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Matt Strempel, the grand-prize winner of the 93rd Annual WD Writing Competition, shares his insights on incorporating humor into writing and the value of having a trusted mentor. Strempel's interest in writing began while collaborating with his grandmother, and he now uses his train commutes for dedicated writing time. His winning entry, "Botched," is a humorous short story about anniversary gifts gone wrong. Strempel draws inspiration from writers like David Sedaris and George Saunders, who skillfully balance humor and substance. He advises aspiring writers to find a mentor and seek feedback to improve their craft. The text also provides a list of books and authors in various genres, including humor, inspiration/spiritual, mainstream/literary short story, memoir/personal essay, nonfiction essay or article, non-rhyming poetry, and rhyming poetry, with brief information about the authors and their achievements. [Extracted from the article]

Dr. Liz O'Riordan, a former consultant breast surgeon, shares her personal journey from being a doctor who delivered cancer diagnoses to becoming a cancer patient herself. She discusses the emotional toll of breaking bad news and the unhelpful phrases used by clinicians. Dr. O'Riordan recounts her own experience with breast cancer, including chemotherapy, mastectomy, and the impact on her mental health and body image. She emphasizes the importance of exercise, finding joy in small things, and seeking support during the cancer journey. Dr. O'Riordan also highlights recent advancements in breast cancer research and encourages regular breast checks and mammograms for early detection. [Extracted from the article]

The article discusses the role of DNA or RNA molecules arranged into spherical shapes in treatment of brain cancer. Topics include anticancer drugs, selecting a specific sequence of DNA made of A, T, C and G nucleotides, transcribe that sequence into a form called messenger RNA, and disease treatments by screening hundreds of thousands of small synthetic or natural molecules.

The article discusses that the first respiratory syncytial virus (RSV) vaccination for elderly people has been given Food and Drug Administration approval; and mentions risk of acquiring severe RSV infections is higher in those older than 65 with chronic lung disease and impaired immune systems.

A recent article in Drug Week discusses the development of novel flavonoid senolytics, SR29384 and SR31133, which have shown enhanced senolytic activities in eliminating senescent cells and reducing tissue senescence in vivo. These compounds were developed through a senescent cell-based phenotypic drug discovery approach that combines drug screening and drug design. Mechanistic studies suggest that these senolytics target specific proteins to induce selective senescent cell death, offering potential clinical applications in treating aging and age-related diseases. The preprint has not yet been peer-reviewed, but represents a significant advancement in the field of drug development for age-related conditions. [Extracted from the article]

The article discusses the challenges in targeting undruggable proteins and introduces Uni-Clip, a contrastive learning framework that enhances the modeling of protein-ligand interactions. Uni-Clip shows superior performance in benchmark evaluations and proves to be a practical tool for drug discovery applications. The framework successfully identified non-covalent inhibitors for the challenging protein target GPX4 and highlighted potential repurposing of benzbromarone in cancer therapy. The preprint has not been peer-reviewed and more information can be found on biorxiv.org. [Extracted from the article]

Researchers at the School of Pharmaceutical Science and Technology in Hangzhou, China, have conducted a study on the development of novel PDE4B inhibitors for dampening inflammatory responses in immune and inflammatory cells. The study utilized computer-aided drug design, synthesis, and activity evaluation to optimize a compound, MR9-302, which showed enhanced inhibitory activity compared to the original compound, MR9. This research, supported by various funding sources, has been peer-reviewed and published in Tetrahedron. For more information, readers can contact the lead author, Zhili Zuo, at the School of Pharmaceutical Science and Technology in Hangzhou. [Extracted from the article]

University of Belgrade researchers have developed novel ROCK inhibitors through computer-aided drug design to target the actin cytoskeleton in cancer cells. The study focused on ROCK1 and ROCK2 inhibitors, showing promising results in inhibiting cancer cell growth and metastasis. The researchers suggest a multi-target approach for future cancer therapies, emphasizing the potential of ROCK inhibitors in improving therapeutic efficacy in metastatic tumors. [Extracted from the article]

