Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTRHEQ4)

• DTT Name: Diacylglycerol O-acyltransferase 2 (DGAT2)
• Synonyms: UNQ738/PRO1433; HMFN1045; Diglyceride acyltransferase 2
• Gene Name: DGAT2
• DTT Type: Successful target; [1]
• BioChemical Class: Acyltransferase
• UniProt ID: DGAT2_HUMAN
• TTD ID: T95558
• EC Number: EC 2.3.1.20
• Sequence:
  MKTLIAAYSGVLRGERQAEADRSQRSHGGPALSREGSGRWGTGSSILSALQDLFSVTWLN
  RSKVEKQLQVISVLQWVLSFLVLGVACSAILMYIFCTDCWLIAVLYFTWLVFDWNTPKKG
  GRRSQWVRNWAVWRYFRDYFPIQLVKTHNLLTTRNYIFGYHPHGIMGLGAFCNFSTEATE
  VSKKFPGIRPYLATLAGNFRMPVLREYLMSGGICPVSRDTIDYLLSKNGSGNAIIIVVGG
  AAESLSSMPGKNAVTLRNRKGFVKLALRHGADLVPIYSFGENEVYKQVIFEEGSWGRWVQ
  KKFQKYIGFAPCIFHGRGLFSSDTWGLVPYSKPITTVVGEPITIPKLEHPTQQDIDLYHT
  MYMEALVKLFDKHKTKFGLPETEVLEVN
• Function: Required for synthesis and storage of intracellular triglycerides. Probably plays a central role in cytosolic lipid accumulation. In liver, is primarily responsible for incorporating endogenously synthesized fatty acids into triglycerides. Functions also as an acyl-CoA retinol acyltransferase (ARAT). Essential acyltransferase that catalyzes the terminal and only committed step in triacylglycerol synthesis by using diacylglycerol and fatty acyl CoA as substrates.
• KEGG Pathway:
  Glycerolipid metabolism (hsa00561)
  Metabolic pathways (hsa01100)
  Fat digestion and absorption (hsa04975)
• Reactome Pathway:
  Triglyceride Biosynthesis (R-HSA-75109)
  Acyl chain remodeling of DAG and TAG (R-HSA-1482883)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Vitamin B3	DMQVRZH	Chronic renal failure	GB61.Z	Approved	[1]

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ARI-3037MO	DM9LNXS	Cardiovascular disease	BA00-BE2Z	Phase 2	[2]
PF-06865571	DMZE3GK	Non-alcoholic steatohepatitis	DB92.1	Phase 2	[3]
PF-06427878	DMGB32Z	Cardiovascular disease	BA00-BE2Z	Phase 1	[4]

2 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID25470667-Compound-Figure4-1A	DMMVQW8	N. A.	N. A.	Patented	[5]
PMID25470667-Compound-roselipins	DMCF2G7	N. A.	N. A.	Patented	[5]

References

• [1] Hakozaki T, Minwalla L, Zhuang J, Chhoa M, Matsubara A, Miyamoto K, Greatens A, Hillebrand GG, Bissett DL, Boissy RE: The effect of niacinamide on reducing cutaneous pigmentation and suppression of melanosome transfer. Br J Dermatol. 2002 Jul;147(1):20-31.
• [2] 2011 Pipeline of Arisaph Pharmaceuticals.
• [3] Discovery of Ervogastat (PF-06865571): A Potent and Selective Inhibitor of Diacylglycerol Acyltransferase 2 for the Treatment of Non-alcoholic Steatohepatitis. J Med Chem. 2022 Nov 24;65(22):15000-15013.
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] Acyltransferase inhibitors: a patent review (2010-present).Expert Opin Ther Pat. 2015 Feb;25(2):145-58.