MK-9470

Formula

C₂₉H₃₂FN₃O₃

Molar mass

489.60 g·mol⁻¹

CAS

947371-30-4

PubChem CID

11488705

Origin

A wholly synthetic compound. Its useful form is labelled with fluorine 18, a short-lived radionuclide produced in a cyclotron, which requires preparation within the hour preceding the examination and rules out any storage. It has no natural occurrence.

InChIKey

XIYPJXKEMLKFMD-HFZDXXHNSA-N

Editorial estimate, not clinical.

MK-9470 is the reference tracer for visualising the CB1 receptor in the human brain by positron emission tomography. Described in 2007 by Burns and colleagues, it is a selective inverse agonist of very high affinity, with a median inhibitory concentration of 0.7 nanomolar at the human receptor, labelled with fluorine 18. Its validation followed the complete approach expected of a radioligand. Autoradiography on macaque brain showed a distribution consistent with the established map of the receptor, dense in the cortex, the cerebellum, the basal ganglia, the substantia nigra and the hippocampus. Imaging in animals confirmed that distribution in vivo, with a ratio of total to non-specific binding of four to five in the putamen, a blockade of the signal by pretreatment with a potent inverse agonist and a displacement of already bound tracer, two criteria that establish specificity. In humans, the behaviour of the tracer proved very close to that observed in monkeys, with a reproducibility between two successive examinations of 7 per cent. The final demonstration concerned the expected use: oral administration of an inverse agonist under development produced a reduction of the signal proportional to the dose, that is a direct measure of receptor occupancy by the drug. The tracer subsequently served questions of human neurobiology, notably the demonstration of an increase in receptor availability with age, differing by sex, and the study of the receptor in chronic cannabis users.

An entirely chemical route, described here by class only. The molecule is an amide built around a propylamine skeleton linking a cyanophenyl to a phenyl bearing a fluoroethoxy chain, the whole being linked by the amide function to a methylpyridyloxy motif. Isotopic labelling consists in introducing fluorine 18 onto the ethoxy chain, an operation carried out in one step in the automated versions of the preparation.

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

Class

ECS modulator (research)

Origin

A wholly synthetic compound. Its useful form is labelled with fluorine 18, a short-lived radionuclide produced in a cyclotron, which requires preparation within the hour preceding the examination and rules out any storage. It has no natural occurrence.

Status

Unscheduled

1. 1.Burns et coll. 2007 : le [18F]MK-9470, traceur TEP du récepteur CB1 pour l'imagerie cérébrale humainePMID 17535893
2. 2.Van Laere et coll. 2008 : augmentation de la liaison au CB1 avec l'âge chez l'humain, dépendante du sexePMID 18077184
3. 3.Ceccarini et coll. 2015 : mesure par [18F]MK-9470 de la disponibilité du CB1 chez les consommateurs chroniques de cannabisPMID 24373053