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Efficacy of two FDA-approved drug combination in a mouse model of staphylococcal enterotoxin B-induced shock.

Staphylococcal enterotoxin B (SEB) causes lethal shock by potently stimulating the host immune response. Dexamethasone and N-acetyl cysteine (NAC) are anti-inflammatory and antioxidative drugs, respectively, which can independently modulate immune function. Dexamethasone was previously shown to be effective in preventing SEB-induced shock models only if administered early and in multiple doses for a long duration. In this study, dexamethasone and NAC were used in tandem and protected mice (75%) against SEB-induced lethal shock. Hypothermia and weight loss elicited by SEB were also diminished b

Speed and nature of national comprehensive cancer network updates following food and drug administration approvals & withdrawals.

OBJECTIVE: To characterize the speed and nature of National Comprehensive Cancer Network (NCCN) guideline updates following Food and Drug Administration (FDA) approvals and withdrawals. METHODS: We conducted a retrospective observational study to measure and compare the speed of updates to the NCCN guidelines following FDA cancer approvals and withdrawals between October 2022 and July 2024. We also descriptively analyzed the frequency of specific modifications and levels of recommendations made by the NCCN. RESULTS: Of 91 drug indications analyzed, 83 were newly approved, and eight were with

Approved weight loss drugs for obesity with a thorough emphasis on GLP-1 agonist medications: A systematic review.

BACKGROUND: Obesity is a worldwide health concern linked to cardiometabolic comorbidities such as type 2 diabetes, hypertension, dyslipidemia, and heart disease. The management of obesity using pharmacotherapy, especially with GLP-1 receptor agonists and dual incretin agents, has proven successful not only for weight loss but also for gaining control of the metabolic components of the disease. Thus, it is pertinent to analyse the GLP-1-based anti-obesity medications to examine cardiometabolic efficacy and safety using weight loss, glycemic control, cardiometabolic, gastro-intestinal tolerabili

A Topological and Spatial Analysis of FDA-Approved Drugs, Blood-Brain Barrier Permeants, Natural Products, and Metabolites.

In this study, we present a comprehensive structural analysis of four distinct chemical libraries: FDA-approved drugs, blood-brain barrier (BBB) permeable agents, natural products (UNPDA), and human metabolites. Our multidimensional profiling reveals fundamental divergences in molecular architecture. While synthetic drugs (FDA) and CNS-active agents (BBB) follow continuous, Gaussian-like distributions for carbon hybridization, natural products exhibit biosynthetic quantization, discrete, high-intensity abundance spikes at C19 and C30, corresponding to steroid and triterpene scaffolds. Stereoch

Enhancing bioinformatics engineering by utilizing graph therapeutic properties for clinically approved antitoxin drugs in zoonotic diseases.

Anthrax, a zoonotic disease caused by the bacterium Bacillus anthracis. It primarily affects animals and spreads to humans through direct contact or inhalation. This article examines the correlations between physicochemical properties and topological indices of the chemical structures of drugs used to mitigate anthrax disease. This study considers the clinically approved drugs, including ciprofloxacin, levaquin, doryx, penicillin tetrapropyl, and pfizerpen, etc. For the chemical structures of these drugs, we have calculated M-polynomials of various reverse topological indices, including the re

Systemic activation of NRF2 contributes to the therapeutic efficacy of clinically-approved KRAS-G12C anti-cancer drugs.

BACKGROUND: The development and clinical success of KRASG12C inhibitors was a landmark achievement in anti-cancer drug development, as oncogenic KRAS had long been considered an intractable therapeutic target. Patients with KRAS mutant lung cancers frequently present with co-mutations in the KEAP1-NRF2 pathway, and because genetic activation of NRF2 results in resistance to all current anti-cancer therapies, we were motivated to explore how aberrant activation of NRF2 impacts the clinical response to KRASG12C inhibitors. METHODS: A broad range of techniques, including genetic knockouts, scRNA

Non-Catalytic Inhibitors of the p38/MK2 Interface: Repurposing Approved Drugs to Target Neuroinflammation in Alzheimer's Disease.

