Результаты поиска

A Cell-Based Renilla Luminescence Reporter Plasmid Assay for High-Throughput Screening to Identify Novel FDA-Approved Drug Inhibitors of HPV-16 Infection.

Like cervical cancer, anal cancer is caused by human papillomavirus (HPV). HPV is the most common sexually transmitted agent and is found in the anal canal of almost all HIV-positive men who have sex with men (MSM). Rates of HPV anal cancer are disproportionately higher in this population. Although the nanovalent HPV vaccine is efficacious in protecting against oncogenic HPV types, a substantial proportion of MSM remains unvaccinated and anal HPV infection continues to be an important public health burden. Therefore, it is important to identify strategies to prevent HPV infection. We report on

A Food and Drug Administration-Approved Antiviral Agent that Inhibits Adenylyl Cyclase Type 5 Protects the Ischemic Heart Even When Administered after Reperfusion.

A Food and Drug Administration-approved antiviral agent, known as vidarabine or adenine 9-β-D-arabinofuranoside (AraA), has features of inhibiting adenylyl cyclase type 5 (AC5) and protects against chronic coronary artery occlusion (CAO). The goal of this investigation was to determine whether AraA protects against myocardial ischemia, even when delivered after coronary artery reperfusion (CAR). AraA, delivered after CAR in wild-type mice, reduced infarct size by 55% compared with vehicle-treated controls, whereas an equal dose of adenosine reduced infarct size only when administered before CA

Opioid drugs in maintenance and detoxification treatment of opiate addiction; addition of buprenorphine and buprenorphine combination to list of approved opioid treatment medications. Interim final rule.

This interim final rule amends the Federal opioid treatment program regulations by adding buprenorphine and buprenorphine combination products to the list of approved opioid treatment medications that may be used in federally certified and registered opioid treatment programs. The Food and Drug Administration (FDA) recently approved Subutex[reg] (buprenorphine) and Suboxone[reg] (buprenorphine in fixed combination with naloxone) for the treatment of opiate dependence. These two products will join methadone and ORLAAM[reg] as medications that may be used in opioid treatment programs for the mai

An In Silico Design, Simulation, Virtual Screening, and Evaluation of Natural Products as Inhibitors of Breast Cancer-Causing Kallikrein11 Protein and Comparison of Binding Affinities with Approved Drugs.

INTRODUCTION: The current study aims to determine the structure of the protein Kallikrein 11 and to screen for small natural product ligands to identify inhibitors of Kallikrein 11. Kallikreinrelated peptidase 11 (KLK 11) belongs to the Kallikrein family of Serine proteases. Kallikrein 11 is a multifunctional protease. In addition to causing cancer, this plays a critical role in a variety of physiological functions, including blood pressure regulation, sperm liquefaction, and skin desquamation. This study aims to identify the protein's 3D structure, perform virtual screening with a natural pro

Repurposing FDA-Approved Antiviral Drugs Ganciclovir and Acyclovir Against Respiratory Syncytial Virus Nucleoprotein: Molecular Docking, ADMET, PASS, and Molecular Dynamics Simulations.

Respiratory syncytial virus (RSV) is a prevalent viral respiratory infection that has been increasingly affecting children under 5 years old globally. Although RSV can infect individuals of all ages, certain groups are at higher risk, particularly infants and young children. This growing concern underscores the urgent need for effective therapeutic options. In this context, drug repurposing emerges as a promising strategy, allowing existing medications to be utilized for new therapeutic applications beyond their original indications. In this research, we utilized library of FDA-approved antivi

Specificity of Food and Drug Administration postmarketing requirements and associations with timely submissions and regulatory decisions for oncology accelerated approvals, 2011-2023: a cross-sectional analysis.

OBJECTIVES: To assess the specificity of postmarketing requirement (PMR) statements and associations between PMR statement specificity and PMR study characteristics, timeliness and regulatory decisions. METHODS AND ANALYSIS: This was a cross-sectional analysis of publicly available Food and Drug Administration (FDA) databases to characterise PMR statements for oncology accelerated approvals (AAs) between January 2011 and July 2023. Characteristics of trials supporting AA and PMR studies were identified from product labels on the Drugs@FDA database and ClinicalTrials.gov. Main outcomes and mea

Pathogenesis of COVID19 and the applications of US FDA-approved repurposed antiviral drugs to combat SARS-CoV-2 in Saudi Arabia: A recent update by review of literature.

