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AstraZeneca researchers in Gothenburg, Sweden, conducted a study on the effect of gem-difluorination on the conformation and properties of a model macrocyclic system. The study found that the fluorinated macrocycle exhibited a trans amide in equilibrium with a cis amide, leading to decreased metabolic stability compared to the non-fluorinated counterpart. This research, supported by various organizations including AstraZeneca, provides insights into conformational controls of drug candidates for improved potency and ADME properties in the field of Obesity, Fitness, and Wellness. [Extracted from the article]

Research conducted at AstraZeneca in Gaithersburg, Maryland, has focused on developing analytical ion exchange chromatography methods for antibody drug conjugates (ADCs) containing the hydrolysis-prone succinimide-thioether conjugation chemistry. The study addressed the challenge of charge assay development in ADCs, which can be modified due to the change in net charge or surface charge after attaching a payload. Two approaches were explored to address this challenge: incubating ADCs under high pH conditions to drive complete hydrolysis and analyzing charge variants at the subunit level after IdeS digestion. The research successfully obtained acceptable charge profiles and quantitative integration results using both approaches. [Extracted from the article]

Researchers at AstraZeneca in Cambridge, United Kingdom, conducted a study on proteomics of prostate cancer using advanced technologies to analyze proteins in biofluids. The study compared medium-grade prostate cancer patients to healthy donors and identified differentially expressed proteins, including the upregulation of Prostate Specific Antigen (PSA) in the cancer cohort's serum. Further bioinformatics analysis revealed potential candidate proteins for future exploration. This research provides valuable insights into biomarkers and disease studies in prostate cancer. [Extracted from the article]

A recent study by AstraZeneca focused on the live attenuated influenza vaccine (LAIV) and its effectiveness against the A/H1N1pdm09 strain. The research aimed to develop a ferret efficacy model that could accurately predict clinical observations of vaccine effectiveness. The study found that optimizing the vaccine dose and using non-serological, clinically relevant protection endpoints in the ferret model successfully translated clinical data on H1N1 LAIV vaccine effectiveness. This research provides valuable insights into improving vaccine efficacy and development. [Extracted from the article]

AstraZeneca's research on Drugs and Therapies was presented at the EFGCP Annual Paediatric Conferences, focusing on improving children's access to innovative medicines. The conferences in 2021 and 2022 addressed challenges and progress in pediatric drug development, adapting to virtual formats due to the COVID-19 pandemic. Despite the virtual setting, the conferences maintained high attendance and valuable stakeholder participation, offering insights to optimize pediatric drug development. [Extracted from the article]

Researchers at AstraZeneca are focusing on cancer care, noting that cancer is projected to become the leading cause of death in the EU by 2035. Despite challenges such as an aging population and rising obesity rates, advancements in understanding cancer have led to potentially transformative treatments. The importance of collaboration and implementing new technologies in healthcare systems is emphasized to redefine cancer care for the future. For more information, readers can refer to the article "From Podium into Practice: Working Together to Revolutionise Cancer Care in the Real World" in EMJ Oncology. [Extracted from the article]

A recent study by AstraZeneca focused on assessing the robustness of oncology dose-finding trials using a modified Fragility Index (mFI). The research aimed to determine if the maximum tolerated dose (MTD) decision in phase I trials is sensitive to enrolling additional subjects. The results indicated that the mFI can be a valuable metric for evaluating the fragility of phase I trials and ensuring the robust identification of MTD. For more information, readers can access the full article in Cancers journal. [Extracted from the article]

Researchers at AstraZeneca in the United Kingdom have reported on a study exploring the combination of the Akt inhibitor Capivasertib and the Bcl-2 inhibitor Venetoclax in treating Diffuse Large B Cell Lymphoma (DLBCL). The study found that this combination showed therapeutic benefits in preclinical models of DLBCL, inducing tumor growth inhibition. The addition of rituximab further enhanced the treatment response in refractory DLBCL models, suggesting a potential treatment option for patients with DLBCL. [Extracted from the article]

