SLAS Discovery最新文献

{"title":"Optimization and development of a high-throughput TR-FRET screening assay for SLIT2/ROBO1 interaction","authors":"Somaya A. Abdel-Rahman ,&nbsp;Moustafa T. Gabr","doi":"10.1016/j.slasd.2025.100240","DOIUrl":"10.1016/j.slasd.2025.100240","url":null,"abstract":"<div><div>The SLIT2/ROBO1 signaling axis plays a critical role in cell migration, angiogenesis, and immune regulation, contributing to tumor progression, metastasis, and therapy resistance. SLIT2 is highly expressed in various malignancies, where it promotes immune evasion by recruiting tumor-associated macrophages and disrupting vascular integrity, ultimately diminishing therapeutic efficacy. Beyond cancer, SLIT2/ROBO1 is implicated in neural development, fibrosis, and vascular remodeling, making it a potential but underexplored therapeutic target. However, no small-molecule inhibitors of SLIT2/ROBO1 interaction currently exist. Herein, we describe the development and optimization of a time-resolved fluorescence resonance energy transfer (TR-FRET) assay for high-throughput screening of small-molecule inhibitors targeting this pathway. Using recombinant SLIT2 and ROBO1, we established a robust assay that enables high-throughput screening (HTS) of chemical libraries of small molecules for SLIT2/ROBO1 inhibition. Screening a focused chemical library of protein-protein interaction (PPI) inhibitors identified SMIFH2 as a SLIT2/ROBO1 inhibitor, demonstrating its ability to disrupt the interaction in a dose-dependent manner. Our study introduces a novel screening platform for identifying small molecule inhibitors of SLIT2/ROBO1, laying the foundation for future drug discovery efforts aimed at targeting this signaling axis in cancer and other diseases.</div></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"34 ","pages":"Article 100240"},"PeriodicalIF":2.7,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parallel in vitro ion channel and in vivo zebrafish assaying of elapid snake venoms following chromatographic separation of toxin components","authors":"Arif Arrahman ,&nbsp;Haifeng Xu ,&nbsp;Muzaffar A. Khan ,&nbsp;Tijmen S. Bos ,&nbsp;Julien Slagboom ,&nbsp;Guus C. van der Velden ,&nbsp;Ulrike Nehrdich ,&nbsp;Nicholas R. Casewell ,&nbsp;Michael K. Richardson ,&nbsp;Christian Tudorache ,&nbsp;Fernanda C. Cardoso ,&nbsp;Jeroen Kool","doi":"10.1016/j.slasd.2025.100239","DOIUrl":"10.1016/j.slasd.2025.100239","url":null,"abstract":"<div><div>Snake venoms are complex bioactive mixtures designed to paralyse, kill, or digest prey. These venoms are of pharmacological interest due to their ability to modulate molecular targets such as ion channels and receptors with high specificity and potency. Traditional studies often focus on <em>in vitro</em> molecular analysis or <em>in vivo</em> behavioural effects, limiting comprehensive understanding. Here, we present a high-throughput screening platform that combines <em>in vitro</em> ion channel assays with <em>in vivo</em> zebrafish larval bioassays using nanofractionation analytics. This method integrates post-column calcium flux assays, zebrafish paralytic bioassays, toxin mass spectrometry, and proteomics to link bioactivity with toxin identification. Using elapid snake venoms (genus <em>Dendroaspis, Naja</em>, and <em>Hemachatus</em>) as a proof of concept, we identified several toxins modulating ion channels with paralytic effects on zebrafish larvae. Our approach enables parallel acquisition of <em>in vitro</em> and <em>in vivo</em> data, offering a robust guide for identifying and characterising ion channel modulators with defined molecular targets.