845,395 results match your criteria drug development

Combining immunotherapy with an epidrug in squamous cell carcinomas of different locations: rationale and design of the PEVO basket trial.

ESMO Open 2021 Apr 14;6(3):100106. Epub 2021 Apr 14.

Department of Drug Development and Innovation (D3i), Institut Curie, Paris, France; Inserm U900 Research Unit, Saint Cloud, France; Paris-Saclay University, Paris, France. Electronic address:

Squamous cell carcinomas (SCCs) are among the most frequent solid tumors in humans. SCCs, related or not to the human papillomavirus, share common molecular features. Immunotherapies, and specifically immune checkpoint inhibitors, have been shown to improve overall survival in multiple cancer types, including SCCs. Read More

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Investigation of protein-ligand complexes by ligand-based NMR methods.

Carbohydr Res 2021 Apr 9;503:108313. Epub 2021 Apr 9.

Dipartimento di Scienze Chimiche, Complesso Universitario Monte Sant'Angelo, Università di Napoli Federico II, Via Cintia 4, I-80126, Napoli, Italy; CNR, Institute for Polymers, Composites and Biomaterials, IPCB ss, Catania, Italy. Electronic address:

Molecular recognition is at the base of all biological events and its knowledge at atomic level is pivotal in the development of new drug design approaches. NMR spectroscopy is one of the most widely used technique to detect and characterize transient ligand-receptor interactions in solution. In particular, ligand-based NMR approaches, including NOE-based NMR techniques, diffusion experiments and relaxation methods, are excellent tools to investigate how ligands interact with their receptors. Read More

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Targeting of myeloid-derived suppressor cells by all-trans retinoic acid as host-directed therapy for human tuberculosis.

Cell Immunol 2021 Apr 8;364:104359. Epub 2021 Apr 8.

DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medical and Health Sciences, Stellenbosch University, Cape Town, South Africa. Electronic address:

Conventional anti-tuberculosis (TB) therapies comprise lengthy antibiotic treatment regimens, exacerbated by multi-drug resistant and extensively drug resistant mycobacterial strains. We assessed the ability of all-trans retinoic acid (ATRA), as repurposed compound serving as host-directed therapy (HDT), to counteract the suppressive effects of myeloid-derived suppressor cells (MDSCs) obtained from active TB cases (untreated or during week one of treatment) on T-cell responsiveness. We show for the first time that MDSCs suppress non-specific T-cell activation and production of interleukin (IL)-2, IL-4, IL-13 and GM-CSF via contact-dependent mechanisms. Read More

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Psychotic symptoms in drug resistant epilepsy patients after cortical stimulation.

Epilepsy Res 2021 Apr 2;173:106630. Epub 2021 Apr 2.

Epilepsy Program, Neurology Department, Hospital Clinic of Barcelona, Barcelona, 08036, Spain; Clinical Institute of Neurosciences, Hospital Clinic of Barcelona, Barcelona, 08036, Spain; Biomedical Research Institute August Pi i Sunyer (IDIBAPS), Hospital Clinic of Barcelona, Barcelona, 08036, Spain.

Purpose: The use of invasive EEG (iEEG) recordings before epilepsy surgery has increased as more complex focal epilepsies are evaluated. Psychotic symptoms (PS) during iEEG have been scarcely reviewed. We aim to report our series of patients with psychotic symptoms (PS) brought about by cortical stimulation (CS) and to identify triggers. Read More

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Multi-scale modeling for systematically understanding the key roles of microglia in AD development.

Comput Biol Med 2021 Apr 5;133:104374. Epub 2021 Apr 5.

School of Biomedical Informatics, The University of Texas Health Science Center at Houston, 7000 Fannin Street, Houston, TX, 77030, USA. Electronic address:

Alzheimer's disease (AD) is the leading cause of age-related dementia, affecting over 5 million people in the United States. Unfortunately, current therapies are largely palliative and several potential drug candidates have failed in late-stage clinical trials. Studies suggest that microglia-mediated neuroinflammation might be responsible for the failures of various therapies. Read More

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Long-term functional alterations following prenatal GLP-1R activation.

Neurotoxicol Teratol 2021 Apr 14:106984. Epub 2021 Apr 14.