Researchers at AstraZeneca conducted a study on the molecular and phenotypic characteristics of Respiratory Syncytial Virus (RSV) isolates recovered from medically vulnerable children participating in a clinical trial of nirsevimab. The study found that nirsevimab, an extended half-life monoclonal antibody, effectively neutralized RSV infections without any binding site substitutions affecting its efficacy. This research, supported by AstraZeneca and Sanofi, provides valuable insights into the prevention of RSV-associated lower respiratory tract disease in neonates and infants. [Extracted from the article]

Researchers at AstraZeneca in Cambridge, United Kingdom, have conducted a study on the monoclonal antibody Anifrolumab, which targets the type I interferon receptor. The study utilized a physiology-based pharmacokinetic model and relative transcriptomics to evaluate tissue distribution and receptor occupancy of Anifrolumab. The results of the study informed dosing strategies for phase III trials of Anifrolumab in new indications and demonstrated a novel approach to modeling the pharmacokinetics of therapeutic monoclonal antibodies. [Extracted from the article]

A study conducted by AstraZeneca in Gothenburg, Sweden, examined the impact of prior exacerbations in patients with Chronic Obstructive Pulmonary Disease (COPD) on healthcare resource utilization and related costs. The research found that patients with a history of exacerbations had higher healthcare resource utilization and costs compared to those without exacerbations. The study highlights the importance of managing and preventing exacerbations to optimize interventions and budgeting for related costs. [Extracted from the article]

Researchers from AstraZeneca conducted a study comparing the levels of respiratory syncytial virus (RSV) neutralizing antibodies in infants receiving nirsevimab versus palivizumab. The study found that nirsevimab conferred 10-fold higher and more sustained RSV nAb levels compared to palivizumab. This research provides valuable insights into potential prophylactic treatments for RSV infections in vulnerable populations. [Extracted from the article]

AstraZeneca has conducted research on the role of prostate-specific membrane antigen (PSMA) in the diagnosis and treatment of prostate cancer. PSMA is highly expressed in prostate cancer cells, making it a valuable target for imaging and therapy. The integration of PSMA-targeted imaging with radioligand therapy, known as theranostics, has shown significant improvements in the detection and management of advanced prostate cancer. This comprehensive review explores the latest developments in PSMA-targeted theranostics and their impact on the future of prostate cancer management, highlighting key clinical trials and emerging therapeutic strategies. [Extracted from the article]

A recent study conducted by AstraZeneca and published in Alimentary Pharmacology & Therapeutics provides recommendations for the detection, assessment, and management of drug-induced liver injury (DILI) in oncology clinical trials. The study highlights the challenges of monitoring cancer patients for hepatotoxicity and the lack of regulatory guidelines in this area. The recommendations are based on extensive literature review and consensus discussions among members of the IQ Consortium DILI Initiative, which includes representatives from 17 pharmaceutical companies, academic experts, and regulatory authorities. This review aims to provide evidence-based best practices for DILI management in oncology clinical trials. [Extracted from the article]

Severe asthma is a life-threatening condition that affects 7-11% of adults in Asian countries and 3-10% of adults worldwide. It causes symptoms such as difficulty breathing, wheezing, and coughing, and can lead to intense asthma attacks. Specialized treatment is required to manage severe asthma, and early diagnosis is crucial for better symptom management. Dedicated clinics and diagnostic tests are available to aid in the diagnosis and management of severe asthma. Patients are advised to consistently monitor their condition and consult healthcare professionals for proper management. [Extracted from the article]

A recent report by AstraZeneca explores the development of membrane-active peptide therapeutics in clinical oncology. Membrane-active peptides have been studied extensively and have shown potential in treating cancer. The report highlights five membrane-active peptide drugs that have entered preclinical or clinical phases and have shown promising results for cancer treatment. The research provides insights into the development of these peptide therapeutics and their potential in oncology. This information may be useful for library patrons conducting research on cancer treatment options. [Extracted from the article]

