Product overview

Name JHU37160 (DREADD ligand)
Description Novel DREADD agonist with high affinity and potency for hM3Dq and hM4Di. Active in vivo. Freebase.
Alternative names J60
Purity >98%
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JHU37160 (DREADD ligand) product vial image | Hello Bio

Biological Data

Biological description

Overview

JHU37160 is reported to be a novel DREADD agonist with high in vivo DREADD potency for CNS applications.

It has high affinity in vitro for hM3Dq and hM4Di (Ki values are 1.9 nM (hM3Dq) and 3.6 nM (hM4Di).

It selectively displaces [3H]clozapine from DREADDs and not from other clozapine-binding sites at concentrations up to 10 nM when tested for in situ [3H]clozapine displacement in brain tissue from WT and D1-DREADD mice.

JHU37160 activates hM3Dq and hM4Di with high potency and efficacy in fluorescent and BRET-based assays in HEK-293 cells (EC50 values are 18.5 and 0.2 nM at hM3Dq and hM4Di respectively.

Occupancy

JHU37160 exhibits high in vivo DREADD occupancy and was not reported to be a P-gp substrate.

In vivo application

JHU37160 is reported to be a potent in vivo DREADD agonist, which selectively inhibits locomotor activity in D1-hM3Dq and D1-hM4Di mice without any significant locomotor effects observed in wild type (WT) mice (at doses ranging 0.01 - 1 mg/kg).

It also produces robust and selective increases in hM3Dq-stimulated locomotion in rats expressing hM3Dq in tyrosine hydroxylase expressing neurons (at doses ranging 0.01 – 0.3 mg/kg).

In in vivo electrophysiology experiments in mice, JHU37160 produces rapid and potent hM4Di-driven inhibition of light-evoked neuronal activation (at a dose of 0.1 mg/kg).

While its selectivity is not ideal (i.e. comparable to clozapine), its high in vivo potency allows for dose adjustments with minimal off-target effects. The compound exhibits promising characteristics for DREADD use in monkeys.

Water soluble version also available.

Sold under license from the NIH, US patent pending 62/627,527

Solubility & Handling

Storage instructions Room temperature
Solubility overview Soluble in DMSO (100 mM)
Important This product is for RESEARCH USE ONLY and is not intended for therapeutic or diagnostic use. Not for human or veterinary use

Calculators

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Chemical Data

Chemical name 8-chloro-11-(4-ethylpiperazin-1-yl)-4-fluoro-5H-dibenzo[b,e][1,4]diazepine
Molecular Weight 358.84
Chemical structure JHU37160 | Hello Bio Chemical Structure
Molecular Formula C19H20ClFN4
CAS Number 2369979-68-8
SMILES CCN1CCN(CC1)C3=Nc4cc(Cl)ccc4Nc2c3cccc2F
Source Synthetic
InChi InChI=1S/C19H20ClFN4/c1-2-24-8-10-25(11-9-24)19-14-4-3-5-15(21)18(14)22-16-7-6-13(20)12-17(16)23-19/h3-7,12,22H,2,8-11H2,1H3
InChiKey SWSCWOSASZXIRK-UHFFFAOYSA-N
Appearance Yellow solid
Licensing details Sold under license from the NIH, US patent pending 62/627,527

References for JHU37160 (DREADD ligand)

References are publications that support the biological activity of the product
  • High-potency ligands for DREADD imaging and activation in rodents and monkeys.

    Bonaventura et al (2019) Nat Commun. 10(1) : 4627
  • 0067 Humanized Chemogenetic Approach to Treat Sleep Apnea

    Curado et al (2019) Sleep (42) : A28
  • OP-01-02 Graft-host synaptic connectivity can be chemogenetically inhibited with clinically relevant activators to eliminate graft-induced dyskinesias (GID) without loosing anti-parkinsonian benefits of dopaminergic grafts

    Subramanian et al (2019) World Congress On Parkinson's Disease And Related Disorders 2019 : Poster Abstract
  • DREADDs: The Power of the Lock, the Weakness of the Key. Favoring the Pursuit of Specific Conditions Rather than Specific Ligands.

    Goutaudier et al (2019) eNeuro 6 : (5)
  • Chemogenetic ligands for translational neurotheranostics

    Bonaventura et al (2018) bioRxiv : doi: https://doi.org/10.1101/487