A recent study conducted at the Izmir Biomedicine and Genome Center focused on Acute Myeloid Leukemia (AML) and the challenges of single-target drug therapies due to network rewiring. The researchers proposed a multi-targeting approach to inhibit the AML network, utilizing computer-aided design to identify potential drug combinations and de novo agents. By integrating network and structural pharmacology, the study identified strategies for precision medicine in AML treatment, emphasizing the importance of preclinical and clinical testing. For more information, the full article is available in Cancers journal. [Extracted from the article]

The article discusses the role of scientific research in the selection of drug candidates for clinical development by pharmaceutical firms. It highlights the importance of in-house scientific research in increasing the likelihood of drug development success. The research emphasizes the need for a 'rational drug design' approach that is grounded in scientific research. The study was conducted by researchers at Hasselt University in Belgium and was supported by FWO. [Extracted from the article]

The article discusses the use of artificial intelligence in drug discovery, specifically focusing on structure-based drug design (SBDD) using two methodologies called Rag2Mol-G and Rag2Mol-R. These methods utilize retrieval-augmented generation (RAG) to design small molecules that fit into a 3D pocket, resulting in drug candidates with superior binding affinities and drug-likeness. The research highlights the potential of these methods in identifying promising inhibitors for challenging targets, such as PTPN2, and offers a highly extensible framework for integrating diverse SBDD methods. The preprint has not been peer-reviewed, and more information can be found on biorxiv.org. [Extracted from the article]

Researchers at Madras Christian College in Tamil Nadu, India, have conducted a study on N-tert-Butoxy carbonyl imidazole, focusing on computational techniques and experimental assays to analyze its potential in drug design. The study included in vitro cytotoxicity activity testing and found that the compound shows promise in treating cervical cancer and is non-toxic. The research, supported by King Saud University, has been peer-reviewed and published in the Journal of the Indian Chemical Society. For more information, readers can contact the lead author at Madras Christian College. [Extracted from the article]

Research from Lomonosov Moscow State University delves into Staphylococcus aureus, highlighting Sortase A as a key target for antibacterial development. The study focuses on using ensemble docking to design peptidomimetic inhibitors for SrtA, aiming to reduce antimicrobial resistance. The research offers a new approach for rational drug design and provides insights for future synthesis and testing of potential inhibitors. [Extracted from the article]

A recent study from Poornima University in Rajasthan, India, explores the role of water molecules in CT-DNA interactions and its implications for drug design. The research highlights how water-mediated interactions with DNA impact drug-DNA binding kinetics and thermodynamics, influencing drug efficacy. By leveraging insights into water-DNA interactions, researchers aim to enhance drug potency, selectivity, and resistance profiles in the rational design of DNA-targeting drugs. This peer-reviewed study utilizes experimental and computational methods to unravel the complex dynamics of water molecules in DNA hydration shells. [Extracted from the article]

A study conducted at the University of California San Francisco (UCSF) explored the use of AlphaFold2 (AF2) models for ligand discovery in the sigma(2) and serotonin 2A (5-HT2A) receptors. The research found that docking against AF2 models yielded high hit rates and affinities comparable to experimental structures, despite differences in residue conformations. The study suggests that AF2 models, while sampling different conformations from experimental structures, are still relevant for ligand discovery, expanding the scope of structure-based drug design. This peer-reviewed research provides valuable insights into the potential of AF2 structures in guiding prospective ligand discovery. [Extracted from the article]

A recent study from the University of KwaZulu-Natal in Durban, South Africa, explores the development of new anti-tuberculosis agents to combat drug-resistant strains of tuberculosis. Researchers are investigating the molecular hybridization technique to create new compounds based on isoniazid, a front-line anti-TB drug. The study aims to address the challenges posed by drug-resistant tuberculosis and provide potential leads for further research and development. [Extracted from the article]

Researchers from Huazhong University of Science and Technology in Wuhan, China, have conducted a study on Proteolysis Targeting Chimera (PROTAC) technology in biomedicine and pharmacotherapy. The study highlights the efficacy of small molecule PROTACs in degrading disease-specific proteins and explores new technologies to overcome limitations. The research aims to provide insights for future advancements in targeting chimera design. For more information, the full article can be accessed through the publisher Elsevier. [Extracted from the article]