A new study on Artificial Intelligence (AI) in drug discovery, conducted by AstraZeneca in Gothenburg, Sweden, explores the role of protein kinases (PKs) in therapeutic intervention. PKs are enzymes that play a central role in signal transduction and have become major targets in various therapeutic areas, particularly cancer. The study highlights the abundance of PK/PK inhibitor (PKI) data available, thanks to open science initiatives, and the increasing use of AI in pharmaceutical research to analyze this data. The research concludes by examining the impact of AI approaches on PK drug discovery, particularly in relation to the increasing data orientation. [Extracted from the article]

A new report from AstraZeneca highlights the role of computational pathology in personalized cancer care. The incorporation of novel therapeutic agents in oncology, such as antibody-drug conjugates and chimeric antigen receptor cell therapies, represents a paradigm shift. Computational pathology allows for detailed assessment of target presence, expression levels, and phenotypic features of tumor cells and their surrounding microenvironment. The integration of artificial intelligence models in biomarker discovery and drug development shows promise in revolutionizing personalized medicine. [Extracted from the article]

A recent study conducted by researchers at AstraZeneca investigated the pharmacokinetics of poorly soluble compounds when administered intramuscularly as crystalline particles of different sizes. The study found that smaller particles of the drugs resulted in higher maximum plasma concentration and area under the plasma concentration-time profile. However, the relationship between particle size and exposure was more complex at lower doses. The study highlights the importance of understanding the physicochemical properties of the drug and the characteristics of the formulations. For more information, the full article can be accessed through the Journal of Pharmacy and Pharmacology. [Extracted from the article]

AstraZeneca has conducted a study on the safety and pharmacokinetics of nirsevimab, a monoclonal antibody against respiratory syncytial viruses (RSV), in immunocompromised children aged 24 months. The study found that nirsevimab was well tolerated with no safety concerns, and serum concentrations were supportive of efficacy in preventing medically attended RSV lower respiratory tract infections. Some children with increased nirsevimab clearance had conditions potentially associated with protein loss, but the impact on efficacy is unknown. This research has been peer-reviewed and provides valuable insights for the treatment of RSV in immunocompromised children. [Extracted from the article]

AstraZeneca researchers from Cambridge, United Kingdom have conducted a study on the genetic architecture of telomere length. Telomeres protect chromosome ends and are linked to human disease and aging. The researchers developed a joint telomere length metric using quantitative PCR and whole-genome sequencing measurements from 462,666 UK Biobank participants. Their findings identified novel genes and variants associated with telomere length, including genes associated with clonal hematopoiesis. This research has been peer-reviewed and published in Nature Genetics. [Extracted from the article]

AstraZeneca has published a report on drug development, highlighting the use of basket trials as a new approach. Traditionally, clinical trials focused on participants with the same disease, but the discovery of common therapeutic targets across different diseases has led to the development of basket trials. These trials allow for the evaluation of one therapy across multiple related diseases, using statistical tools like Bayesian borrowing to borrow information across diseases. The report provides a framework for implementing Bayesian borrowing in basket trials for successful drug development. [Extracted from the article]

The article presents the discussion on AstraZeneca on AZD4820, an oncolytic vaccinia virus engineered to express interleukin-12, which has shown enhanced antitumor activity by improving immune responses in tumors resistant to immune checkpoint inhibitors. Topics include the use of oncolytic viruses for cancer treatment, the role of interleukin-12 in modulating immune responses; and the combination of virus therapy with immune checkpoint blockade to improve treatment outcomes.

A study conducted by researchers from AstraZeneca in Cambridge, United Kingdom, examines the economic burden of chronic kidney disease (CKD) and kidney replacement therapy (KRT) across 31 countries/regions from 2022 to 2027. The study projects that the annual direct costs of diagnosed CKD and KRT will increase by 9.3% between 2022 and 2027, from $372.0 billion to $406.7 billion. By 2027, patients receiving KRT are projected to constitute 5.3% of the diagnosed CKD population but contribute 45.9% of the total costs. The findings of this study can inform healthcare resource allocation and future policy decisions. [Extracted from the article]

A new report discusses research conducted by AstraZeneca on the drug Mitiperstat and its effects on patients with impaired renal function. The study assessed the pharmacokinetics, safety, and tolerability of Mitiperstat in participants with severe renal impairment and normal renal function. The findings showed that participants with severe renal impairment had lower clearance of Mitiperstat compared to those with normal renal function. The study concluded that these findings, along with data from phase 2b, will guide the dosing regimen for phase 3. The research has been peer-reviewed and published in the British Journal of Clinical Pharmacology. [Extracted from the article]

