Evidence mapPaperPMID 41760780Full record

ArticleActa pharmacologica Sinica2026

A potential therapeutic effect of 84-B10 in MASLD through promotion of FASN degradation.

Yi-Peng Bai, Yin Yin, Su-Man Wang, Jiang-Ming Chen, Ze-Hua Zhang, Zi-Qi Zhu, Guang-Xin Shao, Yong Zhu, Yi-Yang Jiang, Bei-Cheng Sun and 1 more

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Article in Acta pharmacologica Sinica, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

11 authors.

Yi-Peng Bai *Department of Hepatobiliary Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China.
Yin Yin *Department of Hepatobiliary Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China.
Su-Man Wang *MOE Innovation Center for Basic Research in Tumor Immunotherapy, Hefei, 230032, China.
Jiang-Ming ChenDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China.
Ze-Hua ZhangDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China.
Zi-Qi ZhuMOE Innovation Center for Basic Research in Tumor Immunotherapy, Hefei, 230032, China.
Guang-Xin ShaoDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China.
Yong ZhuDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China.
Yi-Yang JiangDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China. yyjiang@ustc.edu.cn.
Bei-Cheng SunDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China. sunbc@ahmu.edu.cn.
Deng-Qiu XuDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China. xudengqiu@fy.ahmu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Recent evidence shows that fatty acid synthase (FASN), a key regulator of de novo lipogenesis (DNL), is a promising therapeutic target for metabolic dysfunction-associated steatotic liver disease (MASLD). FASN inhibitors are under advanced clinical trials. In this study, we evaluated the therapeutic efficacy of a novel FASN inhibitor 84-B10 for the treatment of MASLD. RNA-seq analysis showed that FASN was significantly upregulated in PA/OA-treated mouse primary hepatocytes. In silico molecular docking screening combined with biochemical assay, 84-B10 exhibited the strongest FASN-inhibiting effect. We demonstrated that 84-B10 directly bound to the MAT domain of FASN, inhibiting its enzymatic activity and promoting its ubiquitination and proteasomal degradation. In mouse primary hepatocytes, 84-B10 induced Lys48-linked ubiquitination of FASN by recruiting the E3 ligase tripartite motif-containing 28 (TRIM28), leading to FASN protein degradation. In PA/OA-treated mouse primary hepatocytes, 84-B10 (5, 10 μM) dose-dependently ameliorated lipid accumulation and mitochondrial dysfunction. In HFD-fed mice, administration of 84-B10 (5 mg/kg, i.g. every other day for 6 weeks) significantly alleviated metabolic alterations and hepatic lipid accumulation. Our results establish 84-B10 as a novel FASN inhibitor that activating the FASN-TRIM28 axis by binding to the MAT domain, facilitating the proteasomal degradation of FASN. With favorable safety, tolerability, and pharmacokinetic properties, 84-B10 holds promise as a therapeutic candidate for the prevention and treatment of MASLD.

Indexed as

Enzyme InhibitorsFatty Acid Synthase, Type INon-alcoholic Fatty Liver DiseaseAnimalsHepatocytesHumansMaleMiceMice, Inbred C57BLMolecular Docking SimulationProteolysisUbiquitinationEnzyme InhibitorsFasn protein, mouseFatty Acid Synthase, Type I84-B10FASN inhibitorlipid metabolismMASLDproteasomal degradationTRIM28

Identifiers

PMID41760780
PMCPMC13279807

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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 Socratic graph.