Molecular Pharmacology最新文献

{"title":"The evolution of patch-clamp electrophysiology: robotic, multiplex, and dynamic.","authors":"Mohammad-Reza Ghovanloo, Sulayman D Dib-Hajj, Stephen G Waxman","doi":"10.1124/molpharm.124.000954","DOIUrl":"https://doi.org/10.1124/molpharm.124.000954","url":null,"abstract":"<p><p>The patch-clamp technique has been the gold standard for analysis of excitable cells. Since its development in the 1980s it has contributed immensely to our understanding of neurons, muscle cells, and cardiomyocytes, and the ion channels and receptors that reside within them. This technique, predicated on Ohm's law, enables precise measurements of macroscopic excitability patterns, and ionic and gating conductances that can be assessed even down to the single channel level. Over the years, patch-clamp electrophysiology has undergone extensive modifications, with the introduction of new applications that have enhanced its power and reach. The most recent evolution of this technique occurred with the introduction of robotic high throughput automated platforms that enable high quality simultaneous recordings, in both voltage- and current-clamp modes, from 10s to 100s of cells, including cells freshly isolated from their native tissues. Combined with new dynamic-clamp applications, these new methods provide increasingly powerful tools for studying the contributions of ion channels and receptors to electrogenesis. In this brief review, we provide an overview of these enhanced patch-clamp techniques, followed by some of the applications presently being pursued, and a perspective into the potential future of the patch-clamp method. <b>Significance Statement</b> The patch-clamp technique, introduced in the 1980s, has revolutionized understanding of electrogenesis. Predicated on Ohm's law, this approach facilitates exploration of ionic conductances, gating mechanisms of ion channels and receptors, and their roles in neuronal, muscular, and cardiac excitability. Robotic platforms for high-throughput patch-clamp, and dynamic-clamp, have recently expanded its reach. Here, we outline new advances in patch-clamp including high throughput analysis of freshly-isolated neurons, and discuss the increasingly powerful trajectory of new patch-clamp techniques.</p>","PeriodicalId":18767,"journal":{"name":"Molecular Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142009043","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":"Participation of Ca²⁺-Calmodulin-Dependent Protein Kinase II in the Antidepressant-Like Effects of Melatonin.","authors":"Armida Miranda-Riestra, Montserrat G Cercós, Citlali Trueta, Julián Oikawa-Sala, Jesús Argueta, Luis A Constantino-Jonapa, Ricardo Cruz-Garduño, Gloria Benítez-King, Rosa Estrada-Reyes","doi":"10.1124/molpharm.124.000890","DOIUrl":"10.1124/molpharm.124.000890","url":null,"abstract":"<p><p>Melatonin (<i>N</i>-acetyl-5-methoxytryptamine) is an indoleamine secreted by the pineal gland during the dark phase of the photoperiod. Its main function is the synchronization of different body rhythms with the dark-light cycle. Research on melatonin has significantly advanced since its discovery and we now know that it has considerable significance in various physiological processes, including immunity, aging, and reproduction. Moreover, in recent years evidence of the pharmacological possibilities of melatonin has increased. Indoleamine, on the other hand, has antidepressant-like effects in rodents, which may be mediated by the activation of calcium-calmodulin-dependent kinase II (CaMKII) and are also related to the regulation of neuroplasticity processes, including neurogenesis, synaptic maintenance, and long-term potentiation. Remarkably, patients with major depression show decreased levels of circulating melatonin in plasma. This review presents evidence of the antidepressant-like effects of melatonin in preclinical models and the participation of CaMKII in these actions. CaMKII's role in cognition and memory processes, which are altered in depressive states, are part of the review, and the effects of melatonin in these processes are also reviewed. Furthermore, participation of CaMKII on structural and synaptic plasticity and the effects of melatonin are also described. Finally, the advantages of using melatonin in combination with other antidepressants such as ketamine for neuroplasticity are described. Evidence supports that CaMKII is activated by melatonin and downstream melatonin receptors and may be the common effector in the synergistic effects of melatonin with other antidepressants. SIGNIFICANCE STATEMENT: This review compiled evidence supporting that melatonin causes antidepressant-like effects in mice through calmodulin kinase II stimulation of downstream melatonin receptors as well as the participation of this enzyme in neuroplasticity, memory, and cognition. Finally, we describe evidence about the effectiveness of antidepressant-like effects of melatonin in combination with ketamine.