Molecular Pharmacology最新文献

{"title":"Corrigendum to \"A subunit-selective negative allosteric modulator of GluN1/GluN3A glycine-activated receptor\" [Molecular Pharmacology 108 (2026) 100104].","authors":"Leon Jacobs, TrangKimberly T Nguyen, Adam McCallum, Matt P Epplin, Riley E Perszyk, Scott J Myers, Ken Liu, Yanli Yang, Aletta E Van der Westhuyzen, Kelsey A Nocilla, James Allen, Elijah Z Ullman, Ding Liu, Yufei Du, Hongjie Yuan, Dennis C Liotta, Stephen F Traynelis","doi":"10.1016/j.molpha.2026.100118","DOIUrl":"10.1016/j.molpha.2026.100118","url":null,"abstract":"","PeriodicalId":18767,"journal":{"name":"Molecular Pharmacology","volume":"108 4","pages":"100118"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147593224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Differential impacts of exon 1-associated and exon 11-associated variants of the rat mu opioid receptor gene, Oprm1, on buprenorphine- and morphine-induced analgesia and respiratory depression in male rats.","authors":"Tiffany Zhang, Jin Xu, Valerie P Le Rouzic, Yudelca Ogando, Ayma F Malik, Raymond Chien, Miyasaka Yoshiki, Tomoji Mashimo, Thomas L Saunders, Channabasavaiah B Gurumurthy, Ying-Xian Pan","doi":"10.1016/j.molpha.2026.100112","DOIUrl":"10.1016/j.molpha.2026.100112","url":null,"abstract":"<p><p>Buprenorphine has long been recognized as a mu opioid agonist with a distinctive and intricate pharmacological profile. It is a partial agonist at the mu opioid receptor, an antagonist at the kappa and delta opioid receptors, and an agonist at the nociception opioid receptor. Similar to other mu agonists such as morphine and fentanyl, buprenorphine can produce side effects, including tolerance, physical dependence, respiratory depression, and addiction. The mu opioid receptor gene, OPRM1, undergoes extensive alternative splicing, generating an array of splice variants or isoforms, which are conserved from rodents to humans. These splice variants can be categorized into 2 main types, exon 1 (E1)-associated variants and exon 11 (E11)-associated variants. E1-associated variants primarily consist of full-length, 7-transmembrane C-terminal variants, whereas E11-associated variants are typically truncated 6-transmembrane variants. Previous studies established that buprenorphine analgesia in mice is dependent on both E1- and E11-associated variants. However, the role of these variants in buprenorphine analgesia and respiratory depression in rats remains unclear. In this study, we used CRISPR/Cas9 technology to develop 2 rat Oprm1 gene-targeting models in which E1- and E11-associated variants were selectively disrupted, aiming to investigate their roles in buprenorphine and morphine's actions. The results showed that both E1- and E11-associated variants are essential for buprenorphine's analgesic and respiratory depressional effects in rats, whereas morphine's effects are solely attributed to the E1-associated variants. These findings provide new and important insights into the distinct contributions of the E1- and E11-associated variants to the pharmacological actions of buprenorphine and morphine. SIGNIFICANCE STATEMENT: Differential dependences of buprenorphine and morphine analgesia and respiratory depression on Oprm1 exon 1- and exon 11-associated variants revealed in rat gene-targeting models provide new and important insights into unique contributions of these variants to buprenorphine and morphine actions.</p>","PeriodicalId":18767,"journal":{"name":"Molecular Pharmacology","volume":"108 4","pages":"100112"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13197947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147372875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expressions of Concern, Corrigenda, and a Retraction.","authors":"Beverley Greenwood-Van Meerveld, John J G Tesmer, Michael Jarvis","doi":"10.1016/j.molpha.2026.100106","DOIUrl":"10.1016/j.molpha.2026.100106","url":null,"abstract":"","PeriodicalId":18767,"journal":{"name":"Molecular Pharmacology","volume":" ","pages":"100106"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147618718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Elucidating the binding and metabolic interactions of sunitinib and sorafenib with Cytochrome P450s CYP2U1 and CYP2D6.","authors":"Tiffany Y-C Tang, Yupeng Li, Peter Chapman, Emad Tajkhorshid, Aditi