University of Dundee scientists have developed a novel "cut and sew" process to accelerate drug design, particularly for diseases like cancer. This innovative method involves custom-building a new version of a protein commonly targeted by "protein degraders," which removes unwanted parts of the protein before stitching the remaining parts together. The research tool created through this process, known as "CRBN-midi," has been made widely available to the scientific community to aid in drug discovery efforts. This breakthrough is expected to advance the development of new degrader drugs that target disease-causing proteins, ultimately benefiting patients facing significant health challenges. [Extracted from the article]

Roche Holding AG's experimental Alzheimer's treatment resulted in the death of an elderly patient, leading to trial design changes. Despite this, overall results support further testing, with the drug showing promise in clearing toxic proteins associated with the disease. The drug, trontinemab, demonstrated lower rates of brain swelling or bleeding compared to similar treatments, prompting optimism for its potential in the crowded anti-amyloid space. Roche plans to continue testing the drug in the second stage of the Phase 1 study to assess its long-term effects and dosing regimens. [Extracted from the article]

A recent study conducted at the University of Copenhagen focused on the development of Polar Bodipy-tetrazines for rapid pretargeted fluorescence imaging in the field of Chemicals and Chemistry. The research demonstrated successful in vivo binding of the tetrazine dyes to a preaccumulated monoclonal antibody, showing promising results for potential cancer treatments like photodynamic or -thermal therapy. The study highlighted the potential of using turn-on probes for cancer treatments, with high tumor-to-muscle ratios observed in fluorescence imaging. For more information, readers can refer to the original article published in ACS Omega. [Extracted from the article]

Research from the University of Bayreuth in Germany explores the immunomodulatory properties of HDAC6 inhibitors in cancer treatment. HDAC6 inhibitors show promise in designing anticancer drugs that interact with the immune system, potentially improving therapy options for cancer patients. This peer-reviewed study highlights the development of new HDAC6 inhibitors with immunomodulatory activities for sophisticated drug design and treatment optimization in cancer diseases. [Extracted from the article]

Researchers from the University of Naples "Federico II" have conducted a study on the use of metal-antimicrobial peptides to combat drug-resistant bacteria and fungi. The study highlights the potential of antimicrobial peptides (AMPs) in fighting antimicrobial resistance, with a focus on the effects of divalent metal ions on peptide activity. The research explores how metal ions can alter the structure of AMPs to enhance their effectiveness against bacteria. This study provides valuable insights into potential strategies for developing new antimicrobial treatments. [Extracted from the article]

Researchers from the Department of Bioengineering in Agartala, India, have developed a machine-learning framework called Lgbm-acp to predict and screen anticancer peptides with potential drug targets. The model demonstrated high accuracy and outperformed existing computational tools, identifying a promising peptide with strong binding affinity to multiple anticancer drug targets. This study aims to advance rational drug design by facilitating the rapid identification and screening of therapeutic peptides. The research was supported by NIT Agartala and has been peer-reviewed, offering valuable insights into alternative approaches for cancer therapy. [Extracted from the article]

The article discusses the development of non-muscle myosin II (NMII) small molecule inhibitors with broad therapeutic potential. These inhibitors selectively target NMII over cardiac myosin II (CMII), showing promise in preclinical models of stimulant use disorder. The research aims to provide new disease treatments and valuable tools for the scientific community, offering potential leads for future medication development. The preprint has not yet undergone peer review. [Extracted from the article]

Research from Oregon Health & Science University (OHSU) has provided new insights into the structure and function of the human P2X1 receptor, a trimeric cation channel activated by ATP. The study utilized cryo-EM structures to reveal subtype-specific architecture and the antagonistic effects of supramolecular ligand-binding, shedding light on the molecular pharmacology of the receptor and potentially informing future drug design efforts. Funders for this research included the U.S. Department of Health & Human Services, the National Heart, Lung, and Blood Institute, and the American Heart Association. [Extracted from the article]