</p>","PeriodicalId":18767,"journal":{"name":"Molecular Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141856022","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":"Aulosirazole Stimulates FOXO3a Nuclear Translocation to Regulate Apoptosis and Cell-Cycle Progression in High-Grade Serous Ovarian Cancer (HGSOC) Cells.","authors":"Manead Khin, Lydia J Davis, Daniel D Lantvit, Jimmy Orjala, Joanna E Burdette","doi":"10.1124/molpharm.124.000921","DOIUrl":"10.1124/molpharm.124.000921","url":null,"abstract":"<p><p>Ovarian cancer, the fifth leading cause of cancer-related mortality in women, is the most lethal gynecological malignancy globally. Within various ovarian cancer subtypes, high-grade serous ovarian cancer is the most prevalent and there is frequent emergence of chemoresistance. Aulosirazole, an isothiazolonaphthoquinone alkaloid, isolated from the cyanobacterium <i>Nostoc</i> sp. UIC 10771, demonstrated cytotoxic activity against OVCAR3 cells (IC₅₀ = 301 ± 80 nM). Using immunocytochemistry, OVCAR3 cells treated with aulosirazole demonstrated increased concentrations of phosphorylated protein kinase B and phosphorylated c-Jun N-terminal kinase with subsequent accumulation of forkhead box O3a (FOXO3a) in the nucleus. The combination of aulosirazole with protein kinase B inhibitors resulted in the most nuclear accumulation of FOXO3a aulosirazole-induced apoptosis based on cleavage of poly(ADP-ribose) polymerase, annexin V staining, and induction of caspase 3/7 activity in OVCAR3, OVCAR5, and OVCAR8. The expression of downstream targets of FOXO3a, including B-cell lymphoma 2 (BCL2) and p53-upregulator modulator of apoptosis, increased following aulosirazole treatment. Aulosirazole upregulated the FOXO3a target, cyclin-dependent kinase inhibitor 1, and increased cell-cycle arrest in the G0/G1 phase. The downregulation of FOXO3a by short hairpin RNA (shRNA) reduced the cytotoxicity after aulosirazole treatment by 3-fold IC₅₀ (949 ± 16 nM) and eliminated its ability to regulate downstream targets of FOXO3a. These findings underscore FOXO3a as a critical mediator of aulosirazole-induced cytotoxicity. Additionally, aulosirazole was able to decrease migration and invasion while increasing cell death in 3D tumor spheroids. However, in vivo OVCAR8 tumor burden was not reduced by aulosirazole using an intraperitoneal tumor model. Given the mechanism of action of aulosirazole, this class of alkaloids represents promising lead compounds to develop treatments against FOXO3a-downregulated cancers. SIGNIFICANCE STATEMENT: Aulosirazole, an isothiazolonaphthoquinone alkaloid, exhibits potent cytotoxic effects against high-grade serous ovarian cancer by promoting forkhead box O3a (FOXO3a) nuclear accumulation and modulating downstream targets. These findings highlight the potential of aulosirazole as a promising therapeutic intervention for cancers characterized by FOXO3a downregulation.</p>","PeriodicalId":18767,"journal":{"name":"Molecular Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11331498/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141856021","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":"New Mechanisms Underlying Oncogenesis in Dbl Family Rho Guanine Nucleotide Exchange Factors.","authors":"Sandeep K Ravala, John J G Tesmer","doi":"10.1124/molpharm.124.000904","DOIUrl":"10.1124/molpharm.124.000904","url":null,"abstract":"<p><p>Transmembrane signaling is a critical process by which changes in the extracellular environment are relayed to intracellular systems that induce changes in homeostasis. One family of intracellular systems are the guanine nucleotide exchange factors (GEFs), which catalyze the exchange of GTP for GDP bound to inactive guanine nucleotide binding proteins (G proteins). The resulting active G proteins then interact with downstream targets that control cell proliferation, growth, shape, migration, adhesion, and transcription. Dysregulation of any of these processes