Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1200202 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| Other | ||||
| SRR31771064.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 2 of 2 |
Similar Datasets
Project description:The emergence of drug-resistant viruses against nucleot(s)ide analogs (NAs), which are the main treatment for chronic hepatitis B virus (HBV) infection, has become a problem. To discover novel anti-HBV compounds with a low risk of emergence of drug-resistant viruses, we performed screening of a G protein-coupled receptor-associated compound library and identified Rimonabant as a candidate. Transcriptome analysis of Rimonabant-treated primary hepatocytes by RNA sequencing revealed that the transcriptional activity of HNF4α, which is known to stimulate viral RNA synthesis, was depressed.
2020-01-26 | GSE139597 | GEO
Project description:There is a need to discover and develop non-toxic antibiotics that are effective against metabolically dormant bacteria, which underlie chronic infections and promote antibiotic resistance. Traditional antibiotic discovery has historically favored compounds effective against actively metabolizing cells, a property that is not predictive of efficacy in metabolically inactive contexts. Here, we combine a stationary-phase screening method with deep learning-powered virtual screens and toxicity filtering to discover compounds with lethality against metabolically dormant bacteria and favorable toxicity profiles. The most potent and structurally novel compound without any obvious mechanistic liability was semapimod, an anti-inflammatory drug effective against stationary-phase E. coli and A. baumannii. Integrating microbiological assays, biochemical measurements, and single-cell microscopy, we show that semapimod selectively disrupts and permeabilizes the bacterial outer membrane by binding lipopolysaccharide. This work illustrates the value of harnessing non-traditional screening methods and deep learning models to identify non-toxic antibacterial compounds that are effective in infection-relevant contexts.
2023-08-21 | PXD044230 | Pride
Project description:We identified novel nicotinamide-based FLT3 inhibitors ( HSN748) that specifically target FLT3-ITD at sub-nanomolar concentrations and are effective against drug-resistant secondary mutations. In the current study, we evaluated these compounds’ antileukemic activity against FLT3-ITD and gatekeeper mutations in drug-resistant AML, relapsed/refractory AMLs with FLT3 mutations
2024-06-15 | GSE221459 | GEO
Project description:Chemotherapy resistance is considered one of the main causes of tumor relapse, still challenging researchers for the identification of the molecular mechanisms sustaining its emergence. Here, we setup and characterized chemotherapy-resistant models of Medulloblastoma (MB), one of the most lethal pediatric brain tumors, to uncover targetable vulnerabilities associated to their resistant phenotype. Integration of proteomic, transcriptomic and kinomic data revealed a significant deregulation of several pathways in resistant MB cells, converging to cell metabolism, RNA/protein homeostasis, and immune response, eventually impacting on patient outcome. Moreover, resistant MB cell response to a large library of compounds through a high-throughput screening, highlighted nucleoside metabolism as a relevant vulnerability of chemotolerant cells, with peculiar antimetabolites demonstrating increased efficacy against them and even synergism with conventional chemotherapeutics. Our results suggest that drug-resistant cells significantly rewire multiple cellular processes, allowing their adaptation to a chemotoxic environment, nevertheless exposing alternative actionable susceptibilities for their specific targeting. In this study, we generated and characterized from a proteomic, transcriptional and kinomic point of view chemothrapy-resistant MB cells. Integrated data were then associated to the response of MB resistant cells to a large library of compounds through an high throughput screening approach identifying nucleoside metabolism as a peculiar targetable vulnerability emerged after chemotherapy adaptation.
2023-11-22 | GSE220543 | GEO
Project description:Screening of various bisquaternary bisnaphthalimides against a variety of human pathogens revealed one compound, designated MT02, with strong inhibitory effects against gram-positive bacteria. The minimal inhibitory concentrations ranged from 0.31 µg/ml against community-acquired methicillin resistant Staphylococcus aureus (MRSA) strain USA300 to 20 µg/ml against Streptococcus pneumonia. DNA