A recent report discusses the use of artificial intelligence in drug discovery, specifically focusing on the role of phytochemicals. The researchers highlight the long history of phytochemicals in drug discovery and the recent advancements in analytical techniques that have made it easier to discover bioactive leads from natural compounds. They emphasize the importance of computational techniques such as molecular docking, QSAR modeling, machine learning, and network pharmacology in predicting the potential targets of natural products. The researchers also mention the use of LC-MS and LC-NMR to streamline compound identification. They conclude by discussing the emerging approach of machine learning, which involves interrelating phytochemical properties with diverse physiological activities. The article provides more information on this research and can be accessed for free. [Extracted from the article]

A recent study conducted by AstraZeneca in Gothenburg, Sweden, examined the impact of preanalytical factors on blood cell counts in patients with asthma. The study compared the performance of four different hematology analyzers and found that while all platforms provided comparable measurements of cell differentials on fresh blood, significant differences were observed after 24 hours, particularly for eosinophils. The study concluded that the choice of hematology analyzer, time window from sampling to analysis, and temperature conditions should be considered when analyzing blood cell differentials, especially for eosinophils. The findings highlight the importance of optimizing handling conditions depending on the specific cell type of interest and the hematology analyzer used. [Extracted from the article]

The article highlights a new study on chronic kidney disease (CKD), focusing on the association between hyperkalemia and the progression of the disease as well as mortality risks. Topics discussed include the increased risk of CKD progression and mortality in patients with hyperkalemia, the role of renin-angiotensin-aldosterone system inhibitors, and the study's use of real-world, propensity score-matched data to analyze outcomes.

A recent study conducted by researchers at AstraZeneca in Molndal, Sweden, has explored the role of antioxidants in the human lung. The study found that oxidative stress, caused by both internal and external factors, contributes to lung diseases. The researchers focused on the transcriptional factor NRF2, which regulates the antioxidant response in cells. They evaluated the overexpression of NRF2 using chemically modified RNAs and found successful expression in human cell lines and primary cells. The study provides insights into the dynamics of NRF2 in the human lung and suggests alternative approaches for pharmacological intervention. [Extracted from the article]

A recent case study conducted by AstraZeneca in Molndal, Sweden aimed to increase the exposure of a poorly soluble crystalline compound. Mice were given different formulations of the compound, and it was found that the addition of cremophor (CrEL) significantly increased the pharmacokinetic profile. The study suggests that finding an optimal screening vehicle early on for poorly water-soluble compounds can save time and resources in the development process. The research concludes that preclinical formulations can be used as indicators for amorphous solid dispersions (ASDs) in later stages of development. [Extracted from the article]

A study conducted by researchers at AstraZeneca explores the use of the Functional Assessment of Cancer Therapy item (FACT-GP5) as a measure of global treatment tolerability from the patient perspective. The study evaluates the responsiveness of the FACT-GP5 to key side-effects and the robustness of the measure to missing data assumptions. The results suggest that the FACT-GP5 can be a useful question for capturing the patient experience of drug tolerability, but missing assessments should be considered when interpreting the results. The study was supported by AstraZeneca and published in the journal Quality of Life Research. [Extracted from the article]

A recent study conducted by researchers at AstraZeneca in Cambridge, United Kingdom, explores the potential benefits of combining quantitative systems pharmacology (QSP) with artificial intelligence (AI) and machine learning (ML) in drug development. The researchers present four case examples where this symbiotic approach could provide new insights and potentially lead to breakthroughs in drug development. However, they also acknowledge the challenges associated with this approach, such as assessing and quantifying uncertainty, bias, and error. The successful implementation of this symbiotic approach has the potential to revolutionize drug development. [Extracted from the article]