</div></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"34 ","pages":"Article 100239"},"PeriodicalIF":2.7,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144026241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperphosphorylated tau-based Alzheimer’s Disease drug discovery: Identification of inhibitors of tau aggregation and cytotoxicity","authors":"Hsiao-Tien Hagar ,&nbsp;Virneliz Fernandez-Vega ,&nbsp;Kuang-Wei Wang ,&nbsp;Luis M. Ortiz Jordan ,&nbsp;Justin Shumate ,&nbsp;Louis Scampavia ,&nbsp;April Sweet Tapayan ,&nbsp;Hien M Nguyen ,&nbsp;Timothy P. Spicer ,&nbsp;Min-Hao Kuo","doi":"10.1016/j.slasd.2025.100235","DOIUrl":"10.1016/j.slasd.2025.100235","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is a neurodegenerative disorder that affects more than 30 million people worldwide. Underlying the progressive decline of cognitive functions are the neurofibrillary tangles (NFTs) in neurons of the brain. The spatiotemporal distribution of NFTs predicts the progression of cognitive symptoms. In contrast, the senile plaques of amyloid-β aggregates, another major biomarker for AD, do not correlate with the clinical symptom development, consistent with the negligible benefits to cognitive functions in patients receiving anti-Aβ immunotherapies. A new drug discovery avenue targeting tau pathologies is therefore urgently needed. Using a recombinant hyperphosphorylated tau (p‐tau) that presents characters key to the disease, e.g., formation of neurotoxic aggregates, we conducted a fluorescence p-tau aggregation assay and completed a 100K-compound high-throughput screen (HTS) and identified inhibitors of p-tau aggregation and cytotoxicity. This dual functional screen resulted in several potent compounds that effectively curbed both p-tau aggregation and cytotoxicity. Results presented in this work are the first HTS for small-molecule compounds that target the cellular toxicity of hyperphosphorylated tau. Top hits found in this screen and their analogues to be developed in the near future may lead to breakthroughs in the therapeutic development for Alzheimer’s disease and other neurodegenerative tauopathies.</div></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"33 ","pages":"Article 100235"},"PeriodicalIF":2.7,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of a high-throughput TR-FRET assay to identify inhibitors of the FAK-paxillin protein-protein interaction","authors":"Rukayat Aromokeye ,&nbsp;Martha Ackerman-Berrier ,&nbsp;Rosa del Carmen Araujo ,&nbsp;Maria Lambousis ,&nbsp;Savio Cardoza ,&nbsp;L. Charlie Chen ,&nbsp;Matthew E. Kaplan ,&nbsp;Haining Zhu ,&nbsp;Celina Zerbinatti ,&nbsp;Christopher Penton ,&nbsp;Gregory R.J. Thatcher ,&nbsp;Timothy Marlowe","doi":"10.1016/j.slasd.2025.100237","DOIUrl":"10.1016/j.slasd.2025.100237","url":null,"abstract":"<div><div>Focal Adhesion Kinase (FAK) is a non-receptor tyrosine kinase and scaffolding protein that is primarily regulated by integrin signaling. FAK signaling increases cell motility in both normal and cancer cells, and FAK is often overexpressed and/or dysregulated in many types of cancer. FAK has three different domains: an N-terminal FERM domain, a central kinase domain (the traditional target for drug discovery), and a C-terminal focal adhesion targeting (FAT) domain. The FAT domain represents an alternative approach to targeting FAK, and our aim is to identify novel small molecules that will inhibit FAT protein-protein interactions (PPI), which may have implications for cancer and fibrosis treatment. Here, we describe the development and validation of a robust high-throughput screening (HTS) assay suitable for identifying inhibitors of the FAT:paxillin PPI. The 384-well low volume assay is based on time-resolved fluorescence resonance energy transfer (TR-FRET) technology and uses the high affinity biotin-PEG-1907 stapled peptide to mimic paxillin. We also present the development of a TR-FRET counterscreen assay using CD47 and SIRPα to detect nonspecific inhibitors, as well as an orthogonal surface plasmon resonance (SPR) binding assay. We employed the FAT: biotin-PEG-1907 assay to screen a 31,636-compound small molecule library. Primary positives (hits) from HTS were confirmed in concentration-response primary and counterscreen assays and validated in the SPR binding assay. We discovered 4 inhibitors of the FAT:paxillin PPI using this approach and established a framework for small molecule drug discovery efforts targeting the FAT domain of FAK.