Drug Development - Science topic

Selective cyclooxygenase-2 inhibitors have gained prominence in anti-inflammatory drug development due to their potential to reduce inflammation while minimizing the gastrointestinal toxicity associated with non-selective NSAIDs. This study focuses on the synthesis, molecular docking, characterization, and evaluation of new 3-ethyl-1H-indole deriva...

Background Brain–gut behaviour therapies (BGBT) have gained widespread acceptance as therapeutic modalities for the management of disorders of gut–brain interaction (DGBI). However, existing treatment evaluation methods in the medical field fail to capture the specific elements of scientific rigour unique to behavioural trial evaluation. Aims To o...

Macrocycles are increasingly considered as promising modalities to target challenging intracellular proteins. However, strategies for transitioning from active linear starting points to improved macrocycles are still underdeveloped. Here we explored the derivatization of linkers as an approach for macrocycle optimization. Using the FK506‐binding pr...

Plant sesterterpenoids are an extremely rare family of natural products that generally possess novel chemical structures and diverse biological activities. Herein, we report the discovery of an unprecedented group of minor plant sesterterpenoids, gracilisoids B−E (2–5), which feature two types of highly functionalized bicyclo[3.2.0]heptane carbon s...

ABCA1 (ATP-binding cassette transporter A1) is a crucial membrane protein involved in lipid homeostasis and reverse cholesterol transport. This paper explores the molecular mechanisms, clinical relevance, and potential of ABCA1 as a therapeutic target. By examining its role in diseases such as atherosclerosis, Alzheimer's disease, and metabolic dis...

The antimicrobial properties of silver and silver complexes have been known in medicine since ancient times. However, limitations in stability and solubility have impaired medicinal chemistry and drug development research. With the advent of N-heterocyclic carbenes (NHC) as ligands, the development of synthesis methods for organometallic silver spe...

Apigenin, a natural flavonoid prevalent in a variety of fruits, vegetables, and herbs, has attracted significant interest due to its wide range of pharmacological effects and therapeutic potential. This review aims to provide an in-depth analysis of apigenin from both preclinical and clinical perspectives, emphasizing its diverse roles in health ma...

Leishmaniasis is a parasitic disease caused by protozoan organisms belonging to the Leishmania genus, affecting many individuals worldwide, with the burden surpassing one million cases. This disease leads to considerable morbidity and mortality, predominantly within tropical and subtropical regions. The current therapeutic options for leishmaniasis...

Background Large-scale pharmacogenomic resources, such as the Connectivity Map (CMap), have greatly assisted computational drug discovery. However, despite their widespread use, CMap-based methods have thus far been agnostic to the biological activity of drugs as well as to the genomic effects of drugs in multiple disease contexts. Here, we present...

Hydrodynamic radius (R H ) is a descriptive metric of protein structure with the potential to impact drug development, disease diagnosis, and other important research areas of molecular biology. Common instrumental methods...

Transient receptor potential (TRP) melastatin 4 (TRPM4) protein is a calcium-activated monovalent cation channel associated with various genetic and cardiovascular disorders. The anthranilic acid derivative NBA is a potent and specific TRPM4 inhibitor, but its binding site in TRPM4 has been unknown, although this information is crucial for drug dev...

Phosphatidylinositol 5‐phosphate 4‐kinases (PI5P4K), also known as type II PIPKs or PIPKIIs, convert the lipid second messenger PI5P to PI(4,5)P2. The PI5P4K family consists of three isozymes in mammals—PI5P4Kα, β, and γ—which notably utilize both GTP and ATP as phosphodonors. Unlike the other two isozymes, which can utilize both ATP and GTP, PI5P4...

Globally, cardiovascular diseases remain among the leading causes of mortality, highlighting the urgent need for innovative research models. Consequently, the development of accurate models that simulate cardiac function holds significant scientific and clinical value for both disease research and therapeutic interventions. Cardiac organoids, which...

Deconvoluting drug targets is crucial in modern drug development, yet both traditional and artificial intelligence (AI)-driven methods face challenges in terms of completeness, accuracy, and efficiency. Identifying drug targets, especially within complex systems such as the p53 pathway, remains a formidable task. The regulation of this pathway by m...

The benzodiazepines (BZ) bind to the GABAA receptor (GABAAR) at the interface of its α/γ subunits and exert pharmacological activity as allosteric modulators. However, the distribution of the six distinct α subunits (α1 – α6) in the human brain has not been mapped in detail, primarily due to lack of α-subunit selective radioligands. AZD7325 and AZD...

Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal disorder of unknown etiology, characterized by interstitial fibrosis of the lungs. Bleomycin-induced pulmonary fibrosis mouse model (BLM model) is a widely used animal model to evaluate therapeutic targets for IPF. Histopathological analysis of lung fibrosis is an important m...

