AN363

AN363 is a small molecule drug candidate developed by Saniona, a biotechnology company specializing in ion channel-targeting therapeutics. It was designed as a subtype-selective positive allosteric modulator (PAM) of the GABA_A receptor, specifically targeting the alpha 2 (α2) and alpha 3 (α3) subunits. The primary therapeutic objective for AN363 was the treatment of neuropathic pain and chronic pruritus (itching). By selectively modulating the α2 and α3 subunits—which are primarily involved in pain and itch signaling in the spinal cord—AN363 aimed to provide relief without the sedative, cognitive, and addictive side effects associated with non-selective GABA_A modulators (such as benzodiazepines) that also activate the alpha 1 (α1) subunit. In 2016, Saniona paused the development of AN363 after observing unexpected toxicological findings in high-dose rat studies, which were not replicated in other animal models or seen with similar compounds. Consequently, the company transitioned its efforts to a second-generation backup candidate, SAN711, which demonstrated a superior safety profile in preclinical evaluations.