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A recent work from the University of Perugia (Italy) investigates the 𝗽𝗿𝗲𝗱𝗶𝗰𝘁𝗶𝗼𝗻 𝗼𝗳 𝗹𝗶𝗽𝗼𝗽𝗵𝗶𝗹𝗶𝗰𝗶𝘁𝘆 𝗮𝗻𝗱 𝘀𝗼𝗹𝘂𝗯𝗶𝗹𝗶𝘁𝘆 𝗳𝗼𝗿 𝗣𝗥𝗢𝗧𝗔𝗖𝘀.  PROTACs falls into a Bro5 space and display general poor solubility/permeability because of high MW, high logD and TPSA. Many nanoformulation strategies tackled the PROTACs poor bioavailability in the preclinical phase, to facilitate the transport target-protein degraders to the disease site. However, PROTACs low solubility affects early drug discovery bioassays by causing underestimated bioactivity, variable data an inaccurate SAR.  The efficient prediction of solubility would then generate a more accurate SAR, in-vivo profile and reduce formulation in late-stage drug development.  𝗞𝗶𝗻𝗲𝘁𝗶𝗰 𝘀𝗼𝗹𝘂𝗯𝗶𝗹𝗶𝘁𝘆 𝗮𝗻𝗱 𝗟𝗼𝗴𝗗 𝗽𝗛=𝟳.𝟰 𝘄𝗲𝗿𝗲 𝗲𝘅𝗽𝗲𝗿𝗶𝗺𝗲𝗻𝘁𝗮𝗹𝗹𝘆 𝗰𝗮𝗹𝗰𝘂𝗹𝗮𝘁𝗲𝗱 𝗳𝗼𝗿 𝗮 𝗱𝗮𝘁𝗮𝘀𝗲𝘁 𝗼𝗳 𝟰𝟰 𝗣𝗥𝗢𝗧𝗔𝗖𝘀 𝘄𝗶𝘁𝗵 𝗱𝗶𝗳𝗳𝗲𝗿𝗲𝗻𝘁 𝘂𝗻𝗶𝘁𝘀 (𝟵 𝗣𝗢𝗜 𝗹𝗶𝗴𝗮𝗻𝗱𝘀, 𝟳 𝗹𝗶𝗻𝗸𝗲𝗿𝘀 𝗮𝗻𝗱 𝟱 𝗘𝟯 𝗹𝗶𝗴𝗮𝘀𝗲 𝗹𝗶𝗴𝗮𝗻𝗱𝘀) 𝗮𝗻𝗱 𝘃𝗮𝗿𝗶𝗮𝗯𝗹𝗲 𝗽𝗵𝘆𝘀𝗶𝗰𝗼𝗰𝗵𝗲𝗺𝗶𝗰𝗮𝗹 𝘀𝗽𝗮𝗰𝗲 (𝗠𝗪, 𝗛𝗕𝗗, 𝗛𝗕𝗔, 𝗙𝗹𝗲𝘅, 𝗰𝗟𝗼𝗴𝗣). Detection was performed with UV-Vis and UPLC-MS with good correlation, although LC-MS allows a lower limit of detection (LOD), therefore more suitable for low-solubility PROTACs.  Additionally, the experimental analysis of solubility/lipophilicity for matched pair PROTACs provides useful indications for linker units (bases, PEGs, heteroaromatic) and ligands for E3 ligase that improve PROTAC solubility.  Experimental values were then compared to predicted n-octanol/buffer pH 7.4 distribution coefficients (logD7.4) with several in-silico predictors, showing a larger standard deviation with respect to smaller molecules falling into the Lipinski Ro5 space.  The authors then generated a 𝗽𝗿𝗲𝗱𝗶𝗰𝘁𝗶𝘃𝗲 𝗺𝗼𝗱𝗲𝗹𝘀 𝗳𝗼𝗿 𝗟𝗼𝗴𝗗𝟳.𝟰 𝗮𝗻𝗱 𝗸𝗶𝗻𝗲𝘁𝗶𝗰 𝘀𝗼𝗹𝘂𝗯𝗶𝗹𝗶𝘁𝘆 𝗱𝗮𝘁𝗮 𝘁𝗵𝗿𝗼𝘂𝗴𝗵 𝗽𝗮𝗿𝘁𝗶𝗮𝗹 𝗹𝗲𝗮𝘀𝘁 𝘀𝗾𝘂𝗮𝗿𝗲𝘀 (𝗣𝗟𝗦) 𝗿𝗲𝗴𝗿𝗲𝘀𝘀𝗶𝗼𝗻 𝗺𝗲𝘁𝗵𝗼𝗱. A dataset of 36 PROTACs with experimental Ksol and LogD was modelled in the most abundant ionization state and considering that PROTACs display more likely and elongated and polar conformations in aqueous media, whereas aprotic solvents favour a folded conformation to minimize the exposure of polar groups. The recalculated vs experimental data plot for logD and Ksol showed good correlation and demonstrated that classical physicochemical descriptors together with protonation state prediction proved very efficient to model those PROTACs' physicochemical properties. https://lnkd.in/edCK3UF5

