While G-protein coupled receptors (GPCRs) have shown to be one of the most successful classes of druggable targets in the human genome—with estimates ranging between 30-50% of all medications targeting this class—there remains a vast array of specific targets within the GPCR class that needs to be elucidated. More recently, GPCRs have been shown to be modifiable so that they only respond to a specific biologically inert chemical (designer drug).
These modified GPCRs are have been dubbed by investigators as designer receptors exclusively activated by designer drugs (DREADDs). Cells expressing DREADDs respond robustly to low concentrations of the designer molecule, whereas cells that do not express DREADDs are unresponsive to the designer drug. Moreover, DREADDs have been used ubiquitously to modulate GPCR activity noninvasively in vivo.
Now, Hello Bio, a U.K. based life sciences company has recently launched a new addition to its growing catalog of biomolecules called Compound 21, which is a water soluble DREADD agonist. Compound 21 is a useful alternative clozapine N-oxide (CNO), which has broad biological activity, often making it difficult to measure targeted responses. Recent publications have reported that the traditionally used DREADD agonist CNO may have more off-target effects in vivo than previously thought. Therefore, pharmacological tools that offer additional ways to investigate DREADDs are extreme value to researchers in this field.
“Water-soluble Compound 21 (DREADD agonist 21) can be used as an alternative to clozapine N-oxide (water soluble), or to supplement CNO studies,” noted Steve Roome Ph.D., managing director and founder of Hello Bio. “Compound 21 has a similar in vivo potency to CNO but is less likely to metabolize to clozapine. It offers another option for researchers studying DREADDs.”
Water soluble Compound 21 (DREADD agonist 21) joins a range of affordable and high-quality tools for GPCR and DREADDs research, including DREADD ligands clozapine N-oxide and salvinorin B, and the novel GRK2/3 inhibitor Cmpd101, that can be used to study GPCR desensitization.