Resmetirom is an oral, liver-targeting, once-daily THRβ-selective agonist, which in December 2022 became the first drug to meet its primary endpoints in Ph. III for NASH, demonstrating both NASH resolution and no worsening of fibrosis by biopsy over placebo in 316 test patients. Madrigal will file an NDA for resmetirom in 2023, allowing it to [...]

DS-3801b is a non-macrolide GPR38 agonist and a Ph. I clinical candidate for treatment of chronic constipation (SAD 1-100 mg PO). GPR38 is the receptor for the GI hormone motilin, which as the name suggests, regulates GI motility. Agonism of GPR38 is expected to reduce constipation by activating GI tract smooth muscle cells to move things [...]

The Mirum Pharmaceuticals IBAT bile acid transporter inhibitor, maralixibat , has a long history, having been first patented by scientists at Searle in 1994 and published by the time Searle became part of Pharmacia in 2005 . It was finally approved in Sep. 2021 for treatment of cholestatic pruritis in patients with Alagille Syndrome, and is [...]

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 [...]

The Janssen gut-restricted COX-2 inhibitor, compound 10 , is a tool compound used to test the hypothesis that gut-restricted COX-2 inhibition would be beneficial for cancer without the cardiovascular risk of systemic COX-2 inhibition. Unfortunately, IVIVC of several compounds demonstrated that in vivo efficacy was not driven by gut COX-2 [...]