MK-4074 / Merck (MSD) - 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

Mechanism and therapeutic strategy of hepatic TM6SF2-deficient non-alcoholic fatty liver diseases via in vivo and in vitro experiments. (PubMed, World J Gastroenterol) - "TM6SF2 plays a protective role in the HFD condition; its deficiency enhanced hepatic lipid accumulation through dysregulated fatty acid metabolism, and MK-4074 treatment could alleviate the NAFLD phenotypes caused by TM6SF2 deficiency."

Journal • Preclinical • Hepatology • Metabolic Disorders • Non-alcoholic Fatty Liver Disease

Molecular Profiling Reveals a Common Metabolic Signature of Tissue Fibrosis. (PubMed, Cell Rep Med) - "We further show that pharmacological treatment of MK-8722 (AMPK activator) and MK-4074 (ACC inhibitor) reduce fibrosis in vivo. Altogether, our work demonstrate that metabolic defect is integral to TGF-β signaling and fibrosis."

Journal • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders

Partial inhibition of de novo lipogenesis with the acetyl-CoA carboxylase inhibitor PF-05221304 does not increase circulating triglycerides in humans and is sufficient to lower steatosis in rats (EASL-ILC 2019) - "Inhibition of ACC by MK-4074 was shown to inhibit DNL and reduce steatosis in patients with NAFLD along with unexpected increases in circulating triglyceride (TG) levels (Cell Metab. Doses of PF-05221304 which only partially inhibit hepatic DNL ( < 80% inhibition) did not elevate fasting or 24 hour serum TG levels in adult humans. Partial inhibition of hepatic DNL (58% and 73%) was sufficient to robustly lower steatosis in Western-diet-fed rats. Additional studies are needed to determine if these findings translate to patients with NASH."

Preclinical