Drug repurposing is preferred over de-novo drug discovery to unveil the therapeutic applications of existing drug candidates before investing considerable resources in unexplored novel chemical entities. This study demonstrated multifaceted stratagems to reconnoiter promising repurposable candidates against Hepatocellular Carcinoma (HCC) by amalgamating Real-World-Data (RWD) with bioinformatics algorithms corroborated with and studies. At the outset, the RWD from the Food and Drug Administration Adverse Event Reporting System (FAERS) was explored to navigate signals to retrieve repurposable drugs that are inversely associated with HCC via Disproportionality Analysis.
View Article and Find Full Text PDFThe conventional theory linking a single gene with a particular disease and a specific drug contributes to the dwindling success rates of traditional drug discovery. This requires a substantial shift focussing on contemporary drug design or drug repurposing, which entails linking multiple genes to diverse physiological or pathological pathways and drugs. Lately, drug repurposing, the art of discovering new/unlabelled indications for existing drugs or candidates in clinical trials, is gaining attention owing to its success rates.
View Article and Find Full Text PDFOral cancer is one of the 19most rapidly progressing cancers associated with significant mortality, owing to its extreme degree of invasiveness and aggressive inclination. The early occurrences of this cancer can be clinically deceiving leading to a poor overall survival rate. The primary concerns from a clinical perspective include delayed diagnosis, rapid disease progression, resistance to various chemotherapeutic regimens, and aggressive metastasis, which collectively pose a substantial threat to prognosis.
View Article and Find Full Text PDFThe clinical management of oral cancer is often frequented with challenges that arise from relapse, recurrence, invasion and resistance towards the cornerstone chemo and radiation therapies. The recent conceptual advancement in oncology has substantiated the role of cancer stem cells (CSC) as a predominant player of these intricacies. CSC are a sub-group of tumor population with inherent adroitness to self-renew with high plasticity.
View Article and Find Full Text PDFTyrosine Kinase beta (TRKβ), is a type I membrane receptor which plays a major role in various signalling pathways. TRKβ was found to be upregulated in various cancers and contrastingly downregulated in various neurodegenerative disorders. Hitherto, contemporary drug research is oriented towards discovery of TRKβ inhibitors, thus neglecting the development of TRKβ agonists.
View Article and Find Full Text PDFBackground And Objectives: Alzheimer's Disease (AD), an extremely progressive neurodegenerative disorder is an amalgamation of numerous intricate pathological networks. This century old disease is still an unmet medical condition owing to the modest efficacy of existing therapeutic agents in antagonizing the multi-targeted pathological pathways underlying AD. Given the paucity in AD specific drugs, fabricating comprehensive research strategies to envision disease specific targets to channelize and expedite drug discovery are mandated.
View Article and Find Full Text PDFHepatocellular carcinoma (HCC) is the fifth most common neoplasm in the world. Chronic inflammation of liver and associated wound healing processes collectively contribute to the development of cirrhosis which further progresses to dysplastic nodule and then to HCC. Etiological mediators and ongoing manipulations at cellular level in HCC are well established; however, key protein interactions and genetic alterations involved in stepwise hepatocarcinogenic pathways are seldom explored.
View Article and Find Full Text PDFAlzheimer's disease (AD), a dreadful neurodegenerative disorder that affects cognitive and behavioral function in geriatric populations, is characterized by the presence of amyloid deposits and neurofibrillary tangles in brain regions. The International D World Alzheimer Report 2018 noted a global prevalence of 50 million AD cases and forecasted a threefold rise to 139 million by 2050. Although there exist numerous genetic association studies pertinent to AD in different ethnicities, critical genetic factors and signaling pathways underlying its pathogenesis remain ambiguous.
View Article and Find Full Text PDFDrug discovery for Alzheimer's Disease (AD) is channeled towards unravelling key disease specific drug targets/genes to predict promising therapeutic candidates. Though enormous literature on AD genetics is available, there exists dearth in data pertinent to drug targets and crucial pathological pathways intertwined in disease progression. Further, the research findings revealing genetic associations failed to demonstrate consistency across different studies.
View Article and Find Full Text PDFAt present, schizophrenia guidelines recommend waiting for 8 weeks before considering a patient as non-responder. This study aims to detect the optimal early response threshold that best predict the final outcome of olanzapine. The study was conducted for 8-week, four points follow up (week 2,3,4, and 8) prospective observational study.
View Article and Find Full Text PDFAlzheimer's disease (AD), a most prevailing neurodegenerative disorder with turbulence in cognitive and behavioural abilities, epitomizes one of the highest unmet medical requirements. The current AD treatment focuses merely on symptomatic relief, this explains a dearth in drug research oriented towards unwinding of disease specific druggable targets. On the other hand, toxicity and poor bioavailability hamper the evolution of novel chemical entities (NCE) in clinical trials.
View Article and Find Full Text PDFBackground: In current clinical practice, regardless of the clinical guidelines, BZDs and Z drugs are used beyond the period of indication, resulting in undesirable effects. This study aimed to assess feasibility of deprescribing amongst patients utilizing BZDs and Z drugs inappropriately for longer duration than the prescribed period. The study also analysed the Quality of Sleep (QoS) and Cost Savings incurred amongst deprescribed patients.
View Article and Find Full Text PDFDrug Res (Stuttg)
February 2019
In this study, the optimized 4-(4-hydroxybenzyl)-2-amino-6-hydroxypyrimidine-5-carboxamide derivative was formulated as nanoparticles to evaluate for their anticancer activity. The response surface methodology (RSM) was performed with utilization of Box-Behnken statistical design (BBSD) to optimize the experimental conditions for identification of significant synthetic methodology. To explore the stability of the derivative was done by density functional theory (DFT).
View Article and Find Full Text PDFBackground: Psychotropic medications are the mainstay of treatment in psychiatric disorders and are associated with ADRs which affect the compliance and treatment course. Previous studies have looked at the frequency, profile of ADRs and their management aspects. However, the systematic comparison between IP and OP was lacking even though there is a prescription pattern difference.
View Article and Find Full Text PDF