Have you considered how drug repurposing effectively targets diseases at the molecular level and how computational tools deliver rapid, cost-effective solutions for global health emergencies? I recently participated in a well-designed Skill Development Program on Drug Discovery and Molecular Docking, organized by #Biopractify and #Swastome (06.01.2025-12.01.2025). Here are the key insights developed during weeklong sessions: Day 1 and 2: In-Silico Molecular Docking-Based Drug Repurposing Drug repurposing is a revolutionary approach to identifying new therapeutic uses for existing, FDA-approved drugs. This process significantly accelerates development time, reducing it from the typical 10 to 18 years to an impressive 3 to 12 years. Molecular Docking Process: 1.     Preparation: Acquire and refine 3D structures of drugs and proteins with precision. 2.     Docking: Harness AutoDock Vina's power to conduct docking, confidently selecting the configurations with the lowest binding energy. 3.     Post-Docking: Calculate binding energy and thoroughly evaluate ligand-protein interactions. Key Tools: UniProt, PubChem, ZINC, PyRx, PLIP, ADMET Lab 3.0, Vina Split, and Procheck. Day 3 and 4: Navigating the Pharmaceutical Regulatory Landscape 1.     Drug Development: Explored various aspects of the drug discovery process, from preclinical research to securing regulatory approval. 2.     Regulatory Framework: Dissected the roles of FDA and EMA, mastering the important ICH guidelines that govern drug safety and efficacy. 3.     Preclinical Development: Tackled objectives, navigated the regulatory landscape, and prepared for the critical transition to clinical trials. 4.     Challenges: Identified the significant scientific, regulatory, and ethical challenges. Day 5-7: Protein Structure Modelling and Molecular Dynamics (MD) Simulation 1. Protein Structure Modelling: o   Developed understanding of various structural modelling techniques (SWISS-MODEL, MODELLER, AlphaFold, etc.) o   Conducted homology modelling with precision and rigorously assessed model quality using the DOPE score and GA341 score. o   Utilized Modeller, Gnuplot, Matplotlib, and Procheck for molecular dynamics simulations. 2. MD Simulation: o   Developed a keen understanding of atom positioning in biomolecular systems and the intricate forces at play among them. o   Explored a range of force fields, including AMBER, Drude oscillator model, AMOEBA, COMB, etc. o   Effectively utilized Galaxy Australia for impactful MD simulations. 3. MD Simulation Steps: o   Set up topology for proteins and ligands with accuracy, created simulation boxes, added solvent and ions, and minimized energy with confidence. Conducted in-depth analyses and production simulations, including RMSD/RMSF and PCA analyses. I'd like to thank Team #Biopractify and #Swastome for conducting such skill-oriented programs. #Drug Discovery #Molecular Docking #Regulatory #Molecular Dynamics Simulation #late post 😊 😊 😊

