Molecular Pharmaceutics最新文献

{"title":"⁶⁴Cu Radiolabeled PDGFRβ-Targeting Affibody for PET Imaging in Pancreatic Cancer.","authors":"Zhao Li, Ruiman Geng, Yousheng Zhan, Ruomeng Liu, Mufeng Li, Nengwen Ke, Hao Yang, Xiaofeng Lu, Lin Li, Suping Li, Huawei Cai","doi":"10.1021/acs.molpharmaceut.4c01368","DOIUrl":"10.1021/acs.molpharmaceut.4c01368","url":null,"abstract":"<p><p>Pancreatic cancer is a malignant solid tumor that contains a significant number of cancer-associated fibroblasts (CAFs). Clinical trials have confirmed that CAF-targeted radionuclide therapy can suppress tumor growth and extend the survival of patients; therefore, quantifying CAFs by molecular imaging of CAF biomarkers is helpful for assessing disease progression and therapeutic responses of pancreatic cancer. In our previous study, we found that platelet-derived growth factor receptor beta (PDGFRβ) was highly expressed on various fibroblast cells, and a novel affibody (Z_PDGFRβ) with highly specific binding to PDGFRβ had been developed. Herein, we verified the high expression of PDGFRβ on CAFs in pancreatic cancer tissues, and the Z_PDGFRβ affibody was radiolabeled with ⁶⁴Cu to obtain a [⁶⁴Cu]Cu-NOTA-Z_PDGFRβ conjugate with radiochemical purity higher than 95%. Biodistribution studies showed that tumor uptake of [⁶⁴Cu]Cu-NOTA-Z_PDGFRβ reached the peak of 7.28 ± 0.92 at 6 h postinjection, and the tumor-to-pancreas ratio continuously increased to reach the peak of 25.9 ± 8.18 at 24 h postinjection. Positron emission tomography (PET) imaging with [⁶⁴Cu]Cu-NOTA-Z_PDGFRβ showed ideal tumor uptake and imaging capability in mice bearing both subcutaneous xenografts and <i>in situ</i> grafts. Our results demonstrated that the [⁶⁴Cu]Cu-NOTA-Z_PDGFRβ conjugate could be applied as a promising PDGFRβ-targeted radiotracer for PET imaging of pancreatic cancer.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"1633-1640"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143431972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights from Computational Studies of Polymeric Systems for Nucleic Acid Delivery.","authors":"Jesse Dylan Ziebarth, Hossain Shadman, Yongmei Wang","doi":"10.1021/acs.molpharmaceut.4c00994","DOIUrl":"10.1021/acs.molpharmaceut.4c00994","url":null,"abstract":"<p><p>The safe and efficient delivery of nucleic acids into cells is a critical step in the success of gene and cell therapies. Although viral vectors are the predominant tools in current gene and cell therapy practices, they present significant challenges including high costs and safety concerns. Nonviral delivery systems for nucleic acids show immense potential for future medicine, particularly as nucleic acid therapeutics continue to be developed for the treatment of a wide range of diseases, including cancer. Significant research efforts, both experimental and computational, have been devoted to the development, characterization, and understanding of nonviral delivery processes. While numerous reviews have documented these research advancements, few have specifically addressed the contributions from computational studies. In this review, we provide an overview of the insights gained from computational and theoretical studies of polymeric systems for nucleic acid delivery. We also highlight future directions where computational and experimental approaches could synergize to advance the field.