Neuroinflammation is a key driver of Alzheimer's disease and an emerging therapeutic target. The p38/MK2 pathway regulates microglial cytokine production, yet previous attempts have not yielded modulators with clinically suitable properties. Here, we apply an integrative structure-guided and screening strategy to identify small-molecule disruptors of the p38/MK2 protein-protein interaction (PPI). Virtual screening of FDA-approved drugs prioritized nilotinib, a BCR-ABL inhibitor, as a putative PPI disruptor. Biochemical and molecular dynamics analyses confirmed that nilotinib binds to p38, bloc

Cefepime-enmetazobactam: first approved cefepime-β- lactamase inhibitor combination for multi-drug resistant Enterobacterales.

Cefepime-enmetazobactam is a β-lactam/β-lactamase inhibitor (BL/BLI) combination that has demonstrated potent activity against extended spectrum beta-lactamase (ESBL)-producing Enterobacterales, recently approved by the US FDA for the treatment of complicated urinary tract infections (cUTI) and by the European Medicines Agency and the UK Healthcare products Regulatory Agency for the treatment of cUTI, hospital-acquired pneumonia including ventilator-associated pneumonia and bacteremia in adults. Cefepime is a 4th generation cephalosporin with a broad spectrum bactericidal activity and enhanced

Screening FDA-Approved Oncology Drugs with Three-Dimensional Spheroids Identifies Romidepsin as a Therapeutic Candidate for Osteosarcoma.

UNLABELLED: Osteosarcoma is the most common primary malignant bone tumor and predominantly affects adolescents and young adults. It is the third most common cause of cancer-related deaths among 9 to 24 year olds. Despite aggressive chemotherapeutic and surgical therapies, the survival rate is only 25% for patients with detectable lung metastases at diagnosis and only 70% in patients who present without detectable lung metastases. The poor prognosis is due to growth of metastases irrespective of whether they are initially large enough to detect clinically. It is therefore necessary to develop n

In silico screening and molecular dynamic simulations of FDA-approved drugs as an inhibitor of trypanothione reductase of Leishmania donovani.

Visceral leishmaniasis (VL) is mainly caused by Leishmania donovani (Ld) and Leishmania (L.) infantum, and it is prevalent in Brazil, India and East Africa. VL is a serious health issue, affecting millions of people worldwide and causing thousands of deaths annually. The current treatments for leishmaniasis are inadequate because of their low efficacy, toxicity and growing resistance, underscoring the pressing need to explore new drugs. Among the various molecular targets explored, trypanothione reductase (TR) is of special relevance because of its crucial function in regulating the parasite's

Repurposing of FDA-approved drugs against oligomerization domain of dengue virus NS1 protein: a computational approach.

Dengue fever is a serious health hazard on a global scale and its primary causative agent is the dengue virus (DENV). The non-structural protein 1 (NS1) of DENV plays a pivotal role in pathogenesis. It is associated with several autoimmune events, endothelial cell apoptosis, and vascular leakage, which increase mainly during the critical phase of infection. In this study, important residues of the oligomerization domain of NS1 protein were identified by literature searches. Virtual screening has been conducted using the entire dataset of the DrugBank database and the potential small-molecule i

A New Beginning to the Existing Medicines; Repurposing FDA-Approved Drugs for the Neglected Re-Emerging Disease Leptospirosis.

Leptospirosis is one of the re-emerging zoonotic diseases, especially in tropical regions. Many antibiotics are used to treat leptospirosis, but there are no scientific evidence-based guidelines or systematic clinical trials for using these drugs. A bioinformatics approach was made to shortlist some Food and Drug Administration (FDA) of the United States of America-approved and currently used drugs for leptospirosis. The existing drugs from the Drug Bank database, which are currently not used for leptospirosis, were selected to identify their target proteins and binding sites using bioinformat

The evidence base of US Food and Drug Administration approvals of novel cancer therapies from 2000 to 2020.