Department of Biomedical Sciences and Center for Brain Repair, Florida State University College of Medicine, Tallahassee, FL 32306, United States of America. Electronic address:

Evidence supporting the use of glucagon-like peptide-1 (GLP-1) analogues to pharmacologically treat disorders beyond type 2 diabetes and obesity is increasing. However, little is known about how activation of the GLP-1 receptor (GLP-1R) during pregnancy affects maternal and offspring outcomes. We treated female C57Bl/6 J mice prior to conception and throughout gestation with a long-lasting GLP-1R agonist, Exendin-4. Read More

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Polymeric lipid hybrid nanoparticles as a delivery system enhance the antitumor effect of Emodin in vitro and in vivo.

J Pharm Sci 2021 Apr 14. Epub 2021 Apr 14.

College of Pharmacy, Jinan University, Guangzhou, 510632, China; International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), School of Pharmacy, Jinan University, Guangzhou, 510632, China; Cancer Research Institute of Jinan University, Guangzhou, 510632, China; Interventional Cancer Institute of Chinese Integrative Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China. Electronic address:

This study aimed to evaluate the therapeutic efficacy of Emodin-loaded polymer lipid hybrid nanoparticles (E-PLNs) for breast cancer. The size, Zeta potential, surface morphology, encapsulation efficiency, stability, in vitro drug release of E-PLNs prepared by the nanoprecipitation method were characterized. The uptake, in-vitro cytotoxicities and apoptosis of free drug, E-PLNs were investigated against MCF-7 cells. Read More

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Pharmacokinetics of Opicapone and Its Metabolites in Healthy White and Chinese Subjects.

Clin Pharmacol Drug Dev 2021 Apr 17. Epub 2021 Apr 17.

Clinical Trial Center, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Assessment of Clinical Drugs Risk and Individual Application Key Laboratory, Chinese Academy of Medical Sciences, Beijing, China.

Opicapone (OPC) is a third-generation catechol-O-methyltransferase inhibitor developed to treat Parkinson disease and motor fluctuations. This open-label, single-center, phase 1 study aimed to evaluate the pharmacokinetics (PK) of OPC and its metabolites when administered as single and multiple doses in healthy White and Chinese subjects. The study enrolled a total of 30 White and Chinese healthy subjects, equally balanced among groups. Read More

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Establishment of The Tandem Mass Spectrometric Fingerprints of Taxane-Based Anticancer Compounds.

Rapid Commun Mass Spectrom 2021 Apr 17:e9107. Epub 2021 Apr 17.

College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK, Canada.

Compounds in the taxane drug family are among the most successful and effective chemotherapeutic agents used for the treatment of solid tumors, such as breast, ovarian, and prostate cancers. The tandem mass spectrometric (MS/MS) fragmentation behavior of these compounds are described in detail and a generalized MS/MS fingerprint is established for the first time. Five compounds were evaluated, namely paclitaxel, docetaxel, cabazitaxel, cephalomannine, and Baccatin III. Read More

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High-throughput screening identifies established drugs as SARS-CoV-2 PLpro inhibitors.

Protein Cell 2021 Apr 17. Epub 2021 Apr 17.

Shanghai Institute for Advanced Immunochemical Studies and School of Life Science and Technology, ShanghaiTech University, Shanghai, 201210, China.

A new coronavirus (SARS-CoV-2) has been identified as the etiologic agent for the COVID-19 outbreak. Currently, effective treatment options remain very limited for this disease; therefore, there is an urgent need to identify new anti-COVID-19 agents. In this study, we screened over 6,000 compounds that included approved drugs, drug candidates in clinical trials, and pharmacologically active compounds to identify leads that target the SARS-CoV-2 papain-like protease (PLpro). Read More

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Nocardioides luti sp. nov., belonging to the family Nocardioidaceae isolated from kaolinite, exhibiting the biosynthesis potential of alkylresorcinol.

Antonie Van Leeuwenhoek 2021 Apr 17. Epub 2021 Apr 17.

Department of Bioengineering and Nano-Bioengineering, Graduate School of Incheon National University, Incheon, 22012, Republic of Korea.

A novel Gram-staining-positive, short rod-shaped, non-motile, and non-pigmented actinobacterial strain (KIGAM211) was isolated from kaolinite, a soft white clay mineral, collected from Sancheong in the Republic of Korea. On the basis of 16S rRNA gene sequence analysis, strain KIGAM211 was determined to belong to the genus Nocardioides and was most closely related to N. ungokensis UKS-03 (97. Read More

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Halobellus ruber sp. nov., a deep red-pigmented extremely halophilic archaeon isolated from a Korean solar saltern.