Researchers from the Department of Mathematics in Sialkot, Pakistan, have developed a quadratic regression model to analyze the topological characteristics of several antiviral drugs, including favipiravir, baricitinib, fluvoxamine, nirmatrelvir, molnupiravir, lopinavir, and remdesivir. The study aimed to determine the physicochemical properties of these drugs and their potential effectiveness in treating COVID-19. The results showed a significant correlation between the investigated topological coindices and the physicochemical properties of the drugs. This research has been peer-reviewed and published in The Journal of Supercomputing. [Extracted from the article]

A preprint abstract from biorxiv.org discusses the development of FragLlama, a large language model trained for molecular design. FragLlama uses custom tokens to represent molecular fragments and functional groups, and it is designed to generate molecules given one or two fragments. The model has been applied to various drug design scenarios, such as hit-to-lead and lead optimization stage drug design, PROTAC linker design, and mapping to commonly used drug design strategies. FragLlama has shown proficiency in reproducing expert-level designs and exploring novel chemical spaces, potentially enhancing the capabilities of medicinal chemists in drug design. Please note that this preprint has not undergone peer review. [Extracted from the article]

A recent study conducted by researchers at the University of Cagliari in Italy focused on indicators and reagents in the field of radiopharmaceuticals. Radiopharmaceuticals are important tools in cancer diagnosis and therapy, and metal-based radiopharmaceuticals consist of a radiometal-chelator complex linked to a bio-vector that targets specific tumors. The researchers investigated various radiometal-chelator complexes using quantum mechanics methods and molecular dynamics simulations. The study provides valuable insights into the properties of these complexes and offers potential applications in predictive models, molecular modeling, and rational drug design. [Extracted from the article]

Researchers at Jagiellonian University in Krakow, Poland have developed an Android application called MedChem Game that uses gamification and artificial intelligence to help users learn about medicinal chemistry and design new small-molecule drugs. The application includes a simplified molecule drawing tool and a 3D ligand-protein viewer, allowing users to propose new drug candidates and inspect molecular docking results. The system also incorporates a continuously trained deep generative model that learns from user-developed compounds to improve the quality of generated molecules. The researchers suggest that MedChem Game could be a useful supplement to courses on small-molecule drug design. [Extracted from the article]

A recent preprint abstract discusses the structural basis for immune cell binding of Fusobacterium nucleatum, a bacteria commonly found in the human oral cavity. This bacteria is often overrepresented in the colon microbiota of colorectal cancer patients and has been linked to tumor chemoresistance, metastasis, and a poor therapeutic prognosis. The study focuses on a specific adhesin called CbpF, which targets a protein called CEACAM1 on T-cells and is associated with immune evasion of Fusobacterium-colonized tumors. The researchers used cryogenic electron microscopy and single particle analysis to obtain high-resolution structures of CbpF alone and in complex with CEACAM1, providing new insights into the binding mechanism. This research could potentially lead to the development of targeted drugs for colorectal cancer. [Extracted from the article]

Circle's platform uses structure-based rational drug design and synthetic chemistry to discover cell-permeable macrocycles. [ABSTRACT FROM AUTHOR]

A preprint abstract from biorxiv.org discusses the use of computational methods in drug design to generate molecules. Traditional methods are costly and time-consuming, so researchers have turned to diffusion models for molecule generation. However, these models have been criticized for producing physically implausible outputs. To address this issue, the researchers propose training a diffusion model with distorted molecules to improve the validity of generated molecules. The method is tested on various datasets and shows improvements in validity. This research has not yet undergone peer review. [Extracted from the article]

A preprint abstract from biorxiv.org discusses the discovery of antifungal compounds and the molecular mechanisms behind antifungal resistance. The study used a method called SAturated Transposon Analysis in Yeast (SATAY) to identify mutations that confer resistance to 20 different antifungal compounds. The research uncovered novel resistance mechanisms and multiple modes of action. The study also found that the antifungal Chitosan interacts with cell wall mannosylphosphate and that the transporter Hol1 concentrates the antifungal ATI-2307 within yeast. This research provides valuable insights for drug design and understanding cellular responses to chemical stresses. [Extracted from the article]

