General Information of Drug Therapeutic Target (DTT) (ID: TT59GO7)

DTT Name ANGPTL3 messenger RNA (ANGPTL3 mRNA)
Synonyms UNQ153/PRO179 (mRNA); Angiopoietin-related protein 3 (mRNA); Angiopoietin-like protein 3 (mRNA); Angiopoietin-5 (mRNA); ANGPT5 (mRNA); ANG-5 (mRNA)
Gene Name ANGPTL3
DTT Type
Clinical trial target
[1]
BioChemical Class
mRNA target
UniProt ID
ANGL3_HUMAN
TTD ID
T88697
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MFTIKLLLFIVPLVISSRIDQDNSSFDSLSPEPKSRFAMLDDVKILANGLLQLGHGLKDF
VHKTKGQINDIFQKLNIFDQSFYDLSLQTSEIKEEEKELRRTTYKLQVKNEEVKNMSLEL
NSKLESLLEEKILLQQKVKYLEEQLTNLIQNQPETPEHPEVTSLKTFVEKQDNSIKDLLQ
TVEDQYKQLNQQHSQIKEIENQLRRTSIQEPTEISLSSKPRAPRTTPFLQLNEIRNVKHD
GIPAECTTIYNRGEHTSGMYAIRPSNSQVFHVYCDVISGSPWTLIQHRIDGSQNFNETWE
NYKYGFGRLDGEFWLGLEKIYSIVKQSNYVLRIELEDWKDNKHYIEYSFYLGNHETNYTL
HLVAITGNVPNAIPENKDLVFSTWDHKAKGHFNCPEGYSGGWWWHDECGENNLNGKYNKP
RAKSKPERRRGLSWKSQNGRLYSIKSTKMLIHPTDSESFE
Function
Proposed to play a role in the trafficking of energy substrates to either storage or oxidative tissues in response to food intake. Has a stimulatory effect on plasma triglycerides (TG), which is achieved by suppressing plasma TG clearance via inhibition of LPL activity. The inhibition of LPL activity appears to be an indirect mechanism involving recruitment of proprotein convertases PCSK6 and FURIN to LPL leading to cleavage and dissociation of LPL from the cell surface; the function does not require ANGPTL3 proteolytic cleavage but seems to be mediated by the N-terminal domain, and is not inhibited by GPIHBP1. Can inhibit endothelial lipase, causing increased plasma levels of high density lipoprotein (HDL) cholesterol and phospholipids. Can bind to adipocytes to activate lipolysis, releasing free fatty acids and glycerol. Suppresses LPL specifically in oxidative tissues which is required to route very low density lipoprotein (VLDL)-TG to white adipose tissue (WAT) for storage in response to food; the function may involve cooperation with circulating, liver-derived ANGPTL8 and ANGPTL4 expression in WAT. Contributes to lower plasma levels of low density lipoprotein (LDL)-cholesterol by a mechanism that is independent of the canonical pathway implicating APOE and LDLR. May stimulate hypothalamic LPL activity. Acts in part as a hepatokine that is involved in regulation of lipid and glucose metabolism.
KEGG Pathway
Cholesterol metabolism (hsa04979 )
Reactome Pathway
NR1H2 & NR1H3 regulate gene expression linked to lipogenesis (R-HSA-9029558 )
Assembly of active LPL and LIPC lipase complexes (R-HSA-8963889 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
3 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
ARO-ANG3 DM3PDL8 Dyslipidemia 5C80-5C81 Phase 2 [2]
Vupanorsen DMN6J18 Hypertriglyceridemia 5C80.1 Phase 2 [3]
ISIS-ANGPTL3 DM9Y51T Hyperlipidaemia 5C80 Phase 1 [1]
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References

1 Clinical pipeline report, company report or official report of ISIS Pharmaceuticals.
2 ANGPTL3 and Apolipoprotein C-III as Novel Lipid-Lowering Targets. Curr Atheroscler Rep. 2021 Mar 10;23(5):20.
3 Clinical pipeline report, company report or official report of Ionis Pharmaceuticals.