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molecules of the month

difamilast

topical PDE4 inhibitor

marketed in Japan

PDE4B subtype-selective inhibitor; discovery not disclosed

JPET, April 11, 2023

Otsuka, Tokyo, JP

difamilast,PDE4B, topical PDE4 inhibitor, marketed in Japan PDE4B subtype-selective inhibitor; discovery not disclosed, JPET, April 11, 2023, OTSUKA, TOKYO, JP
5 mins read

Difamilast is a selective, topical PDE4B inhibitor avoiding GI side effects. PDE4 inhibitors have shown promise in a range of pulmonary, dermatological and neurological diseases, but have been hampered by side effects including emesis and diarrhea. Difamilast, originated by Otsuka, recently approved for the treatment of atopic dermatitis (AD) in Japan (September, 2021), selectively inhibits the PDE4B subtype relative to the emesis-causing PDE4D subtype and has restricted systemic and brain exposure through its topical application. Up to 20% of children and 5% of adults suffer from AD, with topical corticosteroids and calcinurin inhibitors used as first-line treatments, though both suffer from unwanted side effects. The topical PDE4 inhibitor crisaborole was approved for mild to moderate AD in 2020, but is…


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