A recent study conducted by researchers at Osaka University in Japan explores the use of computer-aided drug design (CADD) in the field of drug discovery. The study focuses on the Fragment Molecular Orbital (FMO) method, a quantum chemical method that allows for precise energy calculations. The researchers highlight the potential of machine learning approaches in analyzing large computational data using the FMO method. This research has been peer-reviewed and provides valuable insights into the current status and future applications of CADD in drug development. [Extracted from the article]

A report from Xi'an Shiyou University in China discusses the synthesis of a novel compound called spirocyclic cyclopentapyridine, which plays a role in drug design and development. The researchers used commercially available 2-chloro-6-methoxypyridine as a starting material and achieved the synthesis through an eight-step reaction process, with a focus on the challenging steps of selective Negishi coupling and carbonyl reduction. The research has been peer-reviewed and provides valuable insights into the field of Obesity, Fitness, and Wellness. For more information, readers can contact the authors or access the full article through the provided DOI link. [Extracted from the article]

A study conducted by the Birla Institute of Technology in Jharkhand, India, explores the design and evaluation of novel triazole analogs as potential anti-retroviral and glucosamine-6-phosphate agents. The researchers used a multidisciplinary approach, including molecular docking, density functional theory analysis, molecular dynamics simulations, and predictive ADMET studies, to assess the binding interactions, stability, and drug-like properties of the compounds. The results indicate that one compound, RSA3, shows favorable binding interactions, stability, and significant affinity for target proteins, suggesting its potential as an anti-retroviral and glucosamine-6-phosphate agent. This research provides valuable insights into rational drug design strategies for the treatment of viral infections and related diseases. [Extracted from the article]

Researchers at the University of Bath in the United Kingdom have developed new urease inhibitors to prevent urinary catheter blockage. Catheter-associated urinary tract infections (CAUTI) caused by urease-positive organisms can lead to blockage of the catheter. The current urease inhibitor, acetohydroxamic acid (AHA), is rarely used due to its side effects. The researchers used a rational in silico drug design approach to identify and develop new urease inhibitors. One of the compounds, N,N'-Bis(3-pyridinylmethyl)thiourea (Bis-TU), outperformed AHA in activity assays and significantly extended the lifetime of the catheter in an in vitro bladder model. This cost-effective drug design approach could be used to target other diseases as well. [Extracted from the article]

Researchers at Shenyang Pharmaceutical University in China have developed a series of compounds that act as inhibitors for the Rho-associated coiled-coil containing kinase (ROCK), which plays a role in inflammation. One compound, DC24, was found to be the most effective inhibitor with selectivity for ROCK2 and demonstrated anti-inflammatory effects in an acute inflammation model. The research was supported by various funding sources and has been peer-reviewed. Further information can be obtained from the researchers at Shenyang Pharmaceutical University. [Extracted from the article]

A recent preprint abstract discusses the potential of inhibiting the mitochondrial deubiquitinase USP30 to protect dopaminergic neurons in Parkinson's disease. The researchers used chimeric protein engineering to obtain the crystal structure of human USP30 in complex with a specific inhibitor, revealing the molecular basis for its inhibition. They found that the inhibitor extends into a cryptic pocket facilitated by a compound-induced conformation of the USP30 switching loop. This study provides insights into the development of specific deubiquitinase inhibitors and offers a generalizable chimeric protein engineering strategy for structure-based drug design in neurodegeneration. However, it is important to note that this preprint has not yet undergone peer review. [Extracted from the article]

Vaccine adjuvants have evolved from empirical discovery to a more structured approach grounded in rational drug design. This paper explores the progression of adjuvant research, emphasizing the importance of understanding the structural and functional traits of adjuvants. Techniques such as X-ray crystallography and nuclear magnetic resonance (NMR) are used to establish structure-activity relationships (SARs) and aid in the design of superior adjuvants. The study also highlights the need for comprehensive immunological studies and the challenges in adjuvant research, while emphasizing the potential of adjuvants in treating autoimmune diseases and other conditions requiring immunological modulation. [Extracted from the article]

