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Water soluble DREADD ligands: only available from Hello Bio

Water soluble DREADD ligands: only available from Hello Bio
By Sam Roome 2 years ago 2144 Views No comments

DREADDs are an increasingly popular field, but the pharmacological tools and ligands available have not been readily water soluble. Researchers have had to use DMSO or ethanol to solubilise them - which is not ideal for studies in biological systems. In response to scientists requests, our team of chemists have been hard at work to manufacture a range of DREADD ligands that are water soluble - many of which are only available from Hello Bio. They've been reviewed and rated by researchers too - find out more...

Perlapine dihydrochloride

Perlapine is a novel, potent and selective hM3Dq DREADD receptor agonist. Perlapine shows high potency (EC50 = 2.8 nM) for hM3Dq and displays >10,000-fold selectivity for hM3Dq over hM3 muscarinic receptors. It also activates the inhibitory hM2Di and hM4Di Gi-DREADDs.

Unlike CNO, perlapine is especially suited for translational studies.

The dihydrochloride salt of perlapine is water soluble and is only available from Hello Bio.


Compound 21 (DREADD agonist 21) dihydrochloride

Compound 21 (DREADD agonist 21) is an analog of CNO, and has been suggested to be a useful alternative to CNO.

It is a highly potent agonist at the excitatory hM3Dq DREADD (EC50 = 1.7 nM) and shows high selectivity for activating hM3Dq compared to the native hM3 muscarinic receptor and other GPCRs. There are indications that Compound 21 cannot be metabolized via normal routes to clozapine (or any related compound), has minimal off-target activity and has equivalent potency in vivo when compared with clozapine N-oxide (CNO).

The Michaelides group presented a poster at SfN2017 indicating that Compound 21 has lower binding affinity for DREADDs compared to clozapine and that Compound 21 induces behavioural effects in transgenic mice.

The dihydrochloride salt of Compound 21 is water soluble - and only available from Hello Bio!


Clozapine dihydrochloride

Clozapine has been used by researchers for some years - it is an atypical antipsychotic that binds to both serotonin and dopamine receptors in the brain. It is also of interest to the DREADDs community – the DREADD ligand CNO is metabolised to clozapine, and recent reports suggest that clozapine itself may have high affinity and potency for DREADDs.

But - up until now, it has only been commercially available in a form that is sparingly water-soluble – and researchers have had to use DMSO or ethanol to solubilise it, which isn't the best option for biological studies.

Hello Bio has now manufactured the dihydrochloride salt of clozapine and this is readily soluble in water (to a concentration of 100 mM). This offers researchers a more flexible and adaptable tool, enabling them to use water as their solvent. It's also been rated 5* by researchers from UTHSC!


Clozapine N-oxide dihydrochloride

Clozapine N-oxide dihydrochloride (CNO) is the dihydrochloride salt of CNO, which is the prototypical chemical DREADDs activator. It is a metabolite of clozapine.

CNO activates the excitatory Gq- coupled DREADDs: hM3Dq, hM1Dq and hM5Dq and the inhibitory hM4Di and hM2Di Gi-coupled DREADDs. CNO also activates the Gs- coupled DREADD (GsD) and the β-arrestin preferring DREADD: rM3Darr (Rq(R165L).

Recent findings suggest that systemically administered CNO does not readily cross the blood-brain-barrier in vivo, and converts to clozapine which activates DREADDs. So care must be taken in experimental design and proper controls should be incorporated into your experiments.

CNO dihydrochloride is water soluble. Although available from other suppliers, we have carried out in-depth stability studies on this product and have shown that our CNO dihydrochloride is easier to solubilize and handle, and is more stable in solution than the freebase form of CNO (which, due to its inherent chemical properties requires careful handling and has been shown in the literature to precipitate in solution under certain conditions). Our CNO dihydrochloride has also been rated 5* by researchers from UTHSC!

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If these products have piqued your interest into DREADDs, you can view our full DREADDs range here to see what else is available in this field, or read our mini-review.