|Name||JHU37152 dihydrochloride (DREADD ligand) (water soluble)|
|Description||Novel DREADD agonist with high affinity and potency for hM3Dq and hM4Di. Active in vivo. Water soluble.|
|Alternative names||J52 dihydrochloride|
|Biological description|| |
JHU37152 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 1.8 nM (hM3Dq) and 8.7 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.
JHU37152 activates hM3Dq and hM4Di with high potency and efficacy in fluorescent and BRET-based assays in HEK-293 cells (EC50 values are 5 and 0.5 nM at hM3Dq and hM4Di respectively.
JHU37152 exhibits high in vivo DREADD occupancy and was not reported to be a P-gp substrate.
In vivo application
JHU37152 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).
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.
Freebase also available.
Sold under license from the NIH, US patent pending 62/627,527
Solubility & Handling
|Solubility overview||Soluble in water (100mM). Always store solutions at -20°C.|
Storage of solid
Storage of solutions
|Handling continued..|| |
|Important||This product is for RESEARCH USE ONLY and is not intended for therapeutic or diagnostic use. Not for human or veterinary use|
|Chemical name||8-chloro-11-(4-ethylpiperazin-1-yl)-1-fluoro-5H-dibenzo[b,e][1,4]diazepine dihydrochloride|
|Molecular Formula||C19H20ClFN4 · 2HCl|
|CAS Number||2369979-67-7 (free base)|
|Licensing details||Sold under license from the NIH, US patent pending 62/627,527|
References for JHU37152 dihydrochloride (DREADD ligand) (water soluble)
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 ApneaCurado 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 graftsSubramanian 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 neurotheranosticsBonaventura et al (2018) bioRxiv : doi: https://doi.org/10.1101/487