNSSCTKIVGTFNKKSKGYTDVVRIPEGATHIKVRQFKAKDQTRFTAYLALKKK NGEYLINGKYMISTSETIIDINGTVMNYSGWSHRDDFLHGMGYSATKEILIVQILATDPT KPLDVRYSFFVPKKSTPKVNSVTSHGSNKVGSHTSQPQWVTGPWLACSRTCDTGWHTRTV QCQDGNRKLAKGCPLSQRPSAFKQCLLKKC |
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Structure |
2RJP; 3B2Z; 4WK7; 4WKE; 4WKI; 2RJQ; 3B8Z; 3HY7; 3HY9; 3HYG; 3LJT
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Drugs and Mode of Action | |||||
Drug(s) | AGG-523 | Drug Info | Phase 1 | Osteoarthritis | [1] |
SC-44463 | Drug Info | Terminated | Discovery agent | [2] | |
Inhibitor | AGG-523 | Drug Info | [3] | ||
Aggrecanase-2 inhibitors | Drug Info | [4] | |||
compound 15c | Drug Info | [5] | |||
CR-5259 | Drug Info | [6] | |||
SC-44463 | Drug Info | [7] | |||
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM) | |||||
TEP | EXP Info | ||||
Pathways | |||||
Reactome | Degradation of the extracellular matrix | ||||
O-glycosylation of TSR domain-containing proteins | |||||
WikiPathways | Endochondral Ossification | ||||
Vitamin D Receptor Pathway | |||||
References | |||||
REF 1 | ClinicalTrials.gov (NCT00454298) Study Evaluating AGG-523 in Subjects With Severe Osteoarthritis Requiring Total Knee Replacement. U.S. National Institutes of Health. | ||||
REF 2 | 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 3 | Elevated aggrecanase activity in a rat model of joint injury is attenuated by an aggrecanase specific inhibitor. Osteoarthritis Cartilage. 2011 Mar;19(3):315-23. | ||||
REF 4 | (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. (Target id: 1678). | ||||
REF 5 | Orally active achiral N-hydroxyformamide inhibitors of ADAM-TS4 (aggrecanase-1) and ADAM-TS5 (aggrecanase-2) for the treatment of osteoarthritis. Bioorg Med Chem Lett. 2011 Jun 1;21(11):3301-6. | ||||
REF 6 | (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. (Target id: 1677). | ||||
REF 7 | 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. |
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