Antonie Van Leeuwenhoek 2021 Apr 17. Epub 2021 Apr 17.

Department of Bioengineering and Nano-Bioengineering, Graduate School of Incheon National University, Incheon, 22012, Republic of Korea.

A novel halophilic archaeon, strain MBLA0160, was isolated from a solar saltern in Sorae, Republic of Korea. The cells are deep-red pigmented, Gram-negative, rod shaped, motile, and lysed in distilled water. The strain MBLA0160 grew at 25-45 °C (optimum 37 °C), in 15-30% (w/v) NaCl (optimum 20%) and 0. Read More

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A review: hippo signaling pathway promotes tumor invasion and metastasis by regulating target gene expression.

J Cancer Res Clin Oncol 2021 Apr 17. Epub 2021 Apr 17.

School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450001, China.

Background: The Hippo pathway is widely considered to inhibit cell growth and play an important role in regulating the size of organs. However, recent studies have shown that abnormal regulation of the Hippo pathway can also affect tumor invasion and metastasis. Therefore, finding out how the Hippo pathway promotes tumor development by regulating the expression of target genes provides new ideas for future research on targeted drugs that inhibit tumor progression. Read More

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Structural MRI substrate of long-duration response to levodopa in Parkinson's disease: an exploratory study.

J Neurol 2021 Apr 17. Epub 2021 Apr 17.

Department of Medical, Surgical Sciences and Advanced Technologies "GF Ingrassia", University of Catania, Via Santa Sofia 78, 95123, Catania, Italy.

Objective: The long-duration response (LDR) to L-dopa is a sustained benefit deriving from chronic administration of therapy to patients with Parkinson's disease (PD). Almost all patients with early PD may develop the LDR to L-dopa, even if some patients could not at given dosages of the drug. Aim of this exploratory study is to investigate whether a neuroanatomical substrate may underlie the development of the of LDR using structural magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) analysis. Read More

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Instructive roles of astrocytes in hippocampal synaptic plasticity: neuronal activity-dependent regulatory mechanisms.

FEBS J 2021 Apr 17. Epub 2021 Apr 17.

Division of Life Science, The Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.

In the adult hippocampus, synaptic plasticity is important for information processing, learning, and memory encoding. Astrocytes, the most common glial cells, play a pivotal role in the regulation of hippocampal synaptic plasticity. While astrocytes were initially described as a homogenous cell population, emerging evidence indicates that in the adult hippocampus, astrocytes are highly heterogeneous and can differentially respond to changes in neuronal activity in a subregion-dependent manner to actively modulate synaptic plasticity. Read More

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Pharmacovigilance network as an additional tool for the surveillance of antimicrobial resistance.

Pharmacoepidemiol Drug Saf 2021 Apr 17. Epub 2021 Apr 17.

Department de Farmacologia, Terapèutica i Toxicologia. Universitat Autònoma de Barcelona (UAB), Spain.

Background: The WHO Programme for International Drug Monitoring (PIDM) is a large Pharmacovigilance network of countries sharing Adverse Drug Reaction (ADR) reports. Pharmacovigilance Experts have suggested that antimicrobial resistance (AMR) is an overlooked adverse event. We undertook this study to investigate the potential role of Pharmacovigilance databases in the surveillance of antimicrobial resistance. Read More

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Design, synthesis and biological evaluation of N-substituted indole-thiazolidinedione hybrid analogues as potential pancreatic lipase inhibitors.

Chem Biol Drug Des 2021 Apr 16. Epub 2021 Apr 16.

Laboratory of Natural Product Chemistry, Department of Pharmacy, Birla Institute of Technology and Science, Pilani (BITS Pilani), Pilani Campus, Pilani - 333 031, Rajasthan, India.

Pancreatic Lipase (PL) is a key enzyme responsible for 50-70% of dietary triglycerides, hence its inhibition is considered as a viable approach for the management of obesity. A series of indole-TZD hybrid analogues were synthesised, characterised, and evaluated for their PL inhibitory activity. Knoevenagel condensation of various substituted indole-3-carboxaldehyde with substituted thiazolidinediones resulted in the formation of titled analogues. Read More

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Model-Based Estimation of Iohexol Plasma Clearance for Pragmatic Renal Function Determination in the Renal Transplantation Setting.

Clin Pharmacokinet 2021 Apr 17. Epub 2021 Apr 17.

Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Albinusdreef 2, 2333ZA, Leiden, the Netherlands.

Background: Iohexol plasma clearance-based glomerular filtration rate (GFR) determination provides an accurate method for renal function evaluation. This technique is increasingly advocated for clinical situations that dictate highly accurate renal function assessment, as an alternative to conventional serum creatinine-based methods with limited accuracy or poor feasibility. In the renal transplantation setting, this particularly applies to living renal transplant donor eligibility screening, renal transplant function monitoring and research purposes. Read More

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The role of cGMP-signalling and calcium-signalling in photoreceptor cell death: perspectives for therapy development.

Pflugers Arch 2021 Apr 16. Epub 2021 Apr 16.

Institute for Ophthalmic Research, University of Tübingen, Elfriede-Aulhorn-Strasse 7, 72076, Tübingen, Germany.

The second messengers, cGMP and Ca, have both been implicated in retinal degeneration; however, it is still unclear which of the two is most relevant for photoreceptor cell death. This problem is exacerbated by the close connections and crosstalk between cGMP-signalling and calcium (Ca)-signalling in photoreceptors. In this review, we summarize key aspects of cGMP-signalling and Ca-signalling relevant for hereditary photoreceptor degeneration. Read More

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A year in pharmacology: new drugs approved by the US Food and Drug Administration in 2020.

Naunyn Schmiedebergs Arch Pharmacol 2021 Apr 16. Epub 2021 Apr 16.

Department of Pharmacology, Johannes Gutenberg University, Langenbeckstr. 1, 55118, Mainz, Germany.

While the COVID-19 pandemic also affected the work of regulatory authorities, the US Food and Drug Administration approved a total of 53 new drugs in 2020, one of the highest numbers in the past decades. Most newly approved drugs related to oncology (34%) and neurology (15%). We discuss these new drugs by level of innovation they provide, i. Read More

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Directed differentiation of human induced pluripotent stem cells to hepatic stellate cells.

Nat Protoc 2021 Apr 16. Epub 2021 Apr 16.

Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

Hepatic stellate cells (HSCs) are nonparenchymal liver cells responsible for extracellular matrix homeostasis and are the main cells involved in the development of liver fibrosis following injury. The lack of reliable sources of HSCs has hence limited the development of complex in vitro systems to model liver diseases and toxicity. Here we describe a protocol to differentiate human induced pluripotent stem cells (iPSCs) into hepatic stellate cells (iPSC-HSCs). Read More

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A cell based assay for evaluating binding and uptake of an antibody using hepatic nonparenchymal cells.

Sci Rep 2021 Apr 16;11(1):8383. Epub 2021 Apr 16.

Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba, Chiba, 260-0856, Japan.

Evaluation of the binding and uptake of an antibody in liver non-parenchymal cells (NPC), including liver sinusoidal endothelial cells, is important for revealing its pharmacokinetic (PK) behavior, since NPC has important roles in eliminating an antibody from the blood via the Fc fragment of IgG receptor IIB (FcγRIIB). However, there is currently no in vitro quantitative assay using NPC. This study reports on the development of a cell-based assay for evaluating the binding and uptake of such an antibody using liver NPC of mice and monkeys. Read More

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Microsecond-timescale MD simulation of EGFR minor mutation predicts the structural flexibility of EGFR kinase core that reflects EGFR inhibitor sensitivity.

NPJ Precis Oncol 2021 Apr 16;5(1):32. Epub 2021 Apr 16.

Div. of Experimental Chemotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 3-8-31, Ariake, Koto-ku, Tokyo, Japan.

Approximately 15-30% of patients with lung cancer harbor mutations in the EGFR gene. Major EGFR mutations (>90% of EGFR-mutated lung cancer) are highly sensitive to EGFR tyrosine kinase inhibitors (TKIs). Many uncommon EGFR mutations have been identified, but little is known regarding their characteristics, activation, and sensitivity to various EGFR-TKIs, including allosteric inhibitors. Read More

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Investigating the Utility of Humanized PXR-CAR-CYP3A4/7 Mouse Model to Assess CYP3A-Mediated Induction.

Drug Metab Dispos 2021 Apr 16. Epub 2021 Apr 16.

