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Hello Bio/Clozapine N-oxide (CNO) (water soluble)/HB1807/5mg
Product overview
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NameClozapine N-oxide (CNO) (water soluble)
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Short descriptionWater soluble prototypical DREADD activator. Clozapine metabolite.
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Biological description
Clozapine N-oxide (CNO) is the prototypical chemical actuator for Gq- DREADDs. It is a metabolite of the atypical antipsychotic clozapine.
‘Excitatory’ Gq- coupled) DREADDs:CNO activates the excitatory Gq- coupled DREADDs: hM3Dq, hM1Dq and hM5Dq.
The hM3Dq DREADD is typically used for enhancing neuronal firing and activating (Gq- signaling in neuronal and non-neuronal cells.
‘Inhibitory’ (Gi- coupled) DREADDs:
CNO also activates the inhibitory hM4Di and hM2Di Gi-coupled DREADDs.
The hM4Di DREADD is the most commonly used inhibitory DREADD and is used for neuronal silencing.
Gs and β-arrestin coupled DREADDs:
CNO also activates the Gs- coupled DREADD (GsD) and the β-arrestin preferring DREADD: rM3Darr (Rq(R165L).
CNO can be administered intraperitoneally (i.p.), subcutaneously, directly infused intracranially, via drinking water or osmotic mini-pump. See our Technical review (table 3) for example administration methods and doses.
Recent findings suggest that systemically administered CNO does not readily cross the blood-brain-barrier in vivo, and converts to clozapine which activates DREADDs. Care must be taken in experimental design and proper controls should be incorporated. -
Alternative namesCNO
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Biological actionActivator
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Purity>98%
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Customer comments
Your technical review on CNO stability, solubility and use in the lab has been really helpful to my group. Verified customer
The Clozapine N-oxide (CNO) worked perfectly! It dissolved completely in saline at the dose I am using so no problems there! Verified customer, Istituto Italiano di Tecnologia
The clozapine N-oxide dissolves perfectly in saline, even at a high dose! Verified customer, Radboud University
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Properties
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Chemical name8-Chloro-11-(4-methyl-4-oxido-1-pip erazinyl)-5H-dibenzo[b,e][1,4]diazepine
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Molecular Weight342.82
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Chemical structure
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Molecular FormulaC18H19ClN4O
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CAS Number34233-69-7
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PubChem identifier2819
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SMILESC[N+]1(CCN(CC1)C2=C3C=CC=CC3=NC4=C(N2)C=C(C=C4)Cl)[O-]
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SourceSynthetic
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InChiInChI=1S/C18H19ClN4O/c1-23(24)10-8-22(9-11-23)18-14-4-2-3-5-15(14)20-16-7-6-13(19)12-17(16)21-18/h4-7,12,21H,8-11H2,1H3
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InChiKeyWYRDWWAASBTJLM-UHFFFAOYSA-N
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MDL numberMFCD00210190
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AppearanceYellow solid
Applications
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Application notes
Non-CNO DREADD activators- Compound 21 (DREADD agonist 21) hydrochloride has minimal off-target activity and is not metabolized to clozapine. The freebase Compound 21 (DREADD agonist 21) is also available.
- The potent and selective hM3Dq DREADD agonist Perlapine hydrochloride (water soluble) and Perlapine are also available.
- Salvinorin B (SALB) Salvinorin B (SALB) which potently activates the inhibitory KORD DREADD to induce neuronal inhibition is also available.
Storing and Using Your Product
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Storage instructionsRoom temperature (desiccate)
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Solubility overviewSoluble in water (100mM)
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Handling
During solubility testing, precipitation was found to occur in some concentrated (100mM) samples.
We therefore recommend making up solutions and using on same day if possible. Making and handling of solutions should be conducted in a dust free environment and ensure that product and solvents are at ambient temperature before use. Please take care to ensure that your product is completely dissolved before use. For more information, read our review Clozapine N-Oxide (water soluble) - a technical review on stability, solubility and use in the lab. It includes data on solubility, storage and handling, including results from our in-house tests, and guidelines on use in the lab, in vivo and in vitro.
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ImportantThis product is for RESEARCH USE ONLY and is not intended for therapeutic or diagnostic use. Not for human or veterinary use.
References for Clozapine N-oxide (CNO) (water soluble)
Novel designer receptors to probe GPCR signaling and physiology.
Wess et al (2013) Trends Pharmacol Sci. 34(7) : 385-92PubMedID: 23769625Evolving the lock to fit the key to create a family of G protein-coupled receptors potently activated by an inert ligand.
Arbruster et al (2007) Proc Natl Acad Sci U S A. 104(12) : 5163-8PubMedID: 17360345The role of M1 muscarinic receptor agonism of N-desmethylclozapine in the unique clinical effects of clozapine.
Weiner et al (2004) Psychopharmacology (Berl). 177(1-2) : 207-16PubMedID: 15258717A chemical-genetic approach to study G protein regulation of beta cell function in vivo.
Guettier et al (2009) Proc Natl Acad Sci U S A 106(45) : 19197-202PubMedID: https://www.ncbi.nlm.nih.gov/pub