A recent report from AstraZeneca highlights the use of biocatalysis in drug development. The researchers focused on using thermostable cytochrome P450 enzymes in bacterial membranes to replicate the metabolic pathways seen in human liver microsomes. This approach allows for the production of diverse metabolite structures and avoids the use of environmentally damaging solvents and transition metal catalysts. The study concludes that bacterial membranes provide an analogous system to liver microsomes for metabolite generation, with the added benefit of accessing a greater diversity of metabolite structures. [Extracted from the article]

AstraZeneca researchers have conducted a study on systemic lupus erythematosus (SLE), a chronic autoimmune disease characterized by inflammation. The study aimed to identify risk factors for SLE flares that require an inpatient or emergency department visit. The researchers analyzed Medicaid claims data from 2013 to 2019 and found that predictors of flares included ED visits in the previous year, SLE treatment progression to biologics, other neurological disorders, Black race, chronic kidney disease/renal failure, and opioid use. The study provides valuable insights for predicting and preventing SLE flares, which can reduce the burden on patients and healthcare systems. [Extracted from the article]

AstraZeneca researchers in Cambridge, United Kingdom have published a report on optimized LC-MS/MS methods for quantifying antibody-drug conjugate (ADC) payloads in cell culture media containing phenol red. Phenol red is commonly used in cell culture media but can impact instrument reliability during bioanalysis. The researchers compared different extraction methods to reduce phenol red matrix interferences and developed a precise and accurate method for measuring target analytes by LC-MS/MS. This method allows for continued bioanalytical support of in vitro models used in drug development. [Extracted from the article]

A recent study conducted by researchers from AstraZeneca in the United Kingdom focused on the impact of pregnancy on the pharmacokinetics of antiviral drugs. The study used Physiologically Based Pharmacokinetic (PBPK) modeling to simulate clinical studies and predict the pharmacokinetics of two drugs, lamotrigine and raltegravir, during pregnancy. The researchers successfully developed and validated a PBPK model for these drugs in pregnancy population models. This study provides valuable insights into how pregnancy affects the disposition of drugs and may contribute to the future prediction of pharmacokinetics in pregnant individuals. [Extracted from the article]

A new report summarizes the safety data on Nirsevimab, a drug developed by AstraZeneca, for the prevention of respiratory syncytial virus (RSV) in infants and children. The drug is approved in the US for use in neonates, infants, and children up to 24 months old who are at risk of severe RSV disease. The analysis of three randomized controlled trials showed that Nirsevimab had a favorable safety profile, with most adverse events being mild to moderate and unrelated to treatment. The research concludes that a single dose of Nirsevimab per season is effective and safe for preventing RSV disease in this population. [Extracted from the article]

This article discusses new findings in the field of immunology, specifically focusing on bispecific antibodies. Bispecific antibodies have the ability to target multiple disease-associated antigens or engage immune cells, presenting both advantages and challenges compared to using two separate biological products. The article reviews clinical studies of FDA-approved bispecific antibodies in oncology and identifies dose-related strategies for clinical dose optimization and regulatory approvals. The research aims to inform successful strategies for future bispecific antibody development. The study was supported by AstraZeneca and has been peer-reviewed. [Extracted from the article]

A recent report from AstraZeneca, a pharmaceutical company based in Cambridge, United Kingdom, discusses the identification and evaluation of reversible covalent binders to Cys55 of Bfl-1, a protein overexpressed in tumors. The researchers used a DNA-encoded chemical library screen to identify the first known reversible covalent small-molecule ligand for Bfl-1. The binding was validated through biophysical and biochemical techniques, confirming the reversible covalent mechanism of action. The research provides insights into covalent drug discovery and highlights opportunities for further exploration in this field. [Extracted from the article]

A recent study conducted by investigators at AstraZeneca has found that tezepelumab, a medication used to treat severe, uncontrolled asthma, significantly reduces asthma exacerbations compared to a placebo. The study analyzed the efficacy of tezepelumab in various clinically relevant subgroups of patients and found that reductions in exacerbations were observed across a wide range of patient characteristics. The findings support the benefits of tezepelumab in patients with severe, uncontrolled asthma and can help inform healthcare providers' treatment decisions. The study was funded by AstraZeneca and has been peer-reviewed. [Extracted from the article]