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"1160-1173"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143431977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Large-Scale Compartmental Model-Based Study of Preclinical Pharmacokinetic Data and Its Impact on Compound Triaging in Drug Discovery.","authors":"Peter Zhiping Zhang, Jeanine Ballard, Facundo Esquivel Fagiani, Dustin Smith, Christopher Gibson, Xiang Yu","doi":"10.1021/acs.molpharmaceut.4c00813","DOIUrl":"10.1021/acs.molpharmaceut.4c00813","url":null,"abstract":"<p><p>Reliable and robust human dose prediction plays a pivotal role in drug discovery. The prediction of human dose requires proper modeling of preclinical intravenous (IV) pharmacokinetic (PK) data, which is usually achieved either through noncompartmental analysis (NCA) or compartmental analysis. While NCA is straightforward, it loses valuable information about the shape of the PK curves. In contrast, compartmental analysis offers a more comprehensive interpretation but poses challenges in scaling up for high-throughput applications in discovery. To address this challenge, we developed computational frameworks, termed compartmental PK (CPK) and automated dose prediction (ADP), to enable automated compartmental model-based IV PK data modeling, translation, and simulation for human dose prediction in compound triaging and optimization. With CPK and ADP, we analyzed compounds with data collected at the MRL between 2013 and 2023 to quantitatively characterize the impact of different PK modeling and simulation methods on human dose prediction. Our study revealed that despite minimal impact on estimating animal PK parameters, different methods significantly impacted predicted human dose, exposure, and Cmax, driven more by different simulation assumptions than by the PK modeling itself. CPK-ADP therefore enables us to efficiently perform complex human dose predictions on a large scale while integrating the latest and best information available on absorption, distribution, and clearance to support decision-making in discovery.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"1230-1240"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral DNA Vaccine Utilizing the Yeast Cell Wall for Dectin-1 Receptor-Mediated Enhancement of Mucosal Immunity.","authors":"Yingqi Liu, Fan Meng, Wanting Feng, Zehong Chen, Haonan Xing, Aiping Zheng","doi":"10.1021/acs.molpharmaceut.4c00943","DOIUrl":"10.1021/acs.molpharmaceut.4c00943","url":null,"abstract":"<p><p>Mucosal vaccines can generate localized mucosal immunity, effectively preventing initial pathogen infection and providing more effective protection. Oral vaccines are an attractive option for inducing mucosal immunity. The yeast cell wall, primarily composed of natural β-1,3-d glucan, can be recognized by the apical membrane receptor, dectin-1, which has a high expression on macrophages and intestinal M cells. In this study, by using vortexing methods to break yeast cell walls into nanometer-sized fragments, which retain the negatively charged β-glucan components on their surface and employing electrostatic adsorption/coextrusion techniques, these fragments were attached onto the surface of PS-DNA NPs, as verified by a scanning electron microscope (SEM), a transmission electron microscope (TEM), and dynamic light scattering (DLS) data. YCW-coated NPs (YNPs) showed greater drug stability compared to NPs in a simulated gastrointestinal environment. In vitro cell evaluation further demonstrated that YNPs were rapidly and efficiently taken up by antigen-presenting cells via receptor dectin-1-mediated endocytosis. In vivo experiments revealed that the oral vaccine elicited high levels of RBD-specific antibodies and triggered extensive cellular immunity in the intestinal mucosa. This study provides new insights into mucosal vaccine research.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"1241-1252"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143439391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Verticillin A-Loaded Surgical Buttresses Prevent Local Pancreatic Cancer Recurrence in a Murine Model.","authors":"Zeinab Y Al Subeh, Herma C Pierre, Cedric J Pearce, Mark W Grinstaff, Aaron H Colby, Kebin Liu, Nicholas H Oberlies","doi":"10.1021/acs.molpharmaceut.4c00589","DOIUrl":"10.1021/acs.molpharmaceut.4c00589","url":null,"abstract":"<p><p>The fungal metabolite verticillin A is a potent and selective histone methyltransferase inhibitor. It regulates apoptosis, the cell cycle, and stress response, and