IDFPIsopropyl dodecylfluorophosphonate

Formula

C₁₅H₃₂FO₂P

Molar mass

294.40 g·mol⁻¹

CAS

615250-02-7

PubChem CID

24762154

Origin

A wholly synthetic compound with no natural occurrence. It is produced as a research reagent in toxicology and pharmacology, and has no human, agricultural or veterinary use.

InChIKey

SFRALHFBKRAJPW-UHFFFAOYSA-N

Editorial estimate, not clinical.

Isopropyl dodecylfluorophosphonate holds a particular place in the endocannabinoid literature because it entered it not through pharmacology but through toxicology. It arose from a programme by Casida and his colleagues on the secondary targets of organophosphorus compounds, whose toxicity had been attributed solely to inhibition of acetylcholinesterase. The work showed that a suitably chosen fatty chain directs the fluorophosphonate towards the lipases rather than towards the cholinesterase, and this compound is its clearest illustration: it jointly inhibits monoacylglycerol lipase and fatty acid amide hydrolase, the two enzymes that govern the lifetime of 2-arachidonoylglycerol and anandamide, while leaving brain acetylcholinesterase practically intact. In mice, that dual inhibition massively raises brain endocannabinoids and produces a behavioural set dependent on cannabinoid receptors, which made it the tool of choice for studying what a saturation of the system entails. The reach of the result goes beyond the endocannabinoid field. Suzuki and colleagues used the compound as a reference comparator to show that a commonly used organophosphorus insecticide, fenitrothion, likewise induces plasma hypertriglyceridaemia by preferential inhibition of the amide hydrolase; the anomaly was prevented by a cannabinoid receptor antagonist, which does tie it to an overstimulation of endocannabinoid signalling. That body of evidence designates the endocannabinoid system as an unintended target of organophosphorus compounds and a plausible mechanism of their metabolic effects.

An entirely chemical route, described here by class only. The molecule combines a saturated twelve-carbon dodecyl chain, which ensures recognition by the lipases, with a fluorophosphonate head esterified by an isopropyl group. It belongs to the same strategy as the other organophosphorus lipase inhibitors, where the fatty chain directs the electrophile towards the active site of the target enzyme.

Sources: EUR-Lex, UNODC, CND, ANSM, IUPHAR/BPS, ChEBI, EUDA. Our method.

Class

ECS modulator (research)

Origin

A wholly synthetic compound with no natural occurrence. It is produced as a research reagent in toxicology and pharmacology, and has no human, agricultural or veterinary use.

Status

Unscheduled

1. 1.Casida et coll. 2008 : lipases sensibles aux organophosphorés et modulation des endocannabinoïdes cérébrauxPMID 18495101
2. 2.Suzuki et coll. 2014 : hypertriglycéridémie induite par les organophosphorés via l'inhibition des hydrolases des endocannabinoïdesPMID 24361246