PDE4 inhibitor

BPN14770, now named zatolmilast, is an oral drug candidate from Tetra Therapeutics, a Shionogi subsidiary. It is an allosteric inhibitor of phosphodiesterase-4D (PDE4D), built to raise cAMP signalling in neurons without the vomiting that has stalled other PDE4 inhibitors. In mice carrying the human form of the enzyme it improved memory at oral doses of 0.01–0.03 mg/kg, and a 30-man crossover trial in fragile X syndrome reported gains in language-related cognition. The larger trials have not confirmed it. A 255-patient phase 2 trial in early Alzheimer's disease found no difference from placebo, and in May 2026 Shionogi reported that both phase 3 trials in fragile X syndrome had missed their primary endpoints.