displays potent activity in the suppression of tumor cell growth in several different in vivo models. Verticillin A sensitizes pancreatic cancer cells to anti-PD-1 immunotherapy by regulating PD-L1 expression. However, as with many natural products, delivery and systemic toxicity are challenges that must be overcome to advance their use as a chemotherapeutic. To both reduce systemic toxicity and improve delivery, we report a verticillin A-loaded surgical buttress, which is well-tolerated at a dose as high as 40 mg/kg. In contrast, free verticillin A administered systemically results in toxicity at a dose of 3 mg/kg. The verticillin A-loaded buttress suppresses tumor recurrence in vivo in a safe and dose-dependent manner against a highly aggressive and metastatic model of pancreatic cancer.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"1220-1229"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143044921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of Novel Peptide-Based Radiotracers for Detecting FGL1 Expression in Tumors.","authors":"Yue Xu, Jinyuan Zhang, Donghui Pan, Junjie Yan, Chongyang Chen, Lizhen Wang, Xinyu Wang, Min Yang, Yuping Xu","doi":"10.1021/acs.molpharmaceut.4c01293","DOIUrl":"10.1021/acs.molpharmaceut.4c01293","url":null,"abstract":"<p><p>A novel immune checkpoint, FGL1, is a potentially viable target for tumor immunotherapy. The development of FGL1-targeted PET probes could provide significant insights into the immune system's status and the evaluation of treatment efficacy. A ClusPro 2.0 server was used to analyze the interaction between FGL1 and LAG3, and the candidate peptides were identified by using the Rosetta peptide derivate protocol. Three candidate peptides targeting FGL1, named FGLP21, FGLP22, and FGLP23, with a simulated affinity of -9.56, -8.55, and -8.71 kcal/mol, respectively, were identified. The peptides were readily conjugated with p-NCS-benzyl-NODA-GA, and the resulting compounds were successfully labeled with ⁶⁸Ga in approximately 70% yields and radiochemical purity greater than 95%. In vitro competitive cell-binding assay demonstrated that all probes bound to FGL1 with IC₅₀ ranging from 100 nM to 160 nM. Among the probes, PET imaging revealed that ⁶⁸Ga-NODA-FGLP21 exhibited the best tumor imaging performance in mice bearing FGL1 positive Huh7 tumor. At 60 min p.i., the tumor uptake of ⁶⁸Ga-NODA-FGLP21 was significantly higher than those of ⁶⁸Ga-NODA-FGLP22 and ⁶⁸Ga-NODA-FGLP23, respectively (2.51 ± 0.11% ID/g vs 1.00 ± 0.16% ID/g and 1.49 ± 0.05% ID/g). Simultaneously, the tumor-to-muscle uptake ratios of the former were also higher than those of the latter, respectively (19.40 ± 2.30 vs 9.65 ± 0.62 and 12.45 ± 0.72). In the presence of unlabeled FGLP21, the uptake of ⁶⁸Ga-NODA-FGLP21 in Huh7 xenograft decreased to 0.81 ± 0.09% ID/g at 60 min p.i., which is similar to that observed in the FGL1 negative U87 MG tumor (0.46 ± 0.03% ID/g). The results were consistent with the immunohistochemical analysis and ex vivo autoradiography. No significant radioactivity was accumulated in normal organs, except for kidneys. In summary, a preclinical study confirmed that the tracer ⁶⁸Ga-NODA-FGLP21 has the potential to specifically detect FGL1 expression in tumors with good contrast to the background.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"1605-1614"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143077954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New PPARα Agonist A190-Loaded Microemulsion for Chemotherapy-Induced Peripheral Neuropathy.","authors":"Rudra Pangeni, Surendra Poudel, Sara M Herz, Grant Berkbigler, Adam S Duerfeldt, M Imad Damaj, Qingguo Xu","doi":"10.1021/acs.molpharmaceut.4c01374","DOIUrl":"10.1021/acs.molpharmaceut.4c01374","url":null,"abstract":"<p><p>Chemotherapy-induced peripheral neuropathy (CIPN) is a serious side effect of anticancer agents with limited effective preventive or therapeutic interventions. Although