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Research tools

JNJ-42165279

A covalent FAAH inhibitor (Janssen): primary endpoint not met in four phase 2 trials.

Unscheduled
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.

C₁₈H₁₇ClF₂N₄O₃

CAS 1346528-50-4

Family
ECS pharmacological toolEnzyme inhibitor
Molar mass
410.80 g/mol

Updated on

In plain terms

JNJ-42165279 is a laboratory molecule developed by a pharmaceutical group, with no link to hemp. It blocks an enzyme in the body that destroys the cannabinoids the body makes itself, which raises their level. Tested in social anxiety, depression with anxious distress, autism and post-traumatic stress, it met the primary endpoint of none of these trials and is sold nowhere.

Receptors and activity

Target network

FAAHInhibitorno measured value
  • Blocks or inhibits

The lower the cited value, the closer the target sits to JNJ-42165279: one ring per factor of 100. A target with no measured value stays on the edge.

Where these targets live

Where each target has been found in humans, according to the cited studies. The map shows the target, not an effect of JNJ-42165279.

Brain, side view
Body, front view
Blood

FAAHFAAH found in 7 regions of the body

  1. CortexpresentCortical pyramidal neurons1
  2. Basal gangliapresentStriatal neurons1
  3. HypothalamuspresentPresent in hypothalamic nuclei1
  4. CerebellumpresentPurkinje cells and cerebellar layers1
  5. BrainstempresentInferior olivary nuclei1
  6. Adipose tissuepresentExpressed in mature adipocytes2
  7. BonepresentPresent on osteoclasts3

Map sources

  1. Romero J et al. Fatty acid amide hydrolase localization in the human central nervous system: an immunohistochemical study. Brain Res Mol Brain Res, 2002 (new tab)
  2. Engeli S et al. Activation of the peripheral endocannabinoid system in human obesity. Diabetes, 2005 (new tab)
  3. Rossi F et al. The endovanilloid/endocannabinoid system in human osteoclasts: possible involvement in bone formation and resorption. Bone, 2009 (new tab)

Cited values

  1. FAAHInhibitorno measured value cited
  2. CYP2D6Inhibitorno 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

JNJ-42165279 is not a cannabinoid: it is an arylpiperazinyl urea that covalently inactivates FAAH (fatty acid amide hydrolase), the enzyme that hydrolyses anandamide, oleoylethanolamide and palmitoylethanolamide, and it is highly selective against the other targets tested (Keith et al. 2015). In healthy volunteers, positron emission tomography shows near-complete occupancy of brain FAAH from 10 mg, still above 80% about 24 hours after a 10 mg dose is stopped; plasma anandamide rose 5.5- to 10-fold and cerebrospinal fluid anandamide 41- to 77-fold depending on the dose (Postnov et al. 2018). The target is therefore reached, but clinical benefit does not follow: in social anxiety (149 subjects), the change in the LSAS score, the primary endpoint, did not differ significantly from placebo (−29.4 against −22.4), although the proportion of responders was higher on treatment (42.4% against 23.6%) (Schmidt et al. 2021); in major depression with anxious distress (153 participants), the primary endpoint was not met (Schmidt et al. 2026); in autism spectrum disorder (61 participants analysed), the three primary endpoints were not met (Klein et al. 2024); in post-traumatic stress disorder (100 patients), no effect on symptoms was seen (Mayo et al. 2025). No therapeutic effect is established in humans.

Key sources.

History

Source
A wholly synthetic molecule, with no known natural occurrence. It was designed by Janssen Research & Development (Johnson & Johnson group) within a series of arylpiperazine ureas intended for FAAH inhibition. It has never been marketed and exists only in preclinical research and in clinical trials.

Origin

Research tool

No biological pathway: the molecule comes from no living organism and has nothing to do with the biosynthesis of hemp cannabinoids. It is obtained by organic synthesis, in the class of arylpiperazine ureas, by combining a 2,2-difluoro-1,3-benzodioxole motif with a 4-chloropyridin-3-ylamine.

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)

JNJ-42165279 (new tab)

Article paired by the molecule's structure (InChIKey), revision read on 19 October 2026. Read as a second opinion, never cited as a source.

References

  1. Keith JM et al., ACS Med Chem Lett 2015: preclinical characterisation of JNJ-42165279 (new tab)PMID 26713105
  2. Postnov A et al., Clin Transl Sci 2018: repeated doses and positron emission tomography in healthy volunteers (new tab)PMID 29575526
  3. Schmidt ME et al., Neuropsychopharmacology 2021: social anxiety (new tab)PMID 33070154
  4. Klein ME et al., Neuropsychopharmacology 2024: autism spectrum disorder (new tab)PMID 39414987
  5. Mayo LM et al., Neuropsychopharmacology 2025: post-traumatic stress disorder (new tab)PMID 40382500
  6. Schmidt ME et al., Eur Neuropsychopharmacol 2026: major depression with anxious distress (new tab)PMID 41616640
  7. van Heerden M et al., Toxicol Pathol 2021: nuclear cataracts in the rat (new tab)PMID 34128434
  8. Heins MS et al., Neurochem Int 2025: JNJ-42165279 selectively raises anandamide in the rat amygdala (new tab)PMID 40494414
  9. ChEMBL, compound CHEMBL4297294 (JNJ-42165279): IC50 for FAAH and CYP2D6 (new tab)
  10. PubChem, compound record CID 54576693 (JNJ-42165279) (new tab)

Identifiers

Names

IUPAC name
N-(4-chloro-3-pyridinyl)-4-[(2,2-difluoro-1,3-benzodioxol-5-yl)methyl]piperazine-1-carboxamide
Other names
JNJ42165279 · JNJ 42165279

Identifiers

Formula
C₁₈H₁₇ClF₂N₄O₃
CAS
1346528-50-4
PubChem CID
54576693(new tab)
InChIKey
YWGYNGCRVZLMCS-UHFFFAOYSA-N
SMILES
C1CN(CCN1CC2=CC3=C(C=C2)OC(O3)(F)F)C(=O)NC4=C(C=CN=C4)Cl

Machine-readable entry (JSON)

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