Combining cheminformatics with molecular docking offers several benefits for accelerating drug discovery: #Enhanced Virtual Screening: Cheminformatics can handle vast chemical libraries to identify potential drug candidates. Molecular docking can then predict how these candidates bind to target proteins, refining the selection process and increasing the efficiency of finding promising leads. #Improved Accuracy: Cheminformatics provides detailed chemical property analysis, while molecular docking offers insights into molecular interactions. Together, they enhance the accuracy of predicting the efficacy of drug candidates. #Cost and Time Efficiency: This combination allows for the prioritization of compounds before costly and time-consuming experimental procedures. Virtual screening and docking reduce the need for extensive laboratory testing by filtering out less promising candidates early on. #Better Understanding of Mechanisms: Cheminformatics data can reveal the structural properties of molecules, while molecular docking can elucidate binding mechanisms. This integrated approach offers a comprehensive understanding of how potential drugs interact with their targets. #Facilitates Lead Optimization: By providing insights into the structural and interaction profiles of compounds, cheminformatics and molecular docking help in optimizing lead compounds, and improving their potency, selectivity, and pharmacokinetic properties. #Supports Structure-Based Drug Design: The combination aids in designing new molecules based on the structure of the target protein. Cheminformatics can suggest modifications and molecular docking can validate their impact on binding affinity and specificity. #Data Integration and Management: Cheminformatics tools can manage and integrate large datasets from various sources, providing a solid foundation for molecular docking studies. This streamlined data handling accelerates the drug discovery process. #Predicting Drug Resistance and Side Effects: Cheminformatics can predict potential off-target effects and drug resistance mechanisms. Molecular docking can validate these predictions by simulating interactions with multiple targets, aiding in designing safer and more effective drugs. If you plan to advance your skills and make your research projects adopt cutting-edge technologies for accelerating drug discovery saving time and reducing cost, come and join our upcoming workshop which will be led by a prominent professor, Shaymaa Emam Kassab who rocked in the field with several prestigious publications: https://lnkd.in/dyEEePav https://lnkd.in/dGkZ2j4j https://lnkd.in/diVfrX_q https://lnkd.in/dee5JrUX https://lnkd.in/dtW6VyQH Registration link: https://lnkd.in/dPfh7GEJ

[𝗪𝗼𝗿𝗸𝘀𝗵𝗼𝗽𝘀] Philly Area, Oct 9 - We’ll be conducting free hands-on drug design workshops at the Sheraton Valley Forge, King Of Prussia. The morning session will focus on Biologics: Protein Alignments, Modeling and Docking, while the afternoon will cover Small Molecule Docking and Fragment-based Design (see agenda below). This event is open to everyone, regardless of prior software experience. For course descriptions and to registration, please visit: https://bit.ly/3StDL7j AGENDA 09:00-12:00 𝗕𝗶𝗼𝗹𝗼𝗴𝗶𝗰𝘀: 𝗣𝗿𝗼𝘁𝗲𝗶𝗻 𝗔𝗹𝗶𝗴𝗻𝗺𝗲𝗻𝘁𝘀, 𝗠𝗼𝗱𝗲𝗹𝗶𝗻𝗴 𝗮𝗻𝗱 𝗗𝗼𝗰𝗸𝗶𝗻𝗴 This workshop covers essential methods for aligning protein sequences, superposing structures, loop modeling, building fusion protein models, and conducting protein-protein docking. Participants will learn techniques for grafting and refining antibody CDR loops, as well as using a knowledge-based approach to scFv fusion protein modeling with the Linker Modeler application. The session will also cover protein-protein docking of an antibody to an antigen and epitope mapping. Finally, the workshop will guide participants through a complete workflow for generating a QSAR model to predict and analyze protein/biologics solubility. 13:00-15:00 𝗦𝗺𝗮𝗹𝗹 𝗠𝗼𝗹𝗲𝗰𝘂𝗹𝗲 𝗗𝗼𝗰𝗸𝗶𝗻𝗴 This workshop will explore some variants of protein-ligand docking to predict the binding of small-molecule structures to a protein target. Pharmacophore-guided docking will be used to preserve key interactions, whereas template-based docking will efficiently position congeneric series of compounds in the binding site. Reaction-based covalent docking will generate poses for covalently bound ligands. Analysis of docking results and techniques to achieve high-throughput docking will also be addressed. 15:00-15:30 𝗕𝗿𝗲𝗮𝗸   15:30-17:00 𝗙𝗿𝗮𝗴𝗺𝗲𝗻𝘁-𝗕𝗮𝘀𝗲𝗱 𝗗𝗲𝘀𝗶𝗴𝗻: 𝗦𝗰𝗮𝗳𝗳𝗼𝗹𝗱 𝗛𝗼𝗽𝗽𝗶𝗻𝗴, 𝗙𝗿𝗮𝗴𝗺𝗲𝗻𝘁 𝗚𝗿𝗼𝘄𝗶𝗻𝗴 𝗮𝗻𝗱 𝗕𝗶𝗼𝗶𝘀𝗼𝘀𝘁𝗲𝗿𝗶𝗰 𝗥𝗲𝗽𝗹𝗮𝗰𝗲𝗺𝗲𝗻𝘁𝘀 This workshop will focus on applications for fragment-based drug design, covering methods such as scaffold hopping, fragment growing and R-group exploration to generate novel compound ideas, then optimize and score the structures in the pocket. The use of molecular descriptors and pharmacophore models to guide these computational methods will also be discussed. In addition, an SBDD method for generating closely related analogs through bioisosteric replacements will be presented. 17:00-18:00 𝗦𝗼𝗰𝗶𝗮𝗹 𝗛𝗼𝘂𝗿 - - - 𝗩𝗲𝗻𝘂𝗲: Sheraton Valley Forge 480 North Gulph Road, King Of Prussia, PA 19406 #DrugDesign #DrugDiscovery #CADD #SBDD #CompChem #MedChem #Biologics