Concerns have been raised that regulatory programs to accelerate approval of cancer drugs in cancer may increase uncertainty about benefits and harms for survival and quality of life (QoL). We analyzed all pivotal clinical trials and all non-pivotal randomized controlled trials (RCTs) for all cancer drugs approved for the first time by the FDA between 2000 and 2020. We report regulatory and trial characteristics. Effects on overall survival (OS), progression-free survival and tumor response were summarized in meta-analyses. Effects on QoL were qualitatively summarized. Between 2000 and 2020, t

FDA-Approved Small Molecule Compounds as Drugs for Solid Cancers from Early 2011 to the End of 2021.

Solid cancers are the most common types of cancers diagnosed globally and comprise a large number of deaths each year. The main challenge cu … 4 new small molecule agents were introduced each year, with a few exceptions, for a total of 62 new drug approvals. A total of 50 of all FDA-approved drugs have also been authorized for use in the European Union by the European Medicines Agency (EMA). Our analysis indicates that many more anticancer molecules show a selective mode of action, i.e., 49 targeted a …

Cost-effectiveness evidence on approved cancer drugs in Ireland: the limits of data availability and implications for public accountability.

BackgroundWe surveyed evidence published by Ireland's National Centre for Pharmacoeconomics (NCPE) on the cost-effectiveness of cancer drugs approved for funding within the Irish public healthcare system. The purpose is threefold: to assess the completeness and clarity of publicly available cost-effectiveness data of such therapies; to provide summary estimates of that data; to consider the implications of constraints on data availability for accountability regarding healthcare resource allocation.MethodsThe National Cancer Control Programme lists 91 drug-indication pairs approved between June

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… In some cases a single drug approval record on the NCCP website corresponds to multiple indications. We considered each pair separately unless the relevant NCPE HTA summary aggregated the cost-effectiveness of the indications together. … While of course some drugs may achieve complete remission in some patients, we believe it important the public appreciate that new cancer drugs approved in Ireland over nearly a decade will provide a mean of 0.85 QALYs; less than 1 year equivalent of good health. …

Discovery of SARS-CoV-2 antiviral synergy between remdesivir and approved drugs in human lung cells.

SARS coronavirus 2 (SARS-CoV-2) has caused an ongoing global pandemic with significant mortality and morbidity. At this time, the only FDA-approved therapeutic for COVID-19 is remdesivir, a broad-spectrum antiviral nucleoside analog. Efficacy is only moderate, and improved treatment strategies are urgently needed. To accomplish this goal, we devised a strategy to identify compounds that act synergistically with remdesivir in preventing SARS-CoV-2 replication. We conducted combinatorial high-throughput screening in the presence of submaximal remdesivir concentrations, using a human lung epithel

Phenotypic screening of 1,953 FDA-approved drugs reveals 26 hits with potential for repurposing for Peyronie's disease.

Drug repurposing has been shown to bring safe medications to new patient populations, as recently evidenced by the COVID-19 pandemic. We investigated whether we could use phenotypic screening to repurpose drugs for the treatment of Peyronie's disease (PD). PD is a fibrotic disease characterised by continued myofibroblast presence and activity leading to formation of a plaque in the penile tunica albuginea (TA) that can cause pain during erection, erectile dysfunction, and penile deformity. PD affects 3-9% of men with treatment options limited to surgery or injection of collagenase which can on

Regulatory and clinical consequences of negative confirmatory trials of accelerated approval cancer drugs: retrospective observational study.

OBJECTIVES: To investigate the regulatory handling of cancer drugs that were granted accelerated approval by the US Food and Drug Administration (FDA) but failed to improve the primary endpoint in post-approval trials and to evaluate the extent to which negative post-approval trials changed the recommendations in treatment guidelines. DESIGN: Retrospective observational study. SETTING: FDA and National Comprehensive Cancer Network (NCCN) reports. INCLUDED DRUGS: Cancer drugs that received accelerated approval from the FDA and had negative post-approval trials. MAIN OUTCOME MEASURES: Regula