PF-05221304 is a liver targeted inhibitor of acetyl-CoA carboxylase (ACC). ACC is a key regulator of lipid metabolism, and there has been significant interest in ACC inhibitors for the treatment of multiple indications including NASH and diabetes. Pfizer previously took a systemic ACC inhibitor into the clinic (PF-05175157), which was found [...]

On Mar. 14th, 2024, resmetirom (REZDIFFRA™) became the first and only medicine approved by the FDA for the treatment of NASH (non-alcoholic steatohepatitis, aka MASH). Resmetirom, an oral, liver-targeting, once-daily THR-β-selective agonist originally discovered at Roche Nutley, was first highlighted as a Molecule of the Month in Dec. 2022. Now, with the FDA’s accelerated approval, this 2023 Molecule of the Year nominee reflects a historic milestone for liver drug discovery. This article reviews how the molecule works, how it was discovered, and why it’s a big deal.

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 [...]

MK-1454 (Merck) is an intratumoral stimulator of interferon (IFN) genes (STING) agonist that is being developed for treatment of advanced solid tumors and lymphomas. The molecule follows Aduro’s ADU-S100 , which was terminated after Ph. II due to a lack of substantial activity. Another chemotype of STING agonist, Eisai’s E7766 , has [...]

Camlipixant is an orally administered antagonist of the ATP-sensing P2X3 homotrimeric receptor ion channel, originated by AstraZeneca AB and assigned to the Canadian NEOMED Institute (now adMare), and developed by BELLUS Health (Canada), for the treatment of chronic cough. Chronic cough remains difficult to treat – the last FDA-approved anti-tussive, dextromethorphan, was first approved in 1958 and has demonstrated limited clinical efficacy.