is a hallmark of cancer. The Dbl family of GEFs activates Rho family G proteins, which, in turn, alter the actin cytoskeleton and promote gene transcription. Although they have a common catalytic mechanism exercised by their highly conserved Dbl homology (DH) domains, Dbl GEFs are regulated in diverse ways, often involving the release of autoinhibition imposed by accessory domains. Among these domains, the pleckstrin homology (PH) domain is the most commonly observed and found immediately C-terminal to the DH domain. The domain has been associated with both positive and negative regulation. Recently, some atomic structures of Dbl GEFs have been determined that reemphasize the complex and central role that the PH domain can play in orchestrating regulation of the DH domain. Here, we discuss these newer structures, put them into context by cataloging the various ways that PH domains are known to contribute to signaling across the Dbl family, and discuss how the PH domain might be exploited to achieve selective inhibition of Dbl family RhoGEFs by small-molecule therapeutics. SIGNIFICANCE STATEMENT: Dysregulation via overexpression or mutation of Dbl family Rho guanine nucleotide exchange factors (GEFs) contributes to cancer and neurodegeneration. Targeting the Dbl homology catalytic domain by small-molecule therapeutics has been challenging due to its high conservation and the lack of a discrete binding pocket. By evaluating some new autoinhibitory mechanisms in the Dbl family, we demonstrate the great diversity of roles played by the regulatory domains, in particular the PH domain, and how this holds tremendous potential for the development of selective therapeutics that modulate GEF activity.</p>","PeriodicalId":18767,"journal":{"name":"Molecular Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11331503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432329","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":"Get Ready to Sharpen Your Tools: A Short Guide to Heterotrimeric G Protein Activity Biosensors.","authors":"Remi Janicot, Mikel Garcia-Marcos","doi":"10.1124/molpharm.124.000949","DOIUrl":"10.1124/molpharm.124.000949","url":null,"abstract":"<p><p>G protein-coupled receptors (GPCRs) are the largest class of transmembrane receptors encoded in the human genome, and they initiate cellular responses triggered by a plethora of extracellular stimuli ranging from neurotransmitters and hormones to photons. Upon stimulation, GPCRs activate heterotrimeric G proteins (G<i>αβ</i>γ) in the cytoplasm, which then convey signals to their effectors to elicit cellular responses. Given the broad biological and biomedical relevance of GPCRs and G proteins in physiology and disease, there is great interest in developing and optimizing approaches to measure their signaling activity with high accuracy and across experimental systems pertinent to their functions in cellular communication. This review provides a historical perspective on approaches to measure GPCR-G protein signaling, from quantification of second messengers and other indirect readouts of activity to biosensors that directly detect the activity of G proteins. The latter is the focus of a more detailed overview of the evolution of design principles for various optical biosensors of G protein activity with different experimental capabilities. We will highlight advantages and limitations of biosensors that detect different G protein activation hallmarks, like dissociation of G<i>α</i> and G<i>β</i>γ or nucleotide exchange on G<i>α</i>, as well as their suitability to detect signaling mediated by endogenous versus exogenous signaling components or in physiologically relevant systems like primary cells. Overall, this review intends to provide an assessment of the state-of-the-art for biosensors that directly measure G protein activity to allow readers to make informed decisions on the selection and implementation of currently available tools. SIGNIFICANCE STATEMENT: G protein activity biosensors have become essential and widespread tools to assess GPCR signaling and pharmacology. Yet, investigators face the challenge of choosing from a growing list of G protein activity biosensors. This review provides an overview of the features and capabilities of different optical biosensor designs for the direct detection of G protein activity in cells, with the aim of facilitating the rational selection of systems that align with the specific scientific questions and needs of investigators.