Das","doi":"10.1016/j.molpha.2026.100114","DOIUrl":"10.1016/j.molpha.2026.100114","url":null,"abstract":"<p><p>Cytochrome P450 2U1 (CYP2U1) is an extrahepatic monooxygenase that metabolizes both endogenous fatty acids and xenobiotic substrates. Because of its high expression in both healthy and cancerous thymus tissues, this study investigated CYP2U1-mediated biotransformation of 2 tumor-targeting tyrosine kinase inhibitors, sorafenib and sunitinib, both are commonly prescribed for thymus cancers. Recombinantly expressed CYP2U1 and CYP2D6 were incorporated into nanodiscs, and their metabolism of sorafenib and sunitinib was investigated. Liquid chromatography-tandem mass spectrometry metabolite profiling revealed that both CYP2U1 and CYP2D6 nanodiscs oxidized sorafenib to generate sorafenib N-oxide and both enzymes catalyzed the dealkylation of sunitinib to form N-desethyl sunitinib. Spectroscopic studies (UV-Visible and fluorescence) confirmed favorable binding interactions of CYP2U1 and CYP2D6 to both drugs tested. Molecular dynamics simulations demonstrated binding of sorafenib and sunitinib in the CYP2U1 active site and identified key interactions between the drug and key residues at the enzyme's active site. Rates of metabolite formation were quantified by targeted metabolomics, and inhibition of tyrosine kinase was assessed by ELISA assay. Both the parent compound sorafenib and metabolite sorafenib N-oxide showed similar inhibitory effects on cellular migration in HepG2 cells. The metabolite sorafenib N-oxide was approximately twice as potent as the parent compound in inhibiting cancer cell migration. In contrast, N-desethyl sunitinib failed to show similar extent of inhibition. Together, these findings highlight the potential role of extrahepatic CYP2U1 in the local metabolism of tyrosine kinase inhibitors and suggest that CYP2U1-mediated transformations directly influence antitumor efficacy at thymic tumor sites. SIGNIFICANCE STATEMENT: Understanding the interactions between cytochrome P450 2U1 and cytochrome P450 2D6 in nanodiscs and thymus tumor-targeting drugs, sorafenib and sunitinib, led to discovery of new bioactive metabolites that carry differential anticancer properties compared with their parent compounds.</p>","PeriodicalId":18767,"journal":{"name":"Molecular Pharmacology","volume":"108 4","pages":"100114"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13169326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147633937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanobodies unlock new mechanisms to target G protein-coupled receptors.","authors":"Meredith A Skiba","doi":"10.1016/j.molpha.2026.100110","DOIUrl":"10.1016/j.molpha.2026.100110","url":null,"abstract":"<p><p>Once considered tools to aid structural studies, single-domain antibodies (nanobodies) have emerged as a new class of G protein-coupled receptor (GPCR) ligands. Aided by camelid immunization and advances in synthetic nanobody library development and computational design platforms, nanobody discovery has expanded to all major GPCR families. Unlike traditional small-molecule ligands, nanobodies can engage extended nonconserved extracellular epitopes to stabilize distinct receptor conformations to achieve high receptor selectivity and enable unique modes of pharmacological modulation. Integration of these properties with classical antibody engineering approaches, such as the generation of bispecific or bivalent constructs, has the potential to enable additional therapeutic strategies, such as cell and tissue-specific targeting. Recent mechanistic studies provide insight into the strategies nanobodies employ to function as agonists, antagonists, inverse agonists, and allosteric modulators. These studies begin to reveal the general principles nanobodies use to selectively engage and regulate GPCRs and uncover strategies to evolve their pharmacological properties. Continued advancements in discovery methods will expand the repertoire of nanobody ligands across additional GPCRs and deepen our mechanistic understanding to accelerate the development of the next generation of GPCR therapeutics. SIGNIFICANCE STATEMENT: G protein-coupled receptors (GPCRs) are one of the most successful targets of small-molecule drugs but are virtually untouched by antibody therapeutics. Aided by advances in discovery strategies, nanobodies have emerged as an ideal antibody scaffold to modulate GPCR signaling. Recent mechanistic studies reveal the molecular approaches nanobodies employ to target GPCRs, providing new insight into their potential as therapeutic tools. These findings provide a path toward developing nanobodies to regulate GPCR function in diverse disease contexts.