Target Information

Target General Infomation
Target ID
T16688
Former ID
TTDS00466
Target Name
Diglyceride acyltransferase
Gene Name
DGAT1
Synonyms
ACAT-related gene product 1; AGRP1; DGAT; Diacylglycerol O-acyltransferase 1; DGAT1
Target Type
Successful
Disease Diabetes [ICD9: 253.5, 588.1; ICD10: E23.2, N25.1]
Familial chylomicronemia syndrome; HCV infection [ICD9:070.4, 070.5, 070.70; ICD10: J10, J11, B17.1, B18.2]
High cholesterol level [ICD9: 272; ICD10: E78.0]
Obesity; Diabetes [ICD9: 250, 278; ICD10: E08-E13, E66]
Obesity [ICD9: 278; ICD10: E66]
Type 2 diabetes [ICD9: 250; ICD10: E11]
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.
BioChemical Class
Acyltransferase
UniProt ID
O75907
EC Number
EC 2.3.1.76
Sequence
MGDRGSSRRRRTGSRPSSHGGGGPAAAEEEVRDAAAGPDVGAAGDAPAPAPNKDGDAGVG
SGHWELRCHRLQDSLFSSDSGFSNYRGILNWCVVMLILSNARLFLENLIKYGILVDPIQV
VSLFLKDPYSWPAPCLVIAANVFAVAAFQVEKRLAVGALTEQAGLLLHVANLATILCFPA
AVVLLVESITPVGSLLALMAHTILFLKLFSYRDVNSWCRRARAKAASAGKKASSAAAPHT
VSYPDNLTYRDLYYFLFAPTLCYELNFPRSPRIRKRFLLRRILEMLFFTQLQVGLIQQWM
VPTIQNSMKPFKDMDYSRIIERLLKLAVPNHLIWLIFFYWLFHSCLNAVAELMQFGDREF
YRDWWNSESVTYFWQNWNIPVHKWCIRHFYKPMLRRGSSKWMARTGVFLASAFFHEYLVS
VPLRMFRLWAFTGMMAQIPLAWFVGRFFQGNYGNAAVWLSLIIGQPIAVLMYVHDYYVLN
YEAPAAEA
Drugs and Mode of Action
Drug(s) Hesperetin Drug Info Approved High cholesterol level [552004]
LCQ908 Drug Info Phase 3 Familial chylomicronemia syndrome; HCV infection [523768], [542776]
AZD7687 Drug Info Phase 1 Obesity; Diabetes [542772], [550290]
P-7435 Drug Info Phase 1 Diabetes [524180]
DS-7250 Drug Info Discontinued in Phase 1 Diabetes [549362]
JTT-553 Drug Info Discontinued in Phase 1 Obesity [548598]
PF-04620110 Drug Info Terminated Type 2 diabetes [542774], [551489]
Inhibitor AZD7687 Drug Info [550290]
Hesperetin Drug Info [535956]
JTT-553 Drug Info [533317]
P-7435 Drug Info [549156]
PF-04620110 Drug Info [551489]
Modulator DS-7250 Drug Info [550585]
LCQ908 Drug Info [531007]
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
BioCyc Pathway Triacylglycerol biosynthesis
KEGG Pathway Glycerolipid metabolism
Retinol metabolism
Metabolic pathways
Fat digestion and absorption
PathWhiz Pathway Retinol Metabolism
Reactome Acyl chain remodeling of DAG and TAG
Triglyceride Biosynthesis
WikiPathways Vitamin A and Carotenoid Metabolism
Statin Pathway
Triacylglyceride Synthesis
Glycerophospholipid biosynthesis
Fatty acid, triacylglycerol, and ketone body metabolism
References
Ref 523768ClinicalTrials.gov (NCT01514461) A Randomized, Double-blind, Placebo Controlled Study to Assess Efficacy, Safety and Tolerability of LCQ908 in Subjects With Familial Chylomicronemia Syndrome. U.S. National Institutes of Health.
Ref 524180ClinicalTrials.gov (NCT01764425) Clinical Trial to Study the Safety Tolerability, Pharmacokinetics, Food Effect & Pharmacodynamics of a New Compound P7435 in Healthy, Overweight and/or Obese Subjects. U.S. National Institutes of Health.
Ref 542772(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. (Ligand id: 7827).
Ref 542774(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. (Ligand id: 7829).
Ref 542776(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. (Ligand id: 7830).
Ref 548598Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800026874)
Ref 549362Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800035670)
Ref 550290Clinical pipeline report, company report or official report of AstraZeneca (2011).
Ref 551489Clinical pipeline report, company report or official report of Pfizer (2011).
Ref 552004Drug information of Hesperetin, 2008. eduDrugs.
Ref 531007DGAT1 inhibitors as anti-obesity and anti-diabetic agents. Curr Opin Drug Discov Devel. 2010 Jul;13(4):489-96.
Ref 533317JTT-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.
Ref 535956In vitro inhibition of diacylglycerol acyltransferase by prenylflavonoids from Sophora flavescens. Planta Med. 2004 Mar;70(3):258-60.
Ref 549156Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800033014)
Ref 550290Clinical pipeline report, company report or official report of AstraZeneca (2011).
Ref 550585Clinical pipeline report, company report or official report of Daiichi Sankyo.
Ref 551489Clinical pipeline report, company report or official report of Pfizer (2011).

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