fenofibrate, a peroxisome proliferator-activated receptor-alpha (PPARα) agonist, has demonstrated neuroprotective and analgesic properties, its clinical utility is hindered by low receptor affinity, poor subtype selectivity, and suboptimal bioavailability. A190, a highly selective and potent nonfibrate PPARα agonist, offers a promising alternative but is limited by poor aqueous solubility, resulting in reduced oral bioavailability and therapeutic efficacy. To address these limitations, an optimized oil-in-water (o/w) microemulsion formulation was developed using Box-Behnken design to enhance the solubility and intestinal permeability of A190. The A190 microemulsion exhibited physical stability with a droplet size of approximately 100 nm and a drug loading efficiency of greater than 95%. The effective and apparent permeability of A190 from the microemulsion was significantly higher compared to that of free A190 dispersion, respectively. Additionally, no significant impact on the cell viability was observed, indicating less toxicity and a good biocompatibility of the formulation components. The oral bioavailability of A190 microemulsion was approximately 5-fold higher compared to A190 dispersion, demonstrating the microemulsion's potential to greatly enhance the oral bioavailability of hydrophobic drugs. Furthermore, our findings reveal that orally administered A190 microemulsion effectively reduced CIPN-induced mechanical hypersensitivity, likely mediated through PPARα activation. A190 microemulsion was found to be equally effective at reducing the chronic inflammatory complete Freund's adjuvant-induced pain. These results underscore A190s potential as a nonopioid therapeutic candidate, utilizing a novel microemulsion formulation for the management of chemotherapy-induced neuropathic pain and chronic inflammatory pain.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"1641-1656"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical Evaluation of ⁶⁸Ga-Labeled SL1 Aptamer for c-Met Targeted PET Imaging.","authors":"Xuwei Liu, Yamei Chen, Fengsheng Zhang, Fengshuang Qiu, Xiaoping Xu, Jianping Zhang, Simin He, Ding Ding, Weihong Tan, Shaoli Song","doi":"10.1021/acs.molpharmaceut.4c01344","DOIUrl":"10.1021/acs.molpharmaceut.4c01344","url":null,"abstract":"<p><p>Tyrosine protein kinase c-Met, encoded by the Met gene, is a membrane-associated receptor tyrosine kinase that is often aberrantly expressed in a wide range of tumors. The development of imaging probes specifically targeting c-Met is critical for improving cancer diagnostics. In this study, we successfully designed and fabricated an aptamer molecular imaging probe ([⁶⁸Ga]Ga-NOTA-SL1) with high radiochemical purity (RCP), good stability <i>in vitro</i>, and high affinity for c-Met expressed tumors. As shown by the micro-PET/CT scanning, [⁶⁸Ga]Ga-NOTA-SL1 efficiently imaged tumor models with varying c-Met expression. The quantitative analysis of micro-PET/CT showed tumor uptake of [⁶⁸Ga]Ga-NOTA-SL1 in the HCC827 tumor models (30 min, 2.93 ± 0.64%ID/g; 60 min, 2.03 ± 0.67%ID/g; 90 min, 1.63 ± 0.61%ID/g), PC-9 tumor models (30 min, 2.1 ± 0.72%ID/g; 60 min, 1.7 ± 0.56%ID/g; 90 min, 1.33 ± 0.38%ID/g), and HCT116 tumor models (30 min, 1.4 ± 0.17%ID/g; 60 min, 1.23 ± 0.15%ID/g; 90 min, 0.97 ± 0.21%ID/g). The results of immunohistochemistry (IHC) further confirmed the targeting ability of [⁶⁸Ga]Ga-NOTA-SL1 to c-Met from a molecular pathological perspective. The probe effectively imaged c-Met-positive tumors and demonstrated a favorable metabolism profile and targeting performance in non-small cell lung cancer (NSCLC) or colorectal cancer tumor models. Consequently, this probe shows promise as an imaging agent capable of providing valuable diagnostic insights into tumors with aberrant c-Met expression.