</div></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"34 ","pages":"Article 100237"},"PeriodicalIF":2.7,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143927492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A biochemical screening platform to target chromatin states using condensates as a tool","authors":"Laura J. Hsieh ,&nbsp;Tracy Lou ,&nbsp;Muryam A. Gourdet ,&nbsp;Emily Wong ,&nbsp;Geeta J. Narlikar","doi":"10.1016/j.slasd.2025.100236","DOIUrl":"10.1016/j.slasd.2025.100236","url":null,"abstract":"<div><div>Chromatin states define cell fates and consequently dysfunctional chromatin states drive disease. Conventional approaches to target dysfunctional chromatin states typically rely on targeting a defined, structured binding pocket of a specific chromatin protein. However, drugs developed from targeting single chromatin proteins have often failed in the clinic due to toxicity from broad non-specific effects on the genome. Substantial previous work has indicated that the function of a given chromatin state is encoded in the context-dependent protein-protein interactions (PPIs) between the Intrinsically disordered regions (IDRs) and folded domains of the multiple constituents. Currently, there are no drug discovery approaches that target the complex multivalent protein interactions within a given dysfunctional chromatin state. Therefore, new methods are required to target chromatin within specific conformational contexts for better translation into humans. Prior discoveries from our group and others have shown that chromatin intrinsically forms condensates through weak, yet specific, multivalent interactions between itself and other components. Using this intrinsic property of chromatin, we have developed a new screening method to address this technology gap and identify modulators of dysfunctional chromatin states for drug discovery. Here, we show that we can recreate different chromatin contexts as phase-separated condensates that have distinct biochemical and biophysical properties. Furthermore, we have scaled the technology into a screening platform and identify small molecules that modulate chromatin states specifically based on their chromatin context. We anticipate that such specific targeting of a disease driving chromatin assembly would reduce off-target effects, translate better into humans and open a new landscape of therapeutic possibilities for targeting complex, multivalent interactions.</div></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"33 ","pages":"Article 100236"},"PeriodicalIF":2.7,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143902437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing the development of TRIP13 inhibitors: A high-throughput screening approach","authors":"Rae M. Sammons ,&nbsp;Soma Ghosh ,&nbsp;Lacin Yapindi ,&nbsp;Eun Jeong Cho ,&nbsp;Faye M. Johnson ,&nbsp;Kevin N. Dalby","doi":"10.1016/j.slasd.2025.100233","DOIUrl":"10.1016/j.slasd.2025.100233","url":null,"abstract":"<div><div>TRIP13, a promising target for cancer therapy, has been identified as a key regulator of the mitotic checkpoint. Overexpression of TRIP13 is associated with poor clinical outcomes in various cancers. Inhibition of TRIP13 has the potential to address therapeutic challenges in cancer, particularly in therapy-resistant and Rb-deficient cancers. Despite the potential therapeutic benefits of TRIP13 inhibition, the development of TRIP13 inhibitors has been hindered by the lack of a robust high-throughput screening (HTS) assay.</div><div>We developed a luminescence-based biochemical assay for TRIP13 activity to address this challenge using the ADP-Glo detection system. This assay offers high sensitivity, low background signal, and ease of automation, making it ideal for HTS applications. A pilot screen of kinase-focused inhibitors library and a large-scale screen of 4000 additional compounds demonstrated the assay's robust performance with a z'-factor exceeding 0.85 and a signal-to-background (S/B) ratio near 6. From the 50 initial hits, rigorous validation identified anlotinib as the most potent TRIP13 inhibitor with an IC₅₀ of 5 μM. A cellular thermal shift assay (CETSA) confirmed the direct binding of anlotinib to TRIP13, validating the potential of our biochemical assay for identifying novel TRIP13 inhibitors. Our study provides a valuable tool for discovering novel TRIP13 inhibitors and advances our understanding of the therapeutic potential of targeting TRIP13 in cancer.