Our latest blog delves into how qPCR technology is transforming the bioanalysis of oligonucleotide drugs. Find out why qPCR is becoming the preferred method for analyzing these drugs due to its superior sensitivity, faster development times and higher throughput. This article also covers the classification and mechanism of action of various oligonucleotide drugs, making it a must-read for anyone in the field of biomedical research. #OligonucleotideBioanalysis #qPCRAdvancements #BiotechInnovation #DrugDevelopment #MolecularBiology https://hubs.li/Q02z-s9R0

Our latest blog delves into how qPCR technology is transforming the bioanalysis of oligonucleotide drugs. Find out why qPCR is becoming the preferred method for analyzing these drugs due to its superior sensitivity, faster development times and higher throughput. This article also covers the classification and mechanism of action of various oligonucleotide drugs, making it a must-read for anyone in the field of biomedical research. #OligonucleotideBioanalysis #qPCRAdvancements #BiotechInnovation #DrugDevelopment #MolecularBiology https://hubs.li/Q02z-wdB0

#RecommendedPaper 🧫Gut-on-a-Chip Research for Drug Development: Implications of Chip Design on Preclinical Oral Bioavailability or Intestinal Disease Studies by Joanne M. Donkers, et al. 🔎Read the full paper here: https://lnkd.in/dG_CVzjS #organ #chip #microbiome

Join Curia at #SLAS2025 in San Diego, January 25-29. Stop by Booth #319 to meet our small molecule discovery experts and discuss how Curia can accelerate your discovery program with our best-in-class capabilities in medicinal chemistry, in vitro pharmacology, and structural biology. Don’t miss the poster session on 1/27 from 12 PM to 1 PM, where Curia will present: Evaluating Efficacy of Large Molecule Therapeutics Using a Multiparametric High-Content Imaging Approach (Poster: 1184-A) with insights from our expert Jennifer Gasparek, Senior Research Scientist, Cell Biology at Curia. Looking for a partner with proven expertise in high-throughput lead discovery and development for small and large molecules? Discover how we’re transforming the evaluation of small molecule compounds, therapeutic antibodies, and biologics. From #CuriosityToCure, let’s collaborate and unlock new possibilities together. Schedule a meeting with our expert!: https://ow.ly/6f7E50UJECJ #SLAS2025 #Biologics #HighThroughputDiscovery #smallmolecules #therapeuticantibodies