Still, there is no cure for the highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-caused coronavirus disease 2019 (COVID19). The COVID19 pandemic caused health emergencies which resulted in enormous medical and financial consequences worldwide including Saudi Arabia. Saudi Arabia is the largest Arab country of the Middle East. The urban setting of Saudi Arabia makes it vulnerable towards SARS-CoV-2 (SCV-2). Religious areas of this country are visited by millions of pilgrims every year for the Umrah and Hajj pilgrimage, which contributes to the potential COVID19 epi

Computational screening and MM/GBSA-based MD simulation studies reveal the high binding potential of FDA-approved drugs against Cutibacterium acnes sialidase.

Cutibacterium acnes is an opportunistic pathogen linked with acne vulgaris, affecting 80-90% of teenagers globally. On the leukocyte (WBCs) cell surface, the cell wall anchored sialidase in C. acnes virulence factor, catalysing the sialoconjugates into sialic acids and nutrients for C. acnes resulting in human skin inflammation. The clinical use of antibiotics for acne treatments has severe adverse effects, including microbial dysbiosis and resistance. Therefore, identifying inhibitors for primary virulence factors (Sialidase) was done using molecular docking of 1030 FDA-approved drugs. Initia

A simple but novel glycymicelle ophthalmic solution based on two approved drugs empagliflozin and glycyrrhizin: in vitro/in vivo experimental evaluation for the treatment of corneal alkali burns.

A simple but novel ophthalmic solution based on two approved drugs was developed to reposition existing drugs to treat new diseases. This nanoformulation was developed using the phytochemical drug glycyrrhizin as an amphiphilic nanocarrier to micellarly solubilize empagliflozin (EMP), an oral drug that is widely used to control high blood glucose but has poor water solubility. This novel nanoformulation, which we designated the EMP@glycymicelle ophthalmic solution, was obtained using a simple preparation process. The resulting solution was a clear solution with an EMP encapsulation efficiency

A novel cell-based assay for the high-throughput screening of epithelial-mesenchymal transition inhibitors: Identification of approved and investigational drugs that inhibit epithelial-mesenchymal transition.

OBJECTIVES: Lung cancer with distant metastases is associated with a very poor prognosis, and epithelial-mesenchymal transition (EMT) contributes to cancer metastasis. Therefore, elucidation and inhibition of EMT signaling in lung cancer may be a new therapeutic strategy for improving the prognosis of patients. We constructed a high-throughput screening system for EMT inhibitors. Using this system, we aimed to identify compounds that indeed inhibit EMT. MATERIALS AND METHODS: We generated a luciferase reporter cell line using A549 human lung cancer cells and E-cadherin or vimentin as EMT mark

Anti-Fungal Potential of Structurally Diverse FDA-Approved Therapeutics Targeting Secreted Aspartyl Proteinase (SAP) of Candida albicans: an In Silico Drug Repurposing Approach.

In recent years, candidiasis attains major clinical importance due to its unique pathogenic strategy, which distinguishes it from other nosocomial infections. Secreted aspartyl proteinases (SAPs) is a hydrolytic enzyme secreted by Candida species that mediate versatile biological activity including hyphal formation, adherence, biofilm formation, phenotypic adaptation, etc. Emerging clinical evidence strongly suggested that conventional anti-fungal agent's are often prone to high level of resistance upon repeated exposure. Drug repurposing is an ideal strategy that shall impose the additional c

Repurposing potential of FDA-approved and investigational drugs for COVID-19 targeting SARS-CoV-2 spike and main protease and validation by machine learning algorithm.

The present study aimed to assess the repurposing potential of existing antiviral drug candidates (FDA-approved and investigational) against SARS-CoV-2 target proteins that facilitates viral entry and replication into the host body. To evaluate molecular affinities between antiviral drug candidates and SARS-CoV-2 associated target proteins such as spike protein (S) and main protease (Mpro ), a molecular interaction simulation was performed by docking software (MVD) and subsequently the applicability score was calculated by machine learning algorithm. Furthermore, the STITCH algorithm was used

Prediction of novel inhibitors for Crotalus adamanteus l-amino acid oxidase by repurposing FDA-approved drugs: a virtual screening and molecular dynamics simulation investigation.

