Objective: In the present study, an attempt has been made for subtractive proteomic analysis approach for novel drug targets in Salmonella enterica subsp. enterica serover Typhi str.CT18 using computational tools.
Methods: Paralogous, redundant and less than 100 amino acid protein sequences were removed by using CD-HIT. Further detection of bacterial proteins which are non-homologous to host and are essential for the survival of pathogens by using BLASTp against host proteome and DEG`s, respectively. Comparative Metabolic pathways analysis was performed to find unique and common metabolic pathways. The non-redundant, non-homologous and essential proteins were BLAST against approved drug targets for drug targets while Psortb and CELLO were used to predict subcellular localization.
Results: There were 4473 protein sequences present in NCBI Database for Salmonella enterica subsp. enterica serover Typhi str. CT18 out of these 327 were essential proteins which were non-homologous to human. Among these essential proteins, 124 proteins were involved in 19 unique metabolic pathways. These proteins were further BLAST against approved drug targets in which 7 cytoplasmic proteins showed druggability and can be used as a therapeutic target.
Conclusion: Drug targets identification is the prime step towards drug discovery. We identified 7 cytoplasmic druggable proteins which are essential for the pathogen survival and non-homologous to human proteome. Further in vitro and in vivo validation is needed for the evaluation of these targets to combat against salmonellosis.
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http://dx.doi.org/10.2174/1568026619666191105102156 | DOI Listing |
Mol Cancer Ther
January 2025
University of Michigan-Ann Arbor, Ann Arbor, MI, United States.
Up to 90% of high-grade serous ovarian cancer (HGSC) patients will develop resistance to platinum-based chemotherapy, posing substantial therapeutic challenges due to a lack of universally druggable targets. Leveraging BenevolentAI's AI-driven approach to target discovery, we screened potential AI-predicted therapeutic targets mapped to unapproved tool compounds in patient-derived 3D models. This identified TNIK, which is modulated by NCB-0846, as a novel target for platinum-resistant HGSC.
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February 2022
Instituto de Investigação E Inovação Em Saúde (i3S), University of Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal.
Osteosarcoma (OS) is the most common primary bone cancer in children and young adults. This type of cancer is characterized by a high mortality rate, especially for patients with resistant lung metastases. Given its low incidence, high genetic heterogeneity, the lack of effective targets, and poor availability of relevant in vitro and in vivo models to study the tumor progression and the metastatic cascade, the pathophysiology of OS is still poorly understood and the translation of novel drugs into the market has become stagnant.
View Article and Find Full Text PDFLife Med
December 2022
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.
In Vitro Model
December 2022
Faculty of Medicine, University of Southampton, Southampton, UK.
Purpose: Alzheimer's disease (AD) early pathology needs better understanding and models. Here, we describe a human induced pluripotent stem cells (iPSCs)-derived 3D neural culture model to study certain aspects of AD biochemistry and pathology.
Method: iPSCs derived from controls and AD patients with Presenilin1 mutations were cultured in a 3D platform with a similar microenvironment to the brain, to differentiate into neurons and astrocytes and self-organise into 3D structures by 3 weeks of differentiation in vitro.
Cureus
December 2024
Neurosurgery, Federal Fluminense University, Niterói, BRA.
The coexistence of type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) represents a significant global health challenge, contributing to substantial morbidity, mortality, and economic burden. T2DM is the leading cause of CKD, and CKD exacerbates diabetes-related complications, creating a bidirectional relationship driven by oxidative stress, inflammation, and endothelial dysfunction. Diabetic kidney disease (DKD), affecting some individuals with T2DM, accelerates progression to end-stage renal disease (ESRD) and increases cardiovascular mortality.
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