Diacylglycerol lipase α | Hydrolases | IUPHAR/BPS Guide to PHARMACOLOGY

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Diacylglycerol lipase α

Target not currently curated in GtoImmuPdb

Target id: 1396

Nomenclature: Diacylglycerol lipase α

Abbreviated Name: DAGLα

Family: Hydrolases, 2-Acylglycerol ester turnover

Annotation status:  image of an orange circle Annotated and awaiting review. Please contact us if you can help with reviewing.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 1042 11q12.3 DAGLA diacylglycerol lipase alpha
Mouse 4 1044 19 A Dagla diacylglycerol lipase, alpha
Rat 4 1044 1q43 Dagla diacylglycerol lipase, alpha
Previous and Unofficial Names
NAPE-hydrolyzing phospholipase D | FMP30 | NAPE-PLD | Neural stem cell-derived dendrite regulator | diacylglycerol lipase, alpha | diacylglycerol lipase
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 3.1.1.-
Endogenous substrates
diacylglycerol

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
Ligand Sp. Action Value Parameter Reference
DH376 Hs Inhibition 8.2 – 8.9 pIC50 3,7
pIC50 8.9 [3]
pIC50 8.2 [7]
DO34 Hs Inhibition 8.2 pIC50 7
pIC50 8.2 [7]
LEI105 Hs Inhibition 7.9 – 8.5 pIC50 1
pIC50 8.5 [1]
Description: Inhibition of recombinant human DAGα in a biochemical assay with para-nitrophenylbutyrate as a surrogate substrate.
pIC50 7.9 (IC50 1.3x10-8 M) [1]
orlistat Hs Inhibition 7.2 pIC50 2
pIC50 7.2 (IC50 6x10-8 M) [2]
KT-109 Hs Inhibition 5.6 pIC50 4
pIC50 5.6 (IC50 2.3x10-6 M) [4]
Description: Determined by competitive ABPP using the HT-01 probe for inhibition of recombinant human DAGL-α
RHC80267 Hs Inhibition 4.2 pIC50 5
pIC50 4.2 (IC50 6.5x10-5 M) [5]
Clinically-Relevant Mutations and Pathophysiology
Disease:  Spinocerebellar ataxia 20; SCA20
OMIM: 608687
Orphanet: ORPHA101110
References:  6

References

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1. Baggelaar MP, Chameau PJ, Kantae V, Hummel J, Hsu KL, Janssen F, van der Wel T, Soethoudt M, Deng H, den Dulk H et al.. (2015) Highly Selective, Reversible Inhibitor Identified by Comparative Chemoproteomics Modulates Diacylglycerol Lipase Activity in Neurons. J. Am. Chem. Soc., 137 (27): 8851-7. [PMID:26083464]

2. Bisogno T, Howell F, Williams G, Minassi A, Cascio MG, Ligresti A, Matias I, Schiano-Moriello A, Paul P, Williams EJ et al.. (2003) Cloning of the first sn1-DAG lipases points to the spatial and temporal regulation of endocannabinoid signaling in the brain. J. Cell Biol., 163 (3): 463-8. [PMID:14610053]

3. Deng H, Kooijman S, van den Nieuwendijk AM, Ogasawara D, van der Wel T, van Dalen F, Baggelaar MP, Janssen FJ, van den Berg RJ, den Dulk H et al.. (2017) Triazole Ureas Act as Diacylglycerol Lipase Inhibitors and Prevent Fasting-Induced Refeeding. J. Med. Chem., 60 (1): 428-440. [PMID:27992221]

4. Hsu KL, Tsuboi K, Adibekian A, Pugh H, Masuda K, Cravatt BF. (2012) DAGLĪ² inhibition perturbs a lipid network involved in macrophage inflammatory responses. Nat. Chem. Biol., 8 (12): 999-1007. [PMID:23103940]

5. Johnston M, Bhatt SR, Sikka S, Mercier RW, West JM, Makriyannis A, Gatley SJ, Duclos Jr RI. (2012) Assay and inhibition of diacylglycerol lipase activity. Bioorg. Med. Chem. Lett., 22 (14): 4585-92. [PMID:22738638]

6. Knight MA, Hernandez D, Diede SJ, Dauwerse HG, Rafferty I, van de Leemput J, Forrest SM, Gardner RJ, Storey E, van Ommen GJ et al.. (2008) A duplication at chromosome 11q12.2-11q12.3 is associated with spinocerebellar ataxia type 20. Hum. Mol. Genet., 17 (24): 3847-53. [PMID:18801880]

7. Ogasawara D, Deng H, Viader A, Baggelaar MP, Breman A, den Dulk H, van den Nieuwendijk AM, van den Nieuwendijk AM, Soethoudt M, van der Wel T et al.. (2016) Rapid and profound rewiring of brain lipid signaling networks by acute diacylglycerol lipase inhibition. Proc. Natl. Acad. Sci. U.S.A., 113 (1): 26-33. [PMID:26668358]

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