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"1615-1623"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143389517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Microemulsion Oil Components on Liquid-Liquid Phase Separation of a Supersaturated Drug Revealed by Cryo-TEM and ¹H NMR Analysis.","authors":"Risa Edera, Keisuke Ueda, Saeko Tomita, Kenjirou Higashi, Kunikazu Moribe","doi":"10.1021/acs.molpharmaceut.4c01257","DOIUrl":"10.1021/acs.molpharmaceut.4c01257","url":null,"abstract":"<p><p>Supersaturatable self-microemulsifying drug delivery system (S-SMEDDS) has recently been utilized to enhance the oral absorption of poorly water-soluble drugs. S-SMEDDS forms drug-incorporated microemulsions (MEs) during aqueous dispersion with the formation of drug supersaturation in the bulk water phase. However, the liquid-liquid phase separation (LLPS) behavior of the supersaturated drugs within MEs has not been well studied. This study investigated the impact of S-SMEDDS components on the LLPS of the supersaturated drug and the achievable supersaturation level of the drug in MEs. Fenofibrate (FFB)-loaded S-SMEDDS formulations composed of different oils, Labrafil M 1944 CS (M1944) and Labrafac PG (PG), were prepared and dispersed into water to form MEs (M1944 ME and PG ME). Cryo-TEM measurements revealed the coexistence of swelling micelles and nanosized FFB-rich droplets in highly FFB-loaded MEs, indicating that FFB underwent LLPS even in the MEs. The FFB-rich droplet size was significantly reduced in PG ME. NMR-based quantification of the solubilized FFB in swelling micelles and phase-separated FFB revealed that apparent amorphous solubility of FFB increased with increasing M1944 components in MEs, while that was almost constant regardless of PG contents. On the other hand, PG was largely partitioned into the FFB-rich phase, resulting in the reduction of the chemical potential of FFB in the FFB-rich phase and the maximum free FFB concentration in the bulk water phase. The mixing of PG with the FFB-rich phase would work to maintain the FFB-rich droplet as a smaller size. Meanwhile, M1944 was minimally distributed to the FFB-rich phase, keeping the maximum supersaturation level of FFB. This study highlights that the impact of S-SMEDDS oil components on the physicochemical properties of the drug-rich phase formed via LLPS and achievable drug supersaturation should be considered when designing S-SMEDDS formulations to enhance drug absorption.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"1539-1554"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intrinsic Differential Scanning Fluorimetry for Protein Stability Assessment in Microwell Plates.","authors":"Michaela Cohrs, Alastair Davy, Manon Van Ackere, Stefaan De Smedt, Kevin Braeckmans, Markus Epe, Hristo L Svilenov","doi":"10.1021/acs.molpharmaceut.4c01496","DOIUrl":"10.1021/acs.molpharmaceut.4c01496","url":null,"abstract":"<p><p>Intrinsic differential scanning fluorimetry (DSF) is essential for analyzing protein thermal stability. Until now, intrinsic DSF was characterized by medium throughput and high consumable costs. Here, we present a microplate-based intrinsic DSF approach that enables the measurement of up to 384 samples in parallel by consuming only 10 μL per sample. We systematically test and benchmark the new intrinsic DSF against gold-standard methods such as differential scanning microcalorimetry and circular dichroism. Using a range of model proteins and sample conditions, we demonstrate the robustness and versatility of the intrinsic DSF method for characterizing protein stability and ranking protein drug candidates. In addition, we demonstrate modulated scanning fluorimetry (MSF) capabilities on the intrinsic DSF hardware that enable simultaneous MSF measurements in 384-microwell plates. Overall, the presented technology is a powerful tool for the early stability analysis of various protein samples and drug candidates.</p>","PeriodicalId":52,"journal":{"name":"Molecular Pharmaceutics","volume":" ","pages":"1697-1706"},"PeriodicalIF":4.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}