Target Information
Target General Information | Top | |||||
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Target ID |
T86652
(Former ID: TTDR01439)
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Target Name |
PCSK9 messenger RNA (PCSK9 mRNA)
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Synonyms |
Subtilisin/kexin-like protease PC9 (mRNA); Proprotein convertase subtilisin/kexin type 9 (mRNA); Proprotein convertase 9 (mRNA); PSEC0052 (mRNA); PC9 (mRNA); Neural apoptosis-regulated convertase 1 (mRNA); NARC1 (mRNA); NARC-1 (mRNA)
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Gene Name |
PCSK9
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Target Type |
Successful target
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[1] | ||||
Disease | [+] 1 Target-related Diseases | + | ||||
1 | Hyper-lipoproteinaemia [ICD-11: 5C80] | |||||
Function |
Binds to low-density lipid receptor family members: low density lipoprotein receptor (LDLR), very low density lipoprotein receptor (VLDLR), apolipoprotein E receptor (LRP1/APOER) and apolipoprotein receptor 2 (LRP8/APOER2), and promotes their degradation in intracellular acidic compartments. Acts via a non-proteolytic mechanism to enhance the degradation of the hepatic LDLR through a clathrin LDLRAP1/ARH-mediated pathway. May prevent the recycling of LDLR from endosomes to the cell surface or direct it to lysosomes for degradation. Can induce ubiquitination of LDLR leading to its subsequent degradation. Inhibits intracellular degradation of APOB via the autophagosome/lysosome pathway in a LDLR-independent manner. Involved in the disposal of non-acetylated intermediates of BACE1 in the early secretory pathway. Inhibits epithelial Na(+) channel (ENaC)-mediated Na(+) absorption by reducing ENaC surface expression primarily by increasing its proteasomal degradation. Regulates neuronal apoptosis via modulation of LRP8/APOER2 levels and related anti-apoptotic signaling pathways. Crucial player in the regulation of plasma cholesterol homeostasis.
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BioChemical Class |
mRNA target
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UniProt ID | ||||||
EC Number |
EC 3.4.21.-
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Sequence |
MGTVSSRRSWWPLPLLLLLLLLLGPAGARAQEDEDGDYEELVLALRSEEDGLAEAPEHGT
TATFHRCAKDPWRLPGTYVVVLKEETHLSQSERTARRLQAQAARRGYLTKILHVFHGLLP GFLVKMSGDLLELALKLPHVDYIEEDSSVFAQSIPWNLERITPPRYRADEYQPPDGGSLV EVYLLDTSIQSDHREIEGRVMVTDFENVPEEDGTRFHRQASKCDSHGTHLAGVVSGRDAG VAKGASMRSLRVLNCQGKGTVSGTLIGLEFIRKSQLVQPVGPLVVLLPLAGGYSRVLNAA CQRLARAGVVLVTAAGNFRDDACLYSPASAPEVITVGATNAQDQPVTLGTLGTNFGRCVD LFAPGEDIIGASSDCSTCFVSQSGTSQAAAHVAGIAAMMLSAEPELTLAELRQRLIHFSA KDVINEAWFPEDQRVLTPNLVAALPPSTHGAGWQLFCRTVWSAHSGPTRMATAVARCAPD EELLSCSSFSRSGKRRGERMEAQGGKLVCRAHNAFGGEGVYAIARCCLLPQANCSVHTAP PAEASMGTRVHCHQQGHVLTGCSSHWEVEDLGTHKPPVLRPRGQPNQCVGHREASIHASC CHAPGLECKVKEHGIPAPQEQVTVACEEGWTLTGCSALPGTSHVLGAYAVDNTCVVRSRD VSTTGSTSEGAVTAVAICCRSRHLAQASQELQ Click to Show/Hide
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Drugs and Modes of Action | Top | |||||
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Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
1 | Inclisiran | Drug Info | Approved | Familial hypercholesterolemia | [2] | |
Clinical Trial Drug(s) | [+] 2 Clinical Trial Drugs | + | ||||
1 | AZD8233 | Drug Info | Phase 2 | Cardiovascular disease | [3] | |
2 | MPSK3169A | Drug Info | Phase 2 | Cardiovascular disease | [4] | |
Preclinical Drug(s) | [+] 2 Preclinical Drugs | + | ||||
1 | ALN-PCS | Drug Info | Preclinical | Hypercholesterolaemia | [5] | |
2 | BMS-PCSK9 | Drug Info | Preclinical | Coronary artery disease | [6] | |
Mode of Action | [+] 2 Modes of Action | + | ||||
Inhibitor | [+] 1 Inhibitor drugs | + | ||||
1 | AZD8233 | Drug Info | [7] | |||
Modulator | [+] 1 Modulator drugs | + | ||||
1 | MPSK3169A | Drug Info | [1] |
Cell-based Target Expression Variations | Top | |||||
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Cell-based Target Expression Variations |
Target Profiles in Patients | Top | |||||
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Target Expression Profile (TEP) |
Target Affiliated Biological Pathways | Top | |||||
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WikiPathways | [+] 1 WikiPathways | + | ||||
1 | PCSK9-mediated LDLR degradation |
References | Top | |||||
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REF 1 | 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. (Target id: 2388). | |||||
REF 2 | FDA Approved Drug Products from FDA Official Website. 2021. Application Number: 214012. | |||||
REF 3 | ClinicalTrials.gov (NCT04964557) A Randomised, Parallel, Double-Blind, Placebo-Controlled Phase 2b Study to Assess the Safety, Tolerability and Efficacy of AZD8233 Treatment in Participants With Hyperlipidaemia. U.S.National Institutes of Health. | |||||
REF 4 | ClinicalTrials.gov (NCT01609140) A Phase II Study of the Safety and Efficacy of MPSK3169A in Patients With Coronary Heart Disease or High Risk of Coronary Heart Disease. U.S. National Institutes of Health. | |||||
REF 5 | Clinical pipeline report, company report or official report of Alnylam Pharmaceuticals, Inc (2011). | |||||
REF 6 | Clinical pipeline report, company report or official report of ISIS Pharmaceuticals (2011). | |||||
REF 7 | AZD8233 antisense oligonucleotide targeting PCSK9 does not prolong QT interval. Br J Clin Pharmacol. 2022 Nov;88(11):4839-4844. |
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