Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTF8P9I)

• DTT Name: Diacylglycerol acyltransferase 1 (DGAT1)
• Synonyms: Retinol O-fatty-acyltransferase; Diglyceride acyltransferase; Diacylglycerol O-acyltransferase 1; DGAT; Acyl-CoA retinol O-fatty-acyltransferase; ARAT; AGRP1; ACAT-related gene product 1
• Gene Name: DGAT1
• DTT Type: Successful target; [1]
• BioChemical Class: Acyltransferase
• UniProt ID: DGAT1_HUMAN
• TTD ID: T16688
• EC Number: EC 2.3.1.20
• Sequence:
  MGDRGSSRRRRTGSRPSSHGGGGPAAAEEEVRDAAAGPDVGAAGDAPAPAPNKDGDAGVG
  SGHWELRCHRLQDSLFSSDSGFSNYRGILNWCVVMLILSNARLFLENLIKYGILVDPIQV
  VSLFLKDPYSWPAPCLVIAANVFAVAAFQVEKRLAVGALTEQAGLLLHVANLATILCFPA
  AVVLLVESITPVGSLLALMAHTILFLKLFSYRDVNSWCRRARAKAASAGKKASSAAAPHT
  VSYPDNLTYRDLYYFLFAPTLCYELNFPRSPRIRKRFLLRRILEMLFFTQLQVGLIQQWM
  VPTIQNSMKPFKDMDYSRIIERLLKLAVPNHLIWLIFFYWLFHSCLNAVAELMQFGDREF
  YRDWWNSESVTYFWQNWNIPVHKWCIRHFYKPMLRRGSSKWMARTGVFLASAFFHEYLVS
  VPLRMFRLWAFTGMMAQIPLAWFVGRFFQGNYGNAAVWLSLIIGQPIAVLMYVHDYYVLN
  YEAPAAEA
• Function: Catalyzes the terminal and only committed step in triacylglycerol synthesis by using diacylglycerol and fatty acyl CoA as substrates. In contrast to DGAT2 it is not essential for survival. May be involved in VLDL (very low density lipoprotein) assembly. In liver, plays a role in esterifying exogenous fatty acids to glycerol. Functions as the major acyl-CoA retinol acyltransferase (ARAT) in the skin, where it acts to maintain retinoid homeostasis and prevent retinoid toxicity leading to skin and hair disorders.
• KEGG Pathway:
  Glycerolipid metabolism (hsa00561)
  Retinol metabolism (hsa00830)
  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
Hesperetin	DMKER83	High blood cholesterol level	5C80.00	Approved	[1]

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LCQ908	DMFLJHQ	Familial chylomicronemia syndrome	5C80	Phase 3	[2]
AZD7687	DMS9I6A	Diabetic complication	5A2Y	Phase 1	[3]
P-7435	DMNZQU5	Diabetic complication	5A2Y	Phase 1	[4]

21 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
amidepsines	DM1FUOY	N. A.	N. A.	Patented	[5]
Azole derivative 6	DMTMJ7S	N. A.	N. A.	Patented	[5]
Azole derivative 7	DMVUJGI	N. A.	N. A.	Patented	[5]
Benzamide derivative 19	DM5YNTM	N. A.	N. A.	Patented	[5]
Carbamide derivative 3	DM4ISCQ	N. A.	N. A.	Patented	[5]
Lactam derivative 1	DMDYKPC	N. A.	N. A.	Patented	[5]
Lactam derivative 2	DMT58QE	N. A.	N. A.	Patented	[5]
Lactam derivative 3	DMD0XIL	N. A.	N. A.	Patented	[5]
Lactam derivative 4	DMJ3ZAI	N. A.	N. A.	Patented	[5]
Lactam derivative 5	DMX5FYZ	N. A.	N. A.	Patented	[5]
PMID25470667-Compound-AZD3988	DM6EN54	N. A.	N. A.	Patented	[5]
PMID25470667-Compound-BAY744113	DMY3140	N. A.	N. A.	Patented	[5]
PMID25470667-Compound-Figure4-1A	DMMVQW8	N. A.	N. A.	Patented	[5]
PMID25470667-Compound-PF-04620110	DM0OBAW	N. A.	N. A.	Patented	[5]
Pyrazine carboxamide derivative 1	DM3RAU4	N. A.	N. A.	Patented	[5]
Pyrazolo[1,5-a]pyrimidine derivative 28	DMG1RNL	N. A.	N. A.	Patented	[5]
Pyrazolo[1,5-a]pyrimidine derivative 29	DMCT6QW	N. A.	N. A.	Patented	[5]
Pyridine-amide derivative 1	DM9KOYX	N. A.	N. A.	Patented	[5]
Pyridine-carboximide derivative 1	DM25M8D	N. A.	N. A.	Patented	[5]
Pyridine-carboximide derivative 2	DMHXWZB	N. A.	N. A.	Patented	[5]
T863	DMX41ZF	Discovery agent	N.A.	Patented	[5]

3 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
DS-7250	DMQK53O	Diabetic complication	5A2Y	Discontinued in Phase 1	[6]
JTT-553	DMI7Z1Y	Obesity	5B81	Discontinued in Phase 1	[7]
PF-04620110	DMSNOH3	Type-2 diabetes	5A11	Terminated	[8]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Type 2 diabetes	5A11	Liver tissue	3.51E-01	-0.41	-0.62

References

• [1] In vitro inhibition of diacylglycerol acyltransferase by prenylflavonoids from Sophora flavescens. Planta Med. 2004 Mar;70(3):258-60.
• [2] DGAT1 inhibitors as anti-obesity and anti-diabetic agents. Curr Opin Drug Discov Devel. 2010 Jul;13(4):489-96.
• [3] Clinical pipeline report, company report or official report of AstraZeneca (2011).
• [4] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800033014)
• [5] Acyltransferase inhibitors: a patent review (2010-present).Expert Opin Ther Pat. 2015 Feb;25(2):145-58.
• [6] Clinical pipeline report, company report or official report of Daiichi Sankyo.
• [7] JTT-553, a novel Acyl CoA:diacylglycerol acyltransferase (DGAT) 1 inhibitor, improves glucose metabolism in diet-induced obesity and genetic T2DM mice. J Pharmacol Sci. 2015 Sep;129(1):51-8.
• [8] Clinical pipeline report, company report or official report of Pfizer (2011).