A Complete Guide to “ 𝐂𝐞𝐥𝐥 𝐂𝐮𝐥𝐭𝐮𝐫𝐞” [PDF-Guide] ➤ 𝐂𝐥𝐢𝐜𝐤 𝐡𝐞𝐫𝐞 𝐭𝐨 𝐆𝐞𝐭 𝐏𝐃𝐅: https://lnkd.in/gZnBs89x The #cellculture market comprises various consumables and equipment required at different stages of the cell culture technique to understand the basic #biology and #biochemistry of cells. It acts as a model system and can be used for various applications such as #bioproduction, cancer research, stem cell research, diagnostics, and drug screening. Major #pharmaceutical and #biotech companies collaborated to find #vaccines and treatment methods during the pandemic. The idea behind the collaboration was to come together and find a solution as quickly as possible during the pandemic, which could not be possible alone. Collaborations also took place within companies and universities to speed up the #research and production process. Outsourcing pharmaceutical and #biotechnological research to contract research organizations (CROs) also increased during the pandemic. ➤ 𝐃𝐫𝐢𝐯𝐞𝐫𝐬  1. Rising Demand for #Biopharmaceuticals 2. Strong R&D Pipeline for Biopharmaceuticals 3. Government Initiatives to Promote Biosimilars 4. Capacity Expansions of #BiopharmaceuticalPlants ➤ 𝑲𝒆𝒚 𝑷𝒍𝒂𝒚𝒆𝒓𝒔: Merck KGaA (Germany), Thermo Fisher Scientific Inc. (U.S.), Cytiva (U.S.), Lonza Group Ltd. (Switzerland), Corning Incorporated (U.S.), Becton, Dickinson and Company (U.S.), Avantor, Inc. (U.S.), Bio-Rad Laboratories, Inc.  #CellBiology #TissueCulture #LabLife #CellResearch #CellScience #CellGrowth #InVitro #Biotech #StemCells #Microbiology #BioResearch #LifeSciences #Biomedical #CellTech #LabTechniques #ScienceResearch #MolecularBiology #ResearchLab

A Complete Guide to “ 𝐂𝐞𝐥𝐥 𝐂𝐮𝐥𝐭𝐮𝐫𝐞” [PDF-Guide] ➤ 𝐂𝐥𝐢𝐜𝐤 𝐡𝐞𝐫𝐞 𝐭𝐨 𝐆𝐞𝐭 𝐏𝐃𝐅: https://lnkd.in/gZnBs89x The #cellculture market comprises various consumables and equipment required at different stages of the cell culture technique to understand the basic #biology and #biochemistry of cells. It acts as a model system and can be used for various applications such as #bioproduction, cancer research, stem cell research, diagnostics, and drug screening. Major #pharmaceutical and #biotech companies collaborated to find #vaccines and treatment methods during the pandemic. The idea behind the collaboration was to come together and find a solution as quickly as possible during the pandemic, which could not be possible alone. Collaborations also took place within companies and universities to speed up the #research and production process. Outsourcing pharmaceutical and #biotechnological research to contract research organizations (CROs) also increased during the pandemic. ➤ 𝐃𝐫𝐢𝐯𝐞𝐫𝐬  1. Rising Demand for #Biopharmaceuticals 2. Strong R&D Pipeline for Biopharmaceuticals 3. Government Initiatives to Promote Biosimilars 4. Capacity Expansions of #BiopharmaceuticalPlants ➤ 𝑲𝒆𝒚 𝑷𝒍𝒂𝒚𝒆𝒓𝒔: Merck KGaA (Germany), Thermo Fisher Scientific Inc. (U.S.), Cytiva (U.S.), Lonza Group Ltd. (Switzerland), Corning Incorporated (U.S.), Becton, Dickinson and Company (U.S.), Avantor, Inc. (U.S.), Bio-Rad Laboratories, Inc.  #CellBiology #TissueCulture #LabLife #CellResearch #CellScience #CellGrowth #InVitro #Biotech #StemCells #Microbiology #BioResearch #LifeSciences #Biomedical #CellTech #LabTechniques #ScienceResearch #MolecularBiology #ResearchLab