</p>","PeriodicalId":18767,"journal":{"name":"Molecular Pharmacology","volume":"108 4","pages":"100110"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13169046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147372889","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of potential autophagy inducers through high-throughput and high-content imaging analysis.","authors":"Masato Ooka, Leah Mitchell, Jinghua Zhao, Zhengxi Wei, Li Zhang, Danielle Bougie, Hsiu-Ling Lin, Yuhong Fang, Dingyin Tao, Kelli Wilson, Wen-Xing Ding, Ruili Huang, Menghang Xia","doi":"10.1016/j.molpha.2026.100116","DOIUrl":"10.1016/j.molpha.2026.100116","url":null,"abstract":"<p><p>Autophagy is a cellular degradation process that plays a critical role in maintaining homeostasis and preventing stress-induced damage, making it a promising therapeutic target for cancer and neurodegenerative diseases. In this study, we utilized mouse embryonic fibroblasts expressing GFP-labeled microtubule-associated protein 1 light chain 3, a widely used biomarker of autophagy activation, to screen 3733 clinically approved or investigational drugs using a high-throughput and high-content screening platform. From the primary screening, 117 compounds were identified as potential autophagy inducers. Subsequent confirmation studies narrowed this group to 5 previously uncharacterized autophagy-inducing candidates for further investigation. Follow-up studies assessed the mechanisms underlying autophagy modulation by these compounds, with a focus on key pathways such as mechanistic target of rapamycin inhibition, endoplasmic reticulum stress activation, and p53 activation. To further explore their therapeutic potential in cancer, we conducted an angiogenesis inhibition assay. This study successfully identified several autophagy inducers that may be repurposed for the treatment of cancer, highlighting their potential for future therapeutic development. SIGNIFICANT STATEMENT: This study identifies novel autophagy inducers from high-throughput screening of approved and investigational drugs. The findings highlight key pathways such as mechanistic target of rapamycin inhibition and endoplasmic reticulum stress activation, and demonstrate the ability of these compounds to inhibit angiogenesis, suggesting their potential for repurposing in cancer therapy.</p>","PeriodicalId":18767,"journal":{"name":"Molecular Pharmacology","volume":"108 4","pages":"100116"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13168962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147574491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CXCR1 and CXCR2 display receptor bias for shared chemokine agonists.","authors":"Chanpreet Jassal, Joseph Strawn, Emily Walsh, Krishna Rajarathnam, Sudarshan Rajagopal","doi":"10.1016/j.molpha.2026.100117","DOIUrl":"10.1016/j.molpha.2026.100117","url":null,"abstract":"<p><p>G protein-coupled receptors (GPCRs) mediate diverse signaling outputs through their proximal transducers: G proteins, GPCR kinases, and β-arrestins. Although ligand bias at chemokine receptors (CKRs), where ligands for the same receptor display distinct signaling patterns, is well recognized, receptor bias, where the same agonist at different receptors yields distinct transducer engagement, remains poorly understood. We compared endogenous chemokine ligands (CXCL1, CXCL5, CXCL7, CXCL8) at the highly homologous CXCR1 and CXCR2 using biosensor assays to measure Gαi activation, β-arrestin1/2 recruitment, GPCR kinase 2/3/5/6 translocation, and receptor internalization. Our data reveal qualitatively different signaling patterns, most notably where CXCL1 acts as a G protein-biased partial agonist at CXCR1 but as a balanced full agonist at CXCR2. These signaling differences correlate with receptor internalization but not subcellular ERK activation patterns measured using compartment-specific biosensors. Collectively, our findings demonstrate receptor bias in CKR signaling, transducer activation, and