</p>","PeriodicalId":18767,"journal":{"name":"Molecular Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11331509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141590781","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":"<i>N</i>-(4-Bromo-2,5-Dimethoxyphenethyl)-6-(4-Phenylbutoxy)Hexan-1-Amine (XOB): A Novel Phenylalkylamine Antagonist of Serotonin 2A Receptors and Voltage-Gated Sodium Channels.","authors":"Nicholas Denomme, Ciria C Hernandez, Hailey A Bock, Rachel F Ohana, Shreeya Bakshi, Alexander M Sherwood, John D McCorvy, Paul F Daley, Wyeth B Callaway, Jacob M Hull, Andrew Alt, Lori L Isom, Nicholas V Cozzi","doi":"10.1124/molpharm.123.000837","DOIUrl":"10.1124/molpharm.123.000837","url":null,"abstract":"<p><p>Bipolar disorder impacts millions of patients in the United States but the mechanistic understanding of its pathophysiology and therapeutics is incomplete. Atypical antipsychotic serotonin_2A (5-HT_2A) receptor antagonists, such as quetiapine and olanzapine, and mood-stabilizing voltage-gated sodium channel (VGSC) blockers, such as lamotrigine, carbamazepine, and valproate, show therapeutic synergy and are often prescribed in combination for the treatment of bipolar disorder. Combination therapy is a complex task for clinicians and patients, often resulting in unexpected difficulties with dosing, drug tolerances, and decreased patient compliance. Thus, an unmet need for bipolar disorder treatment is to develop a therapeutic agent that targets both 5-HT_2A receptors and VGSCs. Toward this goal, we developed a novel small molecule that simultaneously antagonizes 5-HT_2A receptors and blocks sodium current. The new compound, <i>N</i>-(4-bromo-2,5-dimethoxyphenethyl)-6-(4-phenylbutoxy)hexan-1-amine (XOB) antagonizes 5-HT-stimulated, G_q-mediated, calcium flux at 5-HT_2A receptors at low micromolar concentrations while displaying negligible affinity and activity at 5-HT_1A, 5-HT_2B, and 5-HT_2C receptors. At similar concentrations, XOB administration inhibits sodium current in heterologous cells and results in reduced action potential (AP) firing and VGSC-related AP properties in mouse prefrontal cortex layer V pyramidal neurons. Thus, XOB represents a new, proof-of-principle tool that can be used for future preclinical investigations and therapeutic development. This polypharmacology approach of developing a single molecule to act upon two targets, which are currently independently targeted by combination therapies, may lead to safer alternatives for the treatment of psychiatric disorders that are increasingly being found to benefit from the simultaneous targeting of multiple receptors. SIGNIFICANCE STATEMENT: The authors synthesized a novel small molecule (XOB) that simultaneously antagonizes two key therapeutic targets of bipolar disorder, 5-HT_2A receptors and voltage-gated sodium channels, in heterologous cells, and inhibits the intrinsic excitability of mouse prefrontal cortex layer V pyramidal neurons in brain slices. XOB represents a valuable new proof-of-principle tool for future preclinical investigations and provides a novel molecular approach to the pharmacological treatment of complex neuropsychiatric disease, which often requires a combination of therapeutics for sufficient patient benefit.</p>","PeriodicalId":18767,"journal":{"name":"Molecular Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11254453/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141184187","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":"Correction to \"A Brief Overview of the Toxic Sphingomyelinase Ds of Brown Recluse Spider Venom and Other Organisms and Simple Methods To Detect Production of Its Signature Cyclic Ceramide Phosphate\".","authors":"","doi":"10.1124/molpharm.123.000709err","DOIUrl":"https://doi.org/10.1124/molpharm.123.000709err","url":null,"abstract":"","PeriodicalId":18767,"journal":{"name":"Molecular Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419889","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":"Allosteric Inhibition and Pharmacochaperoning of the Serotonin Transporter by the Antidepressant Drugs Trazodone and Nefazodone.","authors":"Ali El-Kasaby, Danila Boytsov, Ameya Kasture, Günther Krumpl, Thomas Hummel, Michael Freissmuth, Walter Sandtner","doi":"10.1124/molpharm.124.000881","DOIUrl":"10.1124/molpharm.124.000881","url":null,"abstract":"<p><p>The antidepressants trazodone and nefazodone were approved some 4 and 3 decades