Trial reportClinical pharmacology in drug development2020
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Liver-Targeting Acetyl-CoA Carboxylase Inhibitor (PF-05221304): A Three-Part Randomized Phase 1 Study.
Trial report in Clinical pharmacology in drug development, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 66 citations in OpenAlex.
- Exposure-response modeling of liver fat imaging endpoints in non-alcoholic fatty liver disease populations administered ervogastat alone and co-administered with clesacostat.CPT: pharmacometrics & systems pharmacology · 2025Trial
- SomaLogic proteomics reveals new biomarkers and provides mechanistic, clinical insights into Acetyl coA Carboxylase (ACC) inhibition in Non-alcoholic Steatohepatitis (NASH).Scientific reports · 2024Trial
- ACC inhibitor alone or co-administered with a DGAT2 inhibitor in patients with non-alcoholic fatty liver disease: two parallel, placebo-controlled, randomized phase 2a trials.Nature medicine · 2021Trial
- Inhibition of fatty acid synthase with FT-4101 safely reduces hepatic de novo lipogenesis and steatosis in obese subjects with non-alcoholic fatty liver disease: Results from two early-phase randomized trials.Diabetes, obesity & metabolism · 2021Trial
- Regulation of osteoclastogenesis and bone resorption by fatty acid metabolism: mechanisms and therapeutic opportunities.Frontiers in endocrinology · 2026Review
- Exploring the significance of fatty acid metabolism reprogramming in the pathogenesis of cancer and anticancer therapy.Annals of medicine · 2025Review
- Hidden in the Fat: Unpacking the Metabolic Tango Between Metabolic Dysfunction-Associated Steatotic Liver Disease and Metabolic Syndrome.International journal of molecular sciences · 2025Review
- Drug Pipeline for MASLD: What Can Be Learned from the Successful Story of Resmetirom.Current issues in molecular biology · 2025Review
- Highly Multiplexed Tissue Imaging in Precision Oncology and Translational Cancer Research.Cancer discovery · 2024Review
- Advances in management of metabolic dysfunction-associated steatotic liver disease: from mechanisms to therapeutics.Lipids in health and disease · 2024Review
- Investigation of pharmacokinetic drug interaction between clesacostat and DGAT2 inhibitor ervogastat in healthy adult participants.Clinical and translational science · 2024Article
- Pharmacologic inhibition of lipogenesis for the treatment of NAFLD.Journal of hepatology · 2024Review
- Isotope Labeling and Biochemical Assessment of Liver-Triacylglycerol in Patients with Different Levels of Histologically-Graded Liver Disease.The Journal of nutrition · 2023Article
- In-depth analysis ofLiver research (Beijing, China) · 2023Review
- Inflammation-induced TRIM21 represses hepatic steatosis by promoting the ubiquitination of lipogenic regulators.JCI insight · 2023Article
- Small molecule inhibitors for cancer metabolism: promising prospects to be explored.Journal of cancer research and clinical oncology · 2023Review
- Liver fibrosis and MAFLD: the exploration of multi-drug combination therapy strategies.Frontiers in medicine · 2023Review
- The Molecular Mechanisms of Liver Fibrosis and Its Potential Therapy in Application.International journal of molecular sciences · 2022Review
- Combinations of an acetyl CoA carboxylase inhibitor with hepatic lipid modulating agents do not augment antifibrotic efficacy in preclinical models of NASH and fibrosis.Hepatology communications · 2022Article
- Lipogenesis inhibitors: therapeutic opportunities and challenges.Nature reviews. Drug discovery · 2022Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
PF-05221304 is a liver-targeted inhibitor of acetyl-CoA carboxylase, an enzyme that catalyzes the first committed step in de novo lipogenesis (DNL). This first-in-human study investigated safety/tolerability and pharmacokinetics of single and multiple ascending oral PF-05221304 doses, and fructose-stimulated DNL inhibition with repeated oral doses. Healthy subjects (n = 96) received single (1-240 mg) or repeated (2-200 mg daily) doses for 14 days or single 100-mg doses with and without food. PF-05221304 was well tolerated at all doses. Repeated PF-05221304 doses inhibited hepatic DNL in a dose-dependent manner, with near-complete inhibition seen at higher doses. With doses yielding ≥90% DNL inhibition, asymptomatic increases in fasting/postprandial serum triglyceride levels (≥40 mg/day) and declines in platelet count (≥60 mg/day) occurred; these were not observed at ≤80% DNL inhibition. Steady-state pharmacokinetics generally increased dose-proportionally, with a half-life of 14-18 hours and a minimal food effect on plasma exposure. The observed safety and tolerability, pharmacokinetics, and pharmacodynamics support the continued evaluation of PF-05221304 for the treatment of nonalcoholic steatohepatitis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.