A preprint abstract from biorxiv.org discusses the use of machine learning techniques, specifically generative adversarial networks (GAN), in molecule generation for rational drug design. The authors propose a novel method called BEGAN (Boltzmann-Enhanced GAN) that adjusts molecule occurrence frequencies during training based on the Boltzmann distribution. This adjustment allows the GAN to explore molecular spaces with superior binding properties, potentially increasing the efficiency of drug discovery pipelines. The authors validate their approach by designing sex pheromone analogs targeting a specific pheromone receptor and conducting atomistic molecular dynamics simulations. However, it is important to note that this preprint has not been peer-reviewed. [Extracted from the article]

According to a preprint abstract from biorxiv.org, a new tool called MolSnapper has been developed for structure-based drug design. This tool integrates expert knowledge in the form of 3D pharmacophores to generate molecules that are better tailored to fit specific binding sites. Testing on various datasets has shown that MolSnapper produces molecules with high structural and chemical similarity to the original molecules, and it yields approximately twice as many valid molecules compared to alternative methods. It is important to note that this preprint has not yet undergone peer review. [Extracted from the article]

A recent study conducted at the University of Reading in the United Kingdom explores the potential of G-quadruplex DNA secondary structures in drug development. G-quadruplexes are formed in guanine-rich sequences and have been found to play a role in regulating biological processes, including oncogene promoters. The researchers highlight the interaction between G-quadruplex structures and metal complexes, emphasizing the importance of rational design in developing potent anticancer drugs. The study provides detailed structural insights into the binding modes of metal complex-G-quadruplex interactions. This research was supported by the Biotechnology and Biological Sciences Research Council (BBSRC) and has been peer-reviewed. [Extracted from the article]

The article discusses a novel approach to cancer treatment by intentionally overstimulating cancer cells to induce their destruction.

A preprint abstract from biorxiv.org discusses the use of sensitivity enhanced nuclear magnetic resonance (NMR) to investigate the structural characteristics of amyloid fibrils. The study found that the conformational preferences of flexible regions in amyloid fibrils are faithfully propagated in vitro and in cellular lysates. However, when amyloids are propagated inside cells, the minority conformation in the seeding population becomes predominant and more ordered, altering the conformational preferences of flexible regions. This research may contribute to a better understanding of protein misfolding disorders and aid in the development of structure-based drug design efforts. Please note that this preprint has not yet undergone peer review. [Extracted from the article]

A recent study conducted at Superior University in Punjab, Pakistan, focused on the development of a more affordable prosthetic suspension system for transtibial amputees. The researchers created and tested a locally-made Shuttle Lock suspension system, which was well-received by users. The system provided a comfortable, secure, and durable solution for transtibial prosthesis users, although some minor difficulties were noted. Overall, the study highlights the importance of a well-designed suspension system in improving the mobility and satisfaction of amputees. [Extracted from the article]

Researchers from Pfizer Worldwide R&D have developed a new in silico approach called PILOT for generating 3D ligand structures in structure-based drug design. This approach combines pocket conditioning with large-scale pre-training and property guidance to create ligands that exhibit desired chemical properties and maintain high synthetic accessibility. PILOT outperforms existing methods and has the potential to be a powerful tool for structure-based drug design. The research was supported by the European Union and the European Commission Joint Research Centre. [Extracted from the article]

A recent report from the University of Beira Interior in Covilha, Portugal discusses the importance of finding suitable biomarkers and modulators for prostate cancer (PCa) in order to improve prognosis. The report highlights the role of membrane proteins (MPs) in the development and progression of PCa and suggests that they could be potential therapeutic targets. The researchers propose the use of computational methods, such as structure-based drug design, to overcome experimental limitations and accelerate the discovery and optimization of biomarkers and inhibitors. This research has been peer-reviewed and provides insights into current breakthroughs in computer-aided drug design for PCa. [Extracted from the article]