ago, respectively. Their action is thought to be mediated, at least in part, by inhibition of the serotonin transporter [SERT/solute carrier (SLC)-6A4]. Surprisingly, their mode of action on SERT has not been characterized. Here, we show that, similar to the chemically related drug vilazodone, trazodone and nefazodone are allosteric ligands: trazodone and nefazodone inhibit uptake by and transport-associated currents through SERT in a mixed-competitive and noncompetitive manner, respectively. Contrary to noribogaine and its congeners, all three compounds preferentially interact with the Na⁺-bound outward-facing state of SERT. Nevertheless, they act as pharmacochaperones and rescue the folding-deficient variant SERT-P601A/G602A. The vast majority of disease-associated point mutations of SLC6 family members impair folding of the encoded transporter proteins. Our findings indicate that their folding defect can be remedied by targeting allosteric sites on SLC6 transporters. SIGNIFICANCE STATEMENT: The serotonin transporter is a member of the solute carrier-6 family and is the target of numerous antidepressants. Trazodone and nefazodone have long been used as antidepressants. Here, this study shows that their inhibition of the serotonin transporter digressed from the competitive mode seen with other antidepressants. Trazodone and nefazodone rescued a folding-deficient variant of the serotonin transporter. This finding demonstrates that folding defects of mutated solute carrier-6 family members can also be corrected by allosteric ligands.</p>","PeriodicalId":18767,"journal":{"name":"Molecular Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141071529","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":"Mechanistic Understanding of Dexamethasone-Mediated Protection against Remdesivir-Induced Hepatotoxicity.","authors":"Kaiyan Liu, Zhihui Li, Linhao Li, Scott Heyward, Shelley R Wang, Ling He, Hongbing Wang","doi":"10.1124/molpharm.124.000894","DOIUrl":"10.1124/molpharm.124.000894","url":null,"abstract":"<p><p>Remdesivir (RDV), a broad-spectrum antiviral agent, is often used together with dexamethasone (DEX) for hospitalized COVID-19 patients requiring respiratory support. Potential hepatic adverse drug reaction is a safety concern associated with the use of RDV. We previously reported that DEX cotreatment effectively mitigates RDV-induced hepatotoxicity and reduces elevated serum alanine aminotransferase and aspartate aminotransferase levels in cultured human primary hepatocytes (HPH) and hospitalized COVID-19 patients, respectively. Yet, the precise mechanism behind this protective drug-drug interaction remains largely unknown. Here, we show that through the activation of p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinases 1 and 2 (ERK1/2) signaling, RDV induces apoptosis (cleavage of caspases 8, 9, and 3), autophagy (increased autophagosome and LC3-II), and mitochondrial damages (decreased membrane potential, respiration, ATP levels, and increased expression of Bax and the released cytosolic cytochrome C) in HPH. Importantly, cotreatment with DEX partially reversed RDV-induced apoptosis, autophagy, and cell death. Mechanistically, DEX deactivates/dephosphorylates p38, JNK, and ERK1/2 signaling by enhancing the expression of dual specificity protein phosphatase 1 (DUSP1), a mitogen-activated protein kinase (MAPK) phosphatase, in a glucocorticoid receptor (GR)-dependent manner. Knockdown of GR in HPH attenuates DEX-mediated DUSP1 induction, MAPK dephosphorylation, as well as protection against RDV-induced hepatotoxicity. Collectively, our findings suggest a molecular mechanism by which DEX modulates the GR-DUSP1-MAPK regulatory axis to alleviate the adverse actions of RDV in the liver. SIGNIFICANCE STATEMENT: The research uncovers the molecular mechanisms by which dexamethasone safeguards against remdesivir-associated liver damage in the context of COVID-19 treatment.</p>","PeriodicalId":18767,"journal":{"name":"Molecular Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141071442","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":"Memorial Tribute to William Albert Catterall (1946-2024).","authors":"Lori L Isom","doi":"10.1124/molpharm.124.000940","DOIUrl":"https://doi.org/10.1124/molpharm.124.000940","url":null,"abstract":"","PeriodicalId":18767,"journal":{"name":"Molecular Pharmacology","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419890","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}