Chemical biology is a multidisciplinary subject that combines ideas from chemistry and biology to investigate the molecular mechanisms underlying physiological and pathological tactics. In drug discovery, chemical biology plays a pivotal function in elucidating the difficult interactions among small molecules and organic macromolecules, presenting...

Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease and is closely associated with metabolic diseases such as obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome. However, effective treatment strategies for NAFLD are still lacking. In recent years, progress has been made in understanding the patho...

The partition coefficient (log P) is a critical parameter that measures the balance between hydrophilicity and lipophilicity of molecules, playing a key role in molecular material design and drug development. Developing accurate, efficient, and computationally simple models for log P prediction is essential for advancing drug discovery and material...

Viral adhesion to host cells is a critical step in infection for many viruses, including monkeypox virus (MPXV). In MPXV, the H3 protein mediates viral adhesion through its interaction with heparan sulfate (HS), yet the structural details of this interaction have remained elusive. Using AI-based structural prediction tools and molecular dynamics (M...

The three-year COVID-19 pandemic ‘has’ caused a wide range of medical, social, political, and financial implications. Since the end of 2020, various mutations and variations in SARS-CoV-2 strains, along with the immune escape phenomenon, have emerged. There is an urgent need to identify a relatively stable target for the development of universal va...

Chronic kidney disease (CKD) and hypertension are interconnected, worsening each other. Recent studies have shown that the reduction of peroxiredoxin 5 (Prdx5) accelerates kidney fibrosis, a hallmark of CKD. This study aims to observe whether the deficiency of Prdx5 also contributes to the worsening of CKD-related hypertension. Angiotensin II (Ang...

Aging is one of the most significant risk factors for breast cancer. With the growing interest in the alterations of the aging breast tissue microenvironment, it is identified that aging is related to tumorigenesis, invasion, and drug resistance. However, current pre‐clinical disease models often neglect the impact of aging and sometimes result in...

Background The receptor tyrosine kinase (RTK)/Ras/Raf/MEK/ERK signaling pathway is one of the most tumorigenic pathways in cancer, with its hyperactivation strongly linked to the aggressive nature of glioblastoma (GBM). Although extensive research has focused on developing therapeutics targeting this pathway, clinical success remains elusive due to...

Exposure-response (ER) analyses are routinely performed as part of model-informed drug development to evaluate the risk-to-benefit ratio for dose selection, justification, and confirmation. For logistic regression analyses with binary endpoints, several exposure metrics are investigated, based on pharmacological plausibility, including time-average...

As a structural and catalytic cofactor, copper is involved in many biological pathways and is required for the biochemistry of all living organisms. However, excess intracellular copper can induce cell death due to its potential to catalyze the generation of reactive oxygen species, thus copper homeostasis is strictly regulated. And the deficiency...

Challenges in drug development for rare diseases such as pulmonary arterial hypertension can be addressed through the use of mathematical modeling. In this study, a quantitative systems pharmacology model of pulmonary arterial hypertension pathophysiology and pharmacology was used to predict changes in pulmonary vascular resistance and six-minute w...

This study investigated the success rate of Phase 1 clinical trial entry and the factors influencing it in oncology projects involving academia–industry collaboration during the discovery and preclinical stages. A total of 344 oncology projects in the discovery stage and 360 in the preclinical stage, initiated through collaborations with universiti...

Dorsal root ganglion (DRG) neurons play a crucial role in the perception and modulation of pain signals, making them a critical focus in pain mechanism research. Opioid receptors, as classical analgesic targets, inhibit pain signals by regulating ion channels such as calcium channels, while ion channels are directly involved in the generation and t...

Background/Objectives: Acute myeloid leukemia (AML) presents significant therapeutic challenges, particularly in cases driven by mutations in the FLT3 tyrosine kinase. This study aimed to develop a robust and user-friendly machine learning-based quantitative structure–activity relationship (QSAR) model to predict the inhibitory potency (pIC50 value...

Transient receptor potential channel subfamily M member 3 (TRPM3) is a Ca²⁺-permeable cation channel activated by the neurosteroid pregnenolone sulfate (PregS) or heat, serving as a nociceptor in the peripheral sensory system. Recent discoveries of autosomal dominant neurodevelopmental disorders caused by gain-of-function mutations in TRPM3 highlig...

Drug repositioning offers a promising route to increase the efficacy and streamline the development of pharmaceutical treatments. With the high costs and extensive time frames associated with traditional drug development pathways, computational approaches have risen as pivotal alternatives. This paper surveys the latest network-based methodologies...

