Dominic Meusch’s Post

"High-Throughput SFC-MS/MS Method to Measure EPSA and Predict Human Permeability" (https://lnkd.in/esSNZfTG) ❗🔬Highly recommend this recent paper to all Drug Hunters🔬❗ Yue-Ting Wang, et al. introduce a novel high-throughput (HT) method for measuring experimental polar surface area (EPSA) as a surrogate for permeability assessment, especially for compounds that do not comply with Lipinski’s Rule of 5. This method leverages supercritical fluid chromatography-tandem mass spectrometry (SFC-MS/MS) to enhance sensitivity, selectivity, and data quality while significantly reducing data acquisition time. EPSA serves as a predictor for Caco-2 cell and human intestinal permeability, offering improvements over traditional topological polar surface area (TPSA) and parallel artificial membrane permeability assays (PAMPA). This new HT-EPSA method is particularly beneficial for evaluating bRo5 compounds such as proteolysis targeting chimeras (PROTACs), cyclic peptides, and macrocycles, which require conformational flexibility and intramolecular hydrogen bonding (IMHB) to optimize solubility, permeability, and target binding. The paper highlights the utility of HT-EPSA in early-stage drug discovery for rank-ordering compounds, accelerating decision-making, and predicting in vitro and in vivo human intestinal permeability, thus offering a significant advancement for medicinal chemists working on challenging drug targets.

🔬💊 Lipid Nanoparticles: A Game Changer in Drug Delivery How can we effectively deliver drugs that are insoluble in water, have strong side effects, or are extremely fragile, such as nucleic acids? The answer lies in lipid nanoparticles (LNCs), which protect active pharmaceutical ingredients (APIs) and ensure their safe transport to the target site. A new review article by researchers from CATRIN and their international collaborators, published in Molecular Pharmaceutics, summarizes the computational methods currently available for studying and designing LNCs. Special focus is given to molecular dynamics simulations, which help uncover composition–structure–function relationships of these advanced drug carriers. The study also explores the potential of machine learning to optimize LNC design for improved performance. By integrating experimental and theoretical approaches, we can enhance LNC properties, paving the way for more efficient and safer drug therapies. 📖 Read more in the full article: https://lnkd.in/eeM-QYih This work was supported by the #TECHSCALE and MINIGRAPH projects and received financial support from the Projekt Refresh. #CATRIN #LipidNanoparticles #DrugDelivery #MolecularDynamics #MachineLearning #PharmaceuticalScience Markéta Paloncýová Petra Kührová Petra Čechová Martin Šrejber Michal Otyepka Palacký University Olomouc Vysoká škola báňská - Technická univerzita Ostrava IT4Innovations National Supercomputing Center Université Claude Bernard Lyon 1

#Peptides and #DrugDiscovery – Part 4 As discussed in our previous post, advances in molecular biology led to significant breakthroughs in peptide drug discovery with the first approved peptide drugs. However, enhancing efficacy and identifying optimal peptide drugs remained challenging. Enter the 1990s-2000s, where advancements in peptide engineering made a significant impact. Stabilization techniques, such as cyclization and the incorporation of non-natural amino acids, were developed to enhance the therapeutic properties of peptides. Additionally, combinatorial chemistry and high-throughput screening technologies enabled the rapid identification and optimization of peptide candidates. These innovations paved the way for more effective and stable peptide therapeutics, marking another crucial stage in the journey of peptide drug discovery. What happened next? Stay tuned for our next post! Read our previous post here > https://lnkd.in/dkBPsVft #pharma #drugdevelopment

Studying 𝘁𝗼𝘅𝗶𝗻𝘀 is crucial for advancing our understanding of 𝗶𝗼𝗻 𝗰𝗵𝗮𝗻𝗻𝗲𝗹𝘀 and developing new drugs. Many toxins specifically target ion channels, making them invaluable tools in research and offering unique insights into ion channel structure and function. Moreover, venom-derived peptides are emerging as promising candidates for drug development, opening new avenues in pharmaceutical research. While traditional patch clamp techniques have been essential in this field, recent technological advancements have revolutionized toxin research. Automated patch clamp systems and parallel lipid bilayer recordings have dramatically improved our ability to study toxin effects on ion channels. These tools enable high-throughput screening and provide detailed mechanistic insights, accelerating the pace of discovery. At Nanion, we're proud that our instruments have contributed to numerous important discoveries in toxin research. Our technologies have been instrumental in studying a wide range of toxins, including marine, spider, scorpion, ant, bee, wasp toxins, and many more. If you're interested in how automated technologies can accelerate your toxin research, discover our recent flyer here: https://ow.ly/7mbW50UfIja or explore our dedicated webpage on toxin research and ion channels: https://ow.ly/iPoe50UfIjb #toxins #ionchannels #drugdiscovery #electrophysiology #apc

✨✨ Welcome to read the latest research "Molecular Hybridization as a Strategy for Developing #Artemisinin-Derived #Anticancer Candidates" by Dr. Maria Luisa Navacchia et al. 🔗 Paper link: https://lnkd.in/gd6yT27e Artemisinin, a natural product extracted from /Artemisa annua/ and approved as antimalarial drug, has also been explored as a potential anticancer drug. Indeed, drug repurposing is a relevant and increasingly pursued approach in the pharmaceutical sector. However, the therapeutic use of artemisinin is limited due to its poor stability and bioavailability. Molecular hybridization resulting from a covalent combination of artemisinin with one or more active pharmacophores has emerged as a promising approach to overcome several issues. The variety of hybridization partners lets improving artemisinin bioactivity by tuning the ability of hybrids to interact with various molecule targets involved in multiple biological pathways. The review highlights the current scenario of artemisinin-derived hybrids with potential anticancer activity with the aim to facilitate further rational design of more effective candidates.

