Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTXOZQ1)

• DTT Name: ApoC-III messenger RNA (APOC3 mRNA)
• Synonyms: Apolipoprotein CIII (mRNA); Apolipoprotein C3 (mRNA); Apolipoprotein C-III (mRNA); ApoC-III (mRNA); Apo-CIII (mRNA)
• Gene Name: APOC3
• DTT Type: Successful target; [1]
• BioChemical Class: mRNA target
• UniProt ID: APOC3_HUMAN
• TTD ID: T86115
• Sequence:
  MQPRVLLVVALLALLASARASEAEDASLLSFMQGYMKHATKTAKDALSSVQESQVAQQAR
  GWVTDGFSSLKDYWSTVKDKFSEFWDLDPEVRPTSAVAA
• Function: Plays a multifaceted role in triglyceride homeostasis. Intracellularly, promotes hepatic very low density lipoprotein 1 (VLDL1) assembly and secretion; extracellularly, attenuates hydrolysis and clearance of triglyceride-rich lipoproteins (TRLs). Impairs the lipolysis of TRLs by inhibiting lipoprotein lipase and the hepatic uptake of TRLs by remnant receptors. Formed of several curved helices connected via semiflexible hinges, so that it can wrap tightly around the curved micelle surface and easily adapt to the different diameters of its natural binding partners. Component of triglyceride-rich very low density lipoproteins (VLDL) and high density lipoproteins (HDL) in plasma.
• KEGG Pathway: PPAR signaling pathway (hsa03320)
• Reactome Pathway:
  HDL-mediated lipid transport (R-HSA-194223)
  Retinoid metabolism and transport (R-HSA-975634)
  Chylomicron-mediated lipid transport (R-HSA-174800)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Volanesorsen	DM1YEPS	Hypertriglyceridemia	5C80.1	Approved	[2]

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ARO-APOC3	DMABKHH	Familial chylomicronemia syndrome	5C80	Phase 3	[3]
Olezarsen	DMNLSFN	Familial chylomicronemia syndrome	5C80	Phase 3	[4]
ISIS-APOCIII	DMX3FN4	Atherosclerosis	BD40	Phase 1	[1]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Coronary artery disease	BA80-BA8Z	Peripheral blood	2.67E-01	0.1	0.59

References

• [1] Clinical pipeline report, company report or official report of ISIS Pharmaceuticals (2011).
• [2] Metabolism and Disposition of Volanesorsen, a 2'- O-(2 methoxyethyl) Antisense Oligonucleotide, Across Species. Drug Metab Dispos. 2019 Oct;47(10):1164-1173.
• [3] ANGPTL3 and Apolipoprotein C-III as Novel Lipid-Lowering Targets. Curr Atheroscler Rep. 2021 Mar 10;23(5):20.
• [4] Apolipoprotein C-III reduction in subjects with moderate hypertriglyceridaemia and at high cardiovascular risk. Eur Heart J. 2022 Apr 6;43(14):1401-1412.