compartmentalized kinase activation in translating chemokine identity into discrete functional outcomes. SIGNIFICANCE STATEMENT: Ligand bias, where different ligands for the same receptor display different signaling patterns, is now well appreciated. However, there are only a few examples of receptor bias, where the same agonist generates distinct signaling profiles at different receptors. This study used biosensors and compartmental ERK biosensors to show that shared ligands of CXCR1 and CXCR2 differentially engage G proteins, β-arrestins, and G protein-coupled receptor kinases, revealing receptor bias in CXCL1-mediated signaling that extends beyond prior characterizations.</p>","PeriodicalId":18767,"journal":{"name":"Molecular Pharmacology","volume":"108 4","pages":"100117"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13168994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147574562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rare variant in intracellular loop-2 alters the spatial distribution and transducer coupling selectivity of the ghrelin receptor.","authors":"Elsa M Balfe, Alexandre Torbey, Tomasz M Stepniewski, Yang Zhou, Lara Kohlenbach, Jade A Sency, Asuka Inoue, Lauren M Slosky, Jana Selent, Lawrence S Barak, Joshua D Gross","doi":"10.1016/j.molpha.2026.100119","DOIUrl":"10.1016/j.molpha.2026.100119","url":null,"abstract":"<p><p>G protein-coupled receptors (GPCRs) are the largest class of membrane proteins and the most common pharmaceutical drug target. Prior work from our group and others supports that a conserved, proline-hydrophobic residue (ProH) motif within intracellular loop-2 (ICL2) biases GPCR-transducer coupling between canonical G proteins and β-arrestin (βarr). Here, we systematically characterize a rare missense mutation within the ProH motif of the ghrelin receptor (growth hormone secretagogue receptor [GHSR])-Leu149Pro^34.51 (L149P)-to dissect how naturalistic perturbation of ICL2 dynamics pleiotropically regulates the spatial distribution, trafficking, and transducer selectivity of a prototypical, rhodopsin-like GPCR. Molecular dynamics simulations indicate that the L149P mutation destabilizes the α-helical conformation of ICL2, thereby increasing loop flexibility proximal to the receptor-transducer coupling interface. Using a panel of bioluminescence resonance-energy transfer biosensors combined with pharmacological and genetic tools, we demonstrate that the GHSR-L149P mutation (1) enhances receptor surface expression by reducing constitutive GHSR trafficking; (2) biases transducer engagement toward βarr1/2 and Gα_i/o over Gα_q and Gα₁₃, despite partial mini-G_q coupling efficacy; (3) expands GPCR kinase (GRK) subclass utilization from GRK2/3-dependent to an additional, partial reliance on GRK5/6; and (4) promotes βarr1/2 recruitment independent of G protein-mediated second messenger kinase activation. The evolutionary conservation of the ProH motif suggests that cognate, ICL2-destabilizing variants likely confer comparable disruptions in GPCR structure/function beyond established effects on G protein coupling. Collectively, these results establish a naturalistic model to study ICL2-dependent GPCR regulation and illuminate the ProH motif as a promising drug target for biased allosteric modulators. SIGNIFICANCE STATEMENT: G protein-coupled receptors are the most common pharmaceutical target in medicine. This study exploited a rare variant in intracellular loop-2 of the ghrelin receptor to characterize a conserved, allosteric \"hotspot\" controlling G protein-coupled receptor expression, trafficking, and signaling. These findings highlight intracellular loop-2 as a promising target for biased allosteric modulator drug design.