Pioneering Precision in RNA Therapeutics" – Thazha P. Prakash‏‏‏  ‏ Executive Research of Medicinal Chemistry at Ionis Pharmaceuticals, is a globally recognized leader in RNA-based drug development. As the co-inventor of ligand-conjugated antisense (LICA) technology, his work has enabled tissue-specific targeting, with over 10 LICA ASO drugs in clinical trials. He has developed key chemical innovations, including cEt BNA for ASOs and modified RNAs for siRNAs and CRISPR/Cas9. With over 230 publications and patents, Dr. Prakash's contributions continue to transform the field of precision medicine. #NucleicAcidTherapeutics #OTSIndia2025 #BiotechnologyInnovation #MolecularBiologyResearch #GeneticEngineering #PharmacologyAdvances #Bioinformatics #BiochemistryBreakthroughs #TherapeuticsConference #ScientificMeeting #HealthcareInnovation #BengaluruEvents #India2025 #OligonucleotideTherapies #LifeSciencesResearch

Oligonucleotide therapeutics have recently seen significant developments in drug development, yet bioanalytical challenges—like chromatographic retention, stability, and complex extractions—persist. At KCAS Bio, we’ve built robust strategies to overcome these obstacles: 🔹 Chromatographic Precision: Our optimized IP-RP chromatography ensures high resolution and response, fine-tuned with select ion-pair reagents. 🔹 Optimized Extraction Techniques: Tailored approaches, including mixed-mode SPE, provide precise quantitation in challenging matrices. Read our blog to discover more about how KCAS Bio is leading oligonucleotide quantitation and bringing new possibilities to life. https://lnkd.in/gCydCxaw #Biotech #Oligonucleotides #DrugDevelopment #KCASBio

~60% drug approvals in the past decade are small molecules. Novel small molecule drugs, such as molecular glues and proteolysis-targeting chimeras (PROTACs), are growing into the latest weapons to help humanity defeat certain diseases. The continuous application of artificial intelligence will also directly promote the design and development of small molecule drugs. There are many challenges for small molecule drug discovery and development, e.g., low molecular weight, low solubility, time-consuming process and non-specific binding. Label-free binding technologies have been widely used for small molecule kinetic analysis. I’ve seen more and more successful stories these days that BLI platform serve as an invaluable tool in addition to SPR. Especially small molecules immobilized as ligands for target screening. However, Gator Bio NextGen BLI extended this application further with it’s unique SMAP probe (Zewen Wen, Chengchun Chen，et al. Baohuoside I inhibits virulence of multidrug-resistant Staphylococcus aureus by targeting the transcription Staphylococcus accessory regulator factor SarZ. Phytomedicine. 2024). The innovation is not just on the probe at Gator Bio, the Gator® Pivot instrument is designed for intermediate-throughput analysis. 16 spectrometers enable high frequency parallel measurement of up to 16 samples. It is also equipped with temperature and evaporation control that alleviates concerns about analyzing thermally unstable proteins and the risk of sample evaporation during extended runs.  For quick quantitation, 816 samples can be analyzed in one setup. I believe Gator® Pivot is the best value and most cost-effective BLI instrument on the market today. #BLI #SPR #SmallMoleculeDrug #SMAP #GatorPivot

🧬 The free-state behavior of compounds in solution can have significant impact on the entire drug discovery process since it is one of the main sources of artifacts in assays. ✔ At NMX, we harness the versatility of NMR to evaluate solubility and aggregation of your molecules. ✔ We are a leader in the study and characterization of free-state behavior using biophysics. 👉 Want to learn more? Contact us to become a CRP (Contract Research Partner) with us and see how we can surpass your expectations of a traditional CRO. Email: nmx@nmxresearch.com now. More information about our services here: https://lnkd.in/g4FN_5bd #CRP #PRC #partenaire #recherche #contractuelle #contract #research #partner #ORC #CRO #biopharma #biophysics #pharma #pharmaceutical #drugdiscovery #medicament #innovation #specialization #FBDD

Happy to share that our Special Issue entitled "In Silico and In Vitro Screening of Small Molecule Inhibitors" has been launched by Pharmaceuticals. This Special Issue aims to highlight the latest advances, challenges, and applications of in silico tools and in vitro screening in the field of drug discovery for SMIs. We welcome the submission of research and review articles on advances in drug discovery, design, and development of biological target inhibitors against various disease models. Scientists from both academia and industry are invited to submit their manuscripts covering relevant topics, including the design and synthesis of novel chemical entities (NCEs), repurposing of approved drugs, cell-based or animal experiments, and in silico computational approaches to elucidate future directions in drug discovery. Guest Editors Dr Usama Ammar (Edinburgh Napier University, United Kingdom) Dr Domiziana Masci (Catholic University of the Sacred Heart, Italy) Submission Deadline: 5 November 2024 For more information please visit our website https://lnkd.in/e3bGFpHU https://lnkd.in/esVCnjPV #Pharmaceuticals #Special_Issue #Medicinal_Chemistry #Small_Molecule_Inhibitors