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Gene and Protein Information  |
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| Species | TM | AA | Chromosomal Location | Gene Symbol | Gene Name | Reference |
| Human | 3 | 488 | 8q24.3 | DGAT1 | diacylglycerol O-acyltransferase 1 | |
| Mouse | 3 | 498 | 15 35.99 cM | Dgat1 | diacylglycerol O-acyltransferase 1 | |
| Rat | 3 | 498 | 7q34 | Dgat1 | diacylglycerol O-acyltransferase 1 | |
| Previous and Unofficial Names |
| ARGP1 | DGAT |
| Database Links |
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| Alphafold | O75907 (Hs), Q9Z2A7 (Mm), Q9ERM3 (Rn) |
| BRENDA | 2.3.1.20 |
| ChEMBL Target | CHEMBL6009 (Hs), CHEMBL1075284 (Mm), CHEMBL6129 (Rn) |
| Ensembl Gene | ENSG00000185000 (Hs), ENSMUSG00000022555 (Mm), ENSRNOG00000028711 (Rn) |
| Entrez Gene | 8694 (Hs), 13350 (Mm), 84497 (Rn) |
| Human Protein Atlas | ENSG00000185000 (Hs) |
| KEGG Enzyme | 2.3.1.20 |
| KEGG Gene | hsa:8694 (Hs), mmu:13350 (Mm), rno:84497 (Rn) |
| OMIM | 604900 (Hs) |
| Pharos | O75907 (Hs) |
| RefSeq Nucleotide | NM_012079 (Hs), NM_010046 (Mm), NM_053437 (Rn) |
| RefSeq Protein | NP_036211 (Hs), NP_034176 (Mm), NP_445889 (Rn) |
| UniProtKB | O75907 (Hs), Q9Z2A7 (Mm), Q9ERM3 (Rn) |
| Wikipedia | DGAT1 (Hs) |
| Enzyme Reaction |
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Download all structure-activity data for this target as a CSV file 
| Inhibitors | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Key to terms and symbols | View all chemical structures | Click column headers to sort | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Immuno Process Associations | ||
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| Clinically-Relevant Mutations and Pathophysiology
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| General Comments |
| DGAT1 catalyzes the final committed step in triglyceride synthesis and is believed to play a key role in whole body energy homeostasis [6]. Inhibition of DGAT1 represents a novel approach to treat metabolic disease and obesity [5,12] and as such has become the focus of intense interest from the pharmaceutical industry [3-4,8,11]. Their efforts have lead to the development of many novel DGAT1 inhibitors, some of which are reaching the clinic. Unfortunately many of the lead compounds are associated with adverse gastrointestinal events [7], so medicinal chemists are working to elucidate the underlying mechanism to develop novel compounds which will circumvent this undesireable action. |
1. Barlind JG, Bauer UA, Birch AM, Birtles S, Buckett LK, Butlin RJ, Davies RD, Eriksson JW, Hammond CD, Hovland R et al.. (2012) Design and optimization of pyrazinecarboxamide-based inhibitors of diacylglycerol acyltransferase 1 (DGAT1) leading to a clinical candidate dimethylpyrazinecarboxamide phenylcyclohexylacetic acid (AZD7687). J Med Chem, 55 (23): 10610-29. [PMID:23116186]
2. Birch AM, Birtles S, Buckett LK, Kemmitt PD, Smith GJ, Smith TJ, Turnbull AV, Wang SJ. (2009) Discovery of a potent, selective, and orally efficacious pyrimidinooxazinyl bicyclooctaneacetic acid diacylglycerol acyltransferase-1 inhibitor. J Med Chem, 52 (6): 1558-68. [PMID:19256504]
3. Birch AM, Buckett LK, Turnbull AV. (2010) DGAT1 inhibitors as anti-obesity and anti-diabetic agents. Curr Opin Drug Discov Devel, 13 (4): 489-96. [PMID:20597032]
4. Cao J, Zhou Y, Peng H, Huang X, Stahler S, Suri V, Qadri A, Gareski T, Jones J, Hahm S et al.. (2011) Targeting Acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) with small molecule inhibitors for the treatment of metabolic diseases. J Biol Chem, 286 (48): 41838-51. [PMID:21990351]
5. Chen HC, Farese Jr RV. (2000) DGAT and triglyceride synthesis: a new target for obesity treatment?. Trends Cardiovasc Med, 10 (5): 188-92. [PMID:11282293]
6. Cheng D, Iqbal J, Devenny J, Chu CH, Chen L, Dong J, Seethala R, Keim WJ, Azzara AV, Lawrence RM et al.. (2008) Acylation of acylglycerols by acyl coenzyme A:diacylglycerol acyltransferase 1 (DGAT1). Functional importance of DGAT1 in the intestinal fat absorption. J Biol Chem, 283 (44): 29802-11. [PMID:18768481]
7. Denison H, Nilsson C, Löfgren L, Himmelmann A, Mårtensson G, Knutsson M, Al-Shurbaji A, Tornqvist H, Eriksson JW. (2014) Diacylglycerol acyltransferase 1 inhibition with AZD7687 alters lipid handling and hormone secretion in the gut with intolerable side effects: a randomized clinical trial. Diabetes Obes Metab, 16 (4): 334-43. [PMID:24118885]
8. DeVita RJ, Pinto S. (2013) Current status of the research and development of diacylglycerol O-acyltransferase 1 (DGAT1) inhibitors. J Med Chem, 56 (24): 9820-5. [PMID:23919406]
9. Dow RL, Li JC, Pence MP, Gibbs EM, LaPerle JL, Litchfield J, Piotrowski DW, Munchhof MJ, Manion TB, Zavadoski WJ et al.. (2011) Discovery of PF-04620110, a Potent, Selective, and Orally Bioavailable Inhibitor of DGAT-1. ACS Med Chem Lett, 2 (5): 407-12. [PMID:24900321]
10. He S, Hong Q, Lai Z, Yang DX, Ting PC, Kuethe JT, Cernak TA, Dykstra KD, Sperbeck DM, Wu Z et al.. (2014) Discovery of a Potent and Selective DGAT1 Inhibitor with a Piperidinyl-oxy-cyclohexanecarboxylic Acid Moiety. ACS Med Chem Lett, 5 (10): 1082-7. [PMID:25349648]
11. Zammit VA, Buckett LK, Turnbull AV, Wure H, Proven A. (2008) Diacylglycerol acyltransferases: Potential roles as pharmacological targets. Pharmacol Ther, 118 (3): 295-302. [PMID:18508126]
12. Zhao G, Souers AJ, Voorbach M, Falls HD, Droz B, Brodjian S, Lau YY, Iyengar RR, Gao J, Judd AS et al.. (2008) Validation of diacyl glycerolacyltransferase I as a novel target for the treatment of obesity and dyslipidemia using a potent and selective small molecule inhibitor. J Med Chem, 51 (3): 380-3. [PMID:18183944]
13. Zhou G, Zorn N, Ting P, Aslanian R, Lin M, Cook J, Lachowicz J, Lin A, Smith M, Hwa J et al.. (2014) Development of novel benzomorpholine class of diacylglycerol acyltransferase I inhibitors. ACS Med Chem Lett, 5 (5): 544-9. [PMID:24900877]
2.3.1.- Acyltransferases: diacylglycerol O-acyltransferase 1. Last modified on 13/08/2015. Accessed on 18/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2821.