Monoclonal antibodies (mAbs) are critical components in the therapeutic landscape, but their dosing strategies often evolve post‐approval as new data emerge. This review evaluates post‐marketing label changes in dosing information for FDA‐approved mAbs from January 2015 to September 2024, with a focus on both initial and extended indications. We sy...

With the aim of developing novel anti-SARS-CoV-2 drugs to address the ongoing evolution and emergence of drug-resistant strains, the reported SARS-CoV-2 Mpro inhibitor WU-04 was selected as a lead to find novel, highly potent, and broad-spectrum inhibitors. Using a fragment-based multilevel virtual screening strategy, 15 hit compounds were identifi...

Despite advances in various chemotherapy regimens, current therapeutic options are limited for ovarian cancer patients. Oxidative stress-induced growth inhibitor 1 (OSGIN1), which is a tumor suppressor gene known to regulate the cellular stress response and apoptosis, is associated with ovarian cancer development. However, the underlying mechanisms...

In this study, we explore the potential of the difluoro(trifluoromethoxy)methyl group, CF2–O–CF3, an underexplored but promising structural analog of the trifluoromethoxy group (OCF3). This moiety offers unique electronic properties and enhanced chemical stability due to its multiple C–F bonds, along with the added advantage of C–O bond cleavage, m...

Background: Lappula patula (L. patula) is a plant with known medicinal properties, and its extracts have shown promise as potential anti-cancer agents. This study aimed to evaluate the nematocidal effects of L. patula extracts and investigate their impact on germline development, DNA damage responses, and apoptosis in Caenorhabditis elegans (C. ele...

Background Interleukin 17 (IL-17) plays a crucial role in regulating the immune system and is associated with numerous diseases. Modulating IL-17 levels has demonstrated potential in mitigating disease symptoms, positioning it as a compelling target for drug development. Therefore, identifying and characterizing novel drug molecules capable of infl...

Drug delivery to the brain, restricted by the blood-brain barrier (BBB), remains one of the major obstacles in central nervous system (CNS) drug development. Solute carriers and ATP-binding cassette family (ABC) transporters expressed at the BBB play crucial roles in drug delivery to the brain. Knowledge about brain transporters and the receptors e...

Background Drug and protein targets affect the physiological functions and metabolic effects of the body through bonding reactions, and accurate prediction of drug-protein target interactions is crucial for drug development. In order to shorten the drug development cycle and reduce costs, machine learning methods are gradually playing an important...

Plain language summary Five years of progress: from zero to many therapeutic treatments in development for SYNGAP1-Related Disorder, a Patient Organization Perspective from SynGAP Research Fund. SYNGAP1-related disorder (SRD) is a rare condition that is caused by accidental changes in the SYNGAP1 gene. It is one of many rare disorders that happen w...

The evolution of antitumor drug development has transitioned from single‐agent chemotherapy to targeted therapy, immunotherapy, and more recently, multispecific drugs. These innovative drugs target multiple cellular or molecular pathways simultaneously, offering a more comprehensive anticancer approach and addressing some of the limitations inheren...

Network pharmacology plays a pivotal role in systems biology, bridging the gap between traditional Chinese medicine (TCM) theory and contemporary pharmacological research. Network pharmacology enables researchers to construct multilayered networks that systematically elucidate TCM’s multi-component, multi-target mechanisms of action. This review su...

Predicting the impact of single-point amino acid mutations on protein stability is essential for understanding disease mechanisms and advancing drug development. Protein stability, quantified by changes in Gibbs free energy ($\Delta\Delta G$), is influenced by these mutations. However, the scarcity of data and the complexity of model interpretation...

The nucleophilic reaction between phosphorothioate oligonucleotides and electrophilic reagents has become a cost‐effective and efficient approach for oligonucleotide functionalization. This method allows for the precise incorporation of desired chemical structures at specific sites on the phosphorothioate backbone through conjugation with electroph...

Predicting drug–target interactions (DTIs) is a crucial step in the development of new drugs and drug repurposing. In this paper, we propose a novel drug–target prediction model called MCF-DTI. The model utilizes the SMILES representation of drugs and the sequence features of targets, employing a multi-scale convolutional neural network (MSCNN) wit...

Ground-breaking awareness has been reached about the intricate and dynamic connection between developing tumors and the host immune system. Being a powerful arm of innate immunity and a functional bridge with adaptive immunity, the complement system (C) has also emerged as a pivotal player in the tumor microenvironment (TME). Its “double-edged swor...

With the increase of drug research and development activities, the demand for resources for clinical medical experimental research grows year by year, and the traditional biological experimental methods can no longer meet the requirements of saving the existing resources, so this paper proposes a new method combining protein drug structure predicti...

