PF-07202954 / Pfizer - LARVOL DELTA

The translational potential of miR-26 in atherosclerosis and development of agents for its target genes ACC1/2, COL1A1, CPT1A, FBP1, DGAT2, and SMAD7. (PubMed, Cardiovasc Diabetol) - "Many agents targeting these genes, such as the ACC1/2 inhibitors GS-0976, PF-05221304, and MK-4074; the DGAT2 inhibitors IONIS-DGAT2Rx, PF-06427878, PF-0685571, and PF-07202954; the COL1A1 inhibitor HT-100; the stimulants Ga-CBP8 and RCT-01; the CPT1A inhibitors etomoxir, perhexiline, and teglicar; the FBP1 inhibitors CS-917 and MB07803; and the SMAD7 inhibitor mongersen, have been investigated in clinical trials...Many PCSK9 inhibitors, including alirocumab, evolocumab, inclisiran, AZD8233, Civi-007, MK-0616, and LIB003, have been investigated in clinical trials...Multiple materials can be used to deliver miR-26, but it is unclear which material is most suitable for mass production and clinical applications. This review focuses on the potential use of miR-26 in treating atherosclerosis to support the development of agents targeting it."

Journal • Review • Atherosclerosis • Cardiovascular • Dyslipidemia • Gastrointestinal Cancer • Hepatocellular Cancer • Oncology • Solid Tumor • ABCA1 • ACACA • ACSL3 • BMP2 • CD36 • COL1A1 • CPT1A • CTGF • EHHADH • HMGB1 • IFNA1 • IL1B • IL6 • MALT1 • RUNX2 • SCARB1 • SMAD7 • TCF7L2 • TNFA

Design of Next-Generation DGAT2 Inhibitor PF-07202954 with Longer Predicted Half-Life. (PubMed, ACS Med Chem Lett) - "This work culminated in the discovery of PF-07202954 (12), a weakly basic DGAT2 inhibitor that has advanced to clinical studies. This molecule displays a higher volume of distribution and longer half-life in preclinical species, in keeping with its physicochemical profile, and lowers liver triglyceride content in a Western-diet-fed rat model."

Journal • Hepatology • Non-alcoholic Steatohepatitis