Preclinical Development Sciences, ORIC Pharmaceuticals, United States

Clinical induction liability is assessed with human hepatocytes. However, underpredictions in the magnitude of clinical induction have been reported. Unfortunately, in vivo studies in animals do not provide additional insight due to species differences in drug metabolizing enzymes and their regulatory pathways. Read More

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Safety, anti-tumor activity, and biomarker analysis in a phase 1 trial of the once-daily Wee1 inhibitor adavosertib (AZD1775) in patients with advanced solid tumors.

Clin Cancer Res 2021 Apr 16. Epub 2021 Apr 16.

Division of Cancer Treatment and Diagnosis, National Cancer Institute

Purpose: The Wee1 kinase inhibitor adavosertib abrogates cell cycle arrest, leading to cell death. Prior testing of twice-daily adavosertib in patients with advanced solid tumors determined the recommended phase 2 dose (RPh2D). Here, we report results for once-daily adavosertib. Read More

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Targeting adenosine with adenosine deaminase 2 to inhibit growth of solid tumors.

Cancer Res 2021 Apr 16. Epub 2021 Apr 16.

Halozyme Therapeutics, Inc.

Extracellular adenosine in tumors can suppress immune responses and promote tumor growth. Adenosine deaminase 2 (ADA2) converts adenosine into inosine. The role of ADA2 in cancer and whether it can target adenosine for cancer therapy has not been investigated. Read More

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SLFN11 inactivation induces proteotoxic stress and sensitizes cancer cells to ubiquitin activating enzyme inhibitor TAK-243.

Cancer Res 2021 Apr 16. Epub 2021 Apr 16.

Center for Cancer Research, Developmental Therapeutics Branch & Laboratory of Molecular Pharmacology, National Cancer Institute

Schlafen11 (SLFN11) inactivation occurs in approximately 50% of cancer cell lines and in a large fraction of patient tumor samples, which leads to chemoresistance. Therefore, new therapeutic approaches are needed to target SLFN11-deficient cancers. To that effect, we conducted a drug screen with the NCATS mechanistic drug library of 1978 compounds in isogenic SLFN11-knockout (KO) and wild-type (WT) leukemia cell lines. Read More

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Nationwide surveillance of bacterial pathogens isolated from patients with acute uncomplicated cystitis in 2018: Conducted by the Japanese Research Group for Urinary Tract Infections (JRGU).

J Infect Chemother 2021 Apr 13. Epub 2021 Apr 13.

Department of Urology, Hyogo College of Medicine College Hospital, 1-1 Mukogawa-machi, Nishinomiya, 663-8501, Japan; Japanese Research Group for Urinary Tract Infection (JRGU), 1-1 Mukogawa- Machi, Nishinomiya, 663-8501, Japan.

Introduction: The aim of this study was to monitor the development of drug-resistant bacteria isolated from acute uncomplicated cystitis (AUC) and to evaluate methodology of the survey conducted by collecting only clinical data.

Methods: We enrolled female patients at least 16 years of age diagnosed with AUC in 2018. Patient information including age, menopausal status, and results of bacteriological examination were collected and analyzed regardless of bacterial identification, antimicrobial susceptibility testing or extended-spectrum β-lactamase (ESBL) detection method. Read More

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IrGO: Iranian traditional medicine General Ontology and knowledge base.

J Biomed Semantics 2021 Apr 16;12(1). Epub 2021 Apr 16.

Department of Traditional Medicine, School of Persian Medicine, Tehran University of Medical Sciences, Tehran, Iran.

Background: Iranian traditional medicine, also known as Persian Medicine, is a holistic school of medicine with a long prolific history. It describes numerous concepts and the relationships between them. However, no unified language system has been proposed for the concepts of this medicine up to the present time. Read More

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A verified genomic reference sample for assessing performance of cancer panels detecting small variants of low allele frequency.

Genome Biol 2021 Apr 16;22(1):111. Epub 2021 Apr 16.

Division of Bioinformatics and Biostatistics, National Center for Toxicological Research, US Food and Drug Administration, Jefferson, AR, 72079, USA.

Background: Oncopanel genomic testing, which identifies important somatic variants, is increasingly common in medical practice and especially in clinical trials. Currently, there is a paucity of reliable genomic reference samples having a suitably large number of pre-identified variants for properly assessing oncopanel assay analytical quality and performance. The FDA-led Sequencing and Quality Control Phase 2 (SEQC2) consortium analyze ten diverse cancer cell lines individually and their pool, termed Sample A, to develop a reference sample with suitably large numbers of coding positions with known (variant) positives and negatives for properly evaluating oncopanel analytical performance. Read More

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