One of the deadliest enzymes in the snake venom is l-amino acid oxidase (LAAO) which plays an important role in the pathophysiological effects during snake envenomation. Some effects of this enzyme on the human body are apoptosis, platelet aggregation, edema, hemorrhage, and cytotoxicity. Hence, inhibiting the enzyme activity to reduce its degradation effects is of great medical and pharmacological importance. On the other hand, drug repurposing is a process to find the new existing drug for a new medical indication. Since Crotalus adamanteus LAAO has no crystal structure in the protein data b

Measurable residual disease (MRD) as a surrogate end point for clinical drug approval in acute myeloid leukemia (AML): Perspectives from the MRD Partnership and Alliance in AML Clinical Treatment Consortium.

Despite advances in acute myeloid leukemia (AML) treatment, significant unmet medical needs remain. Surrogate end points for overall survival can accelerate the approval of novel therapies. Measurable residual disease (MRD) is a promising surrogate end point candidate, providing a sensitive and quantitative assessment of disease burden. Numerous studies have demonstrated that negative MRD status-across diverse methodologies, assessment timepoints and thresholds, patient subgroups, and clinical settings-independently predicts improved survival. Although MRD can inform therapeutic decisions at t

Совпадение в полном тексте источника
… approvals. … Measurable residual disease (MRD) as a surrogate end point for clinical drug approval in acute myeloid leukemia (AML): perspectives from the MRD Partnership and Alliance in AML Clinical Treatment Consortium. …

Comparison of treatment efficacy of targeted therapies approved in China for non-small cell lung cancer before and after the introduction of accelerated drug marketing registration procedures.

INTRODUCTION: The introduction of Accelerated Drug Marketing Registration Procedures (ADMRPs) in China has improved patient access to innovative therapies, but concerns remain about the robustness and consistency of efficacy evidence. AIM: This study aimed to compare the treatment efficacy of approved targeted therapies for non-small cell lung cancer (NSCLC) before and after the implementation of ADMRPs. METHOD: In this retrospective study, we analyzed targeted therapies for NSCLC approved in China as of December 31, 2024. Approvals were categorized as pre-policy or post-policy groups based

Inhibition of the oncogenic GTPase dynamin-related protein 1 (DRP1) by the FDA-approved drug fosaprepitant: In silico, biophysical, and in vitro characterization of its anti-myeloma activity.

Mitochondrial fission plays a crucial role in sustaining cellular homeostasis, and disturbances in this process have been linked to numerous pathological conditions, including cancer. The central regulator of mitochondrial division is the large GTPase dynamin-related protein 1 (DRP1), whose enzymatic activity drives the constriction and separation of mitochondria. Given its pivotal function, DRP1 has gained attention as a potential oncogenic target across several cancer types. However, the availability of small-molecule inhibitors targeting DRP1 remains limited. To discover novel inhibitors, w

Real-world evidence supporting orphan drugs approvals for rare neuromuscular disorders in the European Union and the United States: Review of public assessment reports (2015-2025).

Real-world data (RWD) and real-world evidence (RWE) are becoming essential complements to conventional clinical trials for drug assessment, particularly for rare neuromuscular disorders where small patient populations heighten outcome uncertainty. Robust RWE could reduce that uncertainty and inform regulatory decisions on orphan drugs (ODs). To review how the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) have incorporated RWE into OD approvals for neuromuscular diseases from January 2015 to January 2025. We reviewed all publicly available EMA European Public Ass

Clinical benefit, reimbursement outcomes, and prices of FDA-approved cancer drugs reviewed through Project Orbis in the USA, Canada, England, and Scotland: a retrospective, comparative analysis.

BACKGROUND: Project Orbis is a global initiative that aims to streamline regulatory review processes across international regulators in the USA, Canada, Australia, UK, Israel, Brazil, Singapore, and Switzerland to bring promising cancer drugs to patients earlier. We explored the clinical benefit, time to regulatory approval and health technology assessment recommendations, reimbursement outcomes, and monthly treatment prices of cancer drugs reviewed through this initiative. METHODS: For this retrospective, comparative analysis, we identified cancer drug approvals reviewed through Project Orbi…