Introduction The sales patterns of original drugs after patent expiration in Korea show a relatively high market share and continuous sales growth differently from those in the U.S. and European countries. This study aims to investigates a five-year sales pattern of original drugs after patent expiration in Korea using empirical data. Methods Usin...

Drug development faces significant financial and time challenges, highlighting the need for more efficient strategies. This study evaluated the druggability of the entire human proteome using Fpocket. We identified 15,043 druggable pockets in 20,255 predicted protein structures, significantly expanding the estimated druggable proteome from 3000 to...

The pharmaceutical industry constantly strives to improve drug development processes to reduce costs, increase efficiencies, and enhance therapeutic outcomes for patients. Model‐Informed Drug Development (MIDD) uses mathematical models to simulate intricate processes involved in drug absorption, distribution, metabolism, and excretion, as well as p...

Vascular endothelial growth factor (VEGF), also known as VEGF-A, has been linked to various diseases, such as wet age-related macular degeneration (wAMD) and cancer. Even though there are VEGF inhibitors that are currently commercially available in clinical applications, severe adverse effects have been associated with these treatments. There is st...

Type II nuclear receptors (T2NRs) require heterodimerization with a common partner, the retinoid X receptor (RXR), to bind cognate DNA recognition sites in chromatin. Based on previous biochemical and overexpression studies, binding of T2NRs to chromatin is proposed to be regulated by competition for a limiting pool of the core RXR subunit. However...

Early approval mechanisms, such as conditional approval in the EU, have been used extensively to provide timely access to therapeutic innovations to cancer patients with unmet medical needs. While based on promising early evidence, such approvals are challenging from many perspectives due to the lack of comprehensive data. The limitation typically...

The emergence of artificial intelligence (AI) in drug discovery represents a transformative development in addressing neglected diseases, particularly in the context of the developing world. Neglected diseases, often overlooked by traditional pharmaceutical research due to limited commercial profitability, pose significant public health challenges...

Background Age, female sex and the APOEe4 allele are among the top risk factors for developing late‐onset Alzheimer’s disease (LOAD). Precision medicine for AD drug development necessitates targeting specific biological pathways driving AD pathology. We previously identified LOAD‐associated transcriptomic signatures specific to both sex and APOE ge...

Background Recent advancements in Alzheimer’s disease (AD) biomarker research and AD drug trials prompt reflection on the value and appropriate use of tau‐PET in future clinical practice and trials. We therefore conducted a survey among dementia and PET experts worldwide to investigate how they envision the future role of tau‐PET in clinical practi...

Background The early detection of neurologic damage at the microscopic level when the disease is subclinical would facilitate intervention preventing progression or potentially reversing the condition. The early determination of drug efficacy could shorten the length of drug studies, thereby reducing research costs. The eye is the only place in the...

Background The early detection of neurologic damage at the microscopic level when the disease is subclinical would facilitate intervention preventing progression or potentially reversing the condition. The early determination of drug efficacy could shorten the length of drug studies, thereby reducing research costs. The eye is the only place in the...

Alzheimer's disease, AD, has been a difficult problem for relevant experts and patients since its discovery. As a neurodegenerative disease, it can lead to cognitive decline and seriously affect the patient's life. In recent years, with the aging of the world's population, and the combination of various factors, the prevalence of Alzheimer's diseas...

Drug discovery and drug development were two complex process to find new drugs. Advance science of medicine after human genome project were established accelerating the development of new field called bionformatics. Currently, bioinformatics integrated multidisciplinary studies including molecular biology, mathematics and information engineering. T...

Liver cancer is a leading cause of cancer-related deaths worldwide, highlighting the need for innovative approaches to understand its complex biology and develop effective treatments. While traditional in vivo animal models have played a vital role in liver cancer research, ethical concerns and the demand for more human-relevant systems have driven...

Background Age, female sex and the APOEε4 allele are among the top risk factors for developing late‐onset Alzheimer’s disease (LOAD). Precision medicine for AD drug development necessitates targeting specific biological pathways driving AD pathology. We previously identified LOAD‐associated transcriptomic signatures specific to both sex and APOE ge...

Background Qualitative patient interviews are increasingly conducted alongside clinical trials; interviews administered early in drug development can yield insight into the patient journey. Examination among patient subgroups may identify factors that influence the patient experience, including trial participation. As part of the INTERCEPT‐AD phase...

This review explores both the positive and negative impacts of chemistry on society, focusing on the intersection between pharmaceutical, natural, and synthetic chemicals. On the one hand, drugs developed through medicinal chemistry have saved lives, improved people’s quality of life, and increased longevity. However, they also pose risks, includin...