</div></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"33 ","pages":"Article 100233"},"PeriodicalIF":2.7,"publicationDate":"2025-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combinatorial screen with apoptosis pathway targeted agents alrizomadlin, pelcitoclax, and dasminapant in multi-cell type tumor spheroids","authors":"Nathan P. Coussens ,&nbsp;Thomas S. Dexheimer ,&nbsp;Thomas Silvers ,&nbsp;Phillip R. Sanchez ,&nbsp;Li Chen ,&nbsp;Melinda G. Hollingshead ,&nbsp;Naoko Takebe ,&nbsp;James H. Doroshow ,&nbsp;Beverly A. Teicher","doi":"10.1016/j.slasd.2025.100230","DOIUrl":"10.1016/j.slasd.2025.100230","url":null,"abstract":"<div><div>Apoptosis, or programmed cell death, plays a critical role in maintaining tissue homeostasis by eliminating damaged or abnormal cells. Dysregulation of apoptosis pathways is a hallmark of cancer, allowing malignant cells to evade cell death and proliferate uncontrollably. Targeting apoptosis pathways has emerged as a promising therapeutic strategy in cancer treatment, aiming to restore the balance between cell survival and death. The MDM2 inhibitor alrizomadlin, the Bcl-2/Bcl-xL inhibitor pelcitoclax, and the IAP family inhibitor dasminapant were evaluated both individually and in combinations with standard of care and investigational anticancer small molecules in a spheroid model of solid tumors. The multi-cell type tumor spheroids were grown from human endothelial cells and mesenchymal stem cells combined with human malignant cells that were either established or patient-derived cell lines from the NCI Patient-Derived Models Repository. The malignant cell lines were derived from a range of solid tumors including uterine carcinosarcoma, synovial sarcoma, rhabdomyosarcoma, soft tissue sarcoma, malignant fibrous histiocytoma, malignant peripheral nerve sheath tumor (MPNST), pancreas, ovary, colon, breast, and small cell lung cancer. Interactions were observed from combinations of the apoptosis pathway targeted agents. Additionally, interactions were observed from combinations of the apoptosis pathway targeted agents with other agents, including PARP inhibitors, the XPO1 inhibitor eltanexor, and the PI3K inhibitor copanlisib. Enhanced activity was also observed from combinations of the apoptosis pathway targeted agents with MAPK pathway targeted agents, including the MEK inhibitor cobimetinib as well as adagrasib and MRTX1133, which specifically target the KRAS G12C and G12D variants, respectively.</div></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"33 ","pages":"Article 100230"},"PeriodicalIF":2.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143859651","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antimicrobial resistance: Linking molecular mechanisms to public health impact","authors":"Ghazala Muteeb ,&nbsp;Raisa Nazir Ahmed Kazi ,&nbsp;Mohammad Aatif ,&nbsp;Asim Azhar ,&nbsp;Mohamed El Oirdi ,&nbsp;Mohd Farhan","doi":"10.1016/j.slasd.2025.100232","DOIUrl":"10.1016/j.slasd.2025.100232","url":null,"abstract":"<div><h3>Background</h3><div>Antimicrobial resistance (AMR) develops into a worldwide health emergency through genetic and biochemical adaptations which enable microorganisms to resist antimicrobial treatment. β-lactamases (blaNDM, blaKPC) and efflux pumps (MexAB-OprM) working with mobile genetic elements facilitate fast proliferation of multidrug-resistant (MDR) and exttreme drug-resistant (XDR) phenotypes thus creating major concerns for healthcare systems and community health as well as the agricultural sector.</div></div><div><h3>Objectives</h3><div>The review dissimilarly unifies molecular resistance pathways with public health implications through the study of epidemiological data and monitoring approaches and innovative therapeutic solutions. Previous studies separating their attention between molecular genetics and clinical outcomes have been combined into our approach which delivers an all-encompassing analysis of AMR.