</p>","PeriodicalId":18767,"journal":{"name":"Molecular Pharmacology","volume":"108 4","pages":"100119"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pseudokinases in neurodevelopment and disease.","authors":"Moira Cornell, Smita Yadav","doi":"10.1016/j.molpha.2026.100113","DOIUrl":"10.1016/j.molpha.2026.100113","url":null,"abstract":"<p><p>Pseudokinases are enigmatic proteins that evolved such that they retained the evolutionarily conserved kinase-like fold but lost key residues required for substrate phosphorylation. Pseudokinases have unique functions ranging from altered enzymatic ability, modulation of other protein kinases, and acting as scaffolds or substrate sponges. Nowhere perhaps is this functional diversity more evident than the seemingly myriad roles of pseudokinases in brain development. Not surprisingly, mutations in pseudokinases are associated with several clinically significant neurodevelopmental disorders. Here, we review 5 such pseudokinases, their known functional roles in brain development, disease association, and the unanswered questions that remain. Addressing the unexplored landscape of pseudokinases in neurological disorders holds promise of uncovering important insights into neuropathology and novel therapeutic targets. SIGNIFICANCE STATEMENT: Pseudokinases are understudied proteins that lack the catalytic ability to mediate phosphorylation, yet, they perform extraordinary and physiologically essential signaling functions. This review highlights the importance of pseudokinases in brain development and how their dysregulation leads to neurological disorders. Greater understanding of the structure, function, and regulation of pseudokinases is critical for the design of small molecules that can modulate their function.</p>","PeriodicalId":18767,"journal":{"name":"Molecular Pharmacology","volume":"108 4","pages":"100113"},"PeriodicalIF":3.0,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147530631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cepharanthine, a valuable sanative alternative for hepatocellular carcinoma through regulating Hippo-Yes-associated protein signal transduction.","authors":"Kejun Hu, Yukai Zhao, Xinyu Fu, Sai Li, Ting Wu, Wangwang Liu, Wei Wang, Cheng Cheng, Huanhuan Qiu, Shumin Pan, Qi Lv, Guanglin Xu","doi":"10.1016/j.molpha.2026.100105","DOIUrl":"10.1016/j.molpha.2026.100105","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) stands as a prevalent form of primary liver cancer, distinguished by challenging diagnosis and grim prognoses. Its global mortality rate is on the rise, compounded by the insensitivity of patients with HCC to conventional anticancer medications. The dysregulation of the Hippo-Yes-associated protein (YAP) signaling pathway closely intertwines with HCC progression, notably marked by a significant elevation in YAP expression within hepatocellular carcinoma. Cepharanthine, derived primarily from the Stephania cepharantha Hayata plant, emerges as a natural compound renowned for its diverse anticancer properties, capable of impeding the proliferation across various cancer cell lines. However, the precise mechanism by which cepharanthine influences HCC cells and its impact on the Hippo-YAP signaling pathway remains elusive. In this investigation, we used 2 distinct HCC cell lines alongside nude mice with xenograft tumors to scrutinize the antitumor potential of cepharanthine. Our findings reveal that cepharanthine effectively curbs the proliferation of hepatocellular carcinoma cells, retarding tumor growth. Moreover, it diminishes YAP expression within HCC cells and tumors, instigates YAP phosphorylation, and sequesters YAP within the cytoplasm. Consequently, the transcription and expression of YAP downstream target genes experience a notable decrease. Furthermore, we explored the influence of YAP expression levels on the pharmacodynamics of cepharanthine, leveraging YAP overexpression or knockdown techniques. This experimental strategy confirmed that cepharanthine exerts its antihepatoma efficacy by intervening in the Hippo-YAP signaling pathway. SIGNIFICANCE STATEMENT: This study highlights the potential of cepharanthine as a novel therapeutic agent for hepatocellular carcinoma by demonstrating its ability to inhibit tumor growth through the regulation of the Hippo-Yes-associated protein signaling pathway. Key findings include cepharanthine's capacity to reduce Yes-associated protein expression, promote its phosphorylation, and prevent nuclear translocation, thereby suppressing downstream proliferation-related genes. These insights offer a promising direction for developing effective treatments against hepatocellular carcinoma, addressing the urgent need for new therapeutic strategies in oncology.</p>","PeriodicalId":18767,"journal":{"name":"Molecular Pharmacology","volume":"108 3","pages":"100105"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147307840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}