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DH376

A laboratory probe that blocks 2-AG production (a diacylglycerol lipase inhibitor).

Level of detail

Harm-reduction warning

No characterised human dose: animal / in vitro data only. Effect profile, safety margin and acute toxicity are not documented in human clinical practice. Extremely potent compound: severe effects, seizures and deaths reported in the literature.

C₃₁H₂₈F₂N₄O₃

CID 129188688

Family
ECS pharmacological toolEnzyme inhibitor
Molar mass
542.60 g/mol

Updated on

In plain terms

DH376 is a laboratory molecule, not a cannabinoid from hemp. It blocks the enzyme that makes 2-AG, a substance the body produces itself and that acts on the same receptors as THC. Researchers use it on cells and in animals to understand the role of this signal; it is not a consumer product.

Receptors and activity

Target network

  • Blocks or inhibits

The lower the cited value, the closer the target sits to DH376: one ring per factor of 100. A target with no measured value stays on the edge.

Cited values

  1. DAGLαInhibitorIC50 = 6 nM · human70 out of 100

    Ogasawara et al., PNAS 2016 (new tab) · recombinant human DAGLα (HEK293T cell lysates), conversion of the SAG substrate to 2-AG; 0.5 to 1.2 nM in ABPP profiling

  2. DAGLβInhibitorno measured value cited
  3. ABHD6Inhibitorno measured value cited
  4. PLA2G7Inhibitorno measured value cited
Bar length follows the measured value (Ki, Kd, EC50 or IC50), on one scale shared by every entry, from 100 µM to 0.1 nM. A target with no cited value has no bar.

Pharmacology

DH376 is a 1,2,3-triazole urea, a chemical probe of the endocannabinoid system that covalently and irreversibly inhibits diacylglycerol lipases α and β, the enzymes that synthesise 2-AG (Ogasawara et al. 2016). Its IC50 is 6 nM on recombinant human DAGLα and 3 to 8 nM on DAGLβ. In mice, intraperitoneal injection of 3 to 50 mg/kg blocked brain DAGLα activity in a dose-dependent manner (ED50 of 5 to 10 mg/kg, full inhibition at 30-50 mg/kg), with inhibition lasting up to 8 h at 50 mg/kg and partial recovery at 24 h. Within 2 h, DAGL blockade reorganised bioactive brain lipids (higher diacylglycerols, lower 2-AG, anandamide, arachidonic acid and the prostaglandins PGD2 and PGE2), abolished most of two CB1-dependent forms of synaptic plasticity in brain slices (cerebellar DSE and hippocampal DSI) and attenuated lipopolysaccharide-induced anapyrexia. Deng et al. (2017) describe the molecule as a picomolar-activity inhibitor; in fasted mice it temporarily reduced refeeding, as did DO34 but also the control DO53, which does not inhibit DAGLs: the authors conclude that triazole ureas may affect energy balance through several targets. All these data are preclinical.

History

Source
A synthetic molecule of the 1,2,3-triazole urea class, absent from cannabis and from any living organism. A chemical probe distributed as a research reagent.

Origin

Research tool

No biosynthetic pathway: a synthetic molecule of the 1,2,3-triazole urea class.

Classification

Family, origin and source verification

Family

ECS pharmacological tool › Enzyme inhibitor

Verification

Classification, sources and binding values checked on 20 October 2026; text read against its sources and Wikipedia.

Wikipedia (English)

No dedicated article.

References

Identifiers

Names

IUPAC name
[(2R,5R)-2-benzyl-5-prop-2-ynoxypiperidin-1-yl]-[4-[bis(4-fluorophenyl)-hydroxymethyl]triazol-2-yl]methanone
Other names
DH-376

Identifiers

Formula
C₃₁H₂₈F₂N₄O₃
InChIKey
GVLOFRPVRYAFKI-VSGBNLITSA-N
SMILES
C#CCO[C@@H]1CC[C@@H](N(C1)C(=O)N2N=CC(=N2)C(C3=CC=C(C=C3)F)(C4=CC=C(C=C4)F)O)CC5=CC=CC=C5

Machine-readable entry (JSON)

LLM ingestion format: a structured superset of the entry (identifiers, binding, versioned legal status). Full corpus.