</div></div><div><h3>Key insights</h3><div>The report investigates the resistance mechanisms which feature enzymatic degradation and efflux pump overexpression together with target modification and horizontal gene transfer because these factors represent important contributors to present-day AMR developments. This review investigates AMR effects on hospital and community environments where it affects pathogens including MRSA, carbapenem-resistant Klebsiella pneumoniae, and drug-resistant <em>Pseudomonas aeruginosa</em>. This document explores modern AMR management methods that comprise WHO GLASS molecular surveillance systems and three innovative strategies such as CRISPR-modified genome editing and bacteriophage treatments along with antimicrobial peptides and artificial intelligence diagnostic tools.</div></div><div><h3>Conclusion</h3><div>The resolution of AMR needs complete scientific and global operational methods alongside state-of-the-art therapeutic approaches. Worldwide management of drug-resistant infection burden requires both enhanced infection prevention procedures with next-generation antimicrobial strategies to reduce cases effectively.</div></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"33 ","pages":"Article 100232"},"PeriodicalIF":2.7,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Empowering research in chemical biology and early drug discovery – an update from the European research infrastructure EU-OPENSCREEN","authors":"Robert K. Harmel ,&nbsp;Tanja Miletic ,&nbsp;Katja Herzog ,&nbsp;Bahne Stechmann","doi":"10.1016/j.slasd.2025.100228","DOIUrl":"10.1016/j.slasd.2025.100228","url":null,"abstract":"<div><div>EU-OPENSCREEN is the European research infrastructure consortium for chemical biology and early drug discovery. It provides open access to high-throughput screening, chemoproteomics and spatial MS-based omics platforms and medicinal chemistry groups to support the discovery of new biologically active small molecules that act as starting points for the development of new chemical tool compounds and drugs. Since its inauguration in 2018, the research infrastructure evolved from a blueprint to a fully operational platform. As new trends and technologies have an important impact on modern drug discovery, EU-OPENSCREEN continuously expands and refines its portfolio of technologies and expertise. In this perspective, the key achievements of the past six years and the planned activities over the next years are described. We illustrate how scientists can benefit from EU-OPENSCREEN through gaining access to technology platforms and expertise to unlock the extraordinary potential of their research projects and translate them into novel, impactful and innovative applications.</div></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"32 ","pages":"Article 100228"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ATPase activity profiling of three human DExD/H-box RNA helicases","authors":"Fengling Li ,&nbsp;U Hang Chan ,&nbsp;Julia Garcia Perez ,&nbsp;Hong Zeng ,&nbsp;Irene Chau ,&nbsp;Yanjun Li ,&nbsp;Almagul Seitova ,&nbsp;Levon Halabelian","doi":"10.1016/j.slasd.2025.100229","DOIUrl":"10.1016/j.slasd.2025.100229","url":null,"abstract":"<div><div>Human DExD/H-box RNA helicases are ubiquitous molecular motors that unwind and rearrange RNA secondary structures in an ATP-dependent manner. These enzymes play essential roles in nearly all aspects of RNA metabolism. While their biological functions are well-characterized, the kinetic mechanisms remain relatively understudied <em>in vitro</em>. In this study, we describe the development and optimization of a bioluminescence-based assay to characterize the ATPase activity of three human RNA helicases: MDA5, LGP2, and DDX1. The assays were conducted using annealed 24-mer ds-RNA (blunt-ended double-stranded RNA) or double-stranded RNA with a 25-nt 3ʹ overhang (partial ds-RNA). These findings establish a robust and high-throughput <em>in vitro</em> assay suitable for a 384-well format, enabling the discovery and characterization of inhibitors targeting MDA5, LGP2, and DDX1. This work provides a valuable resource for advancing our understanding of these helicases and their therapeutic potential in Alzheimer's disease.</div></div>","PeriodicalId":21764,"journal":{"name":"SLAS Discovery","volume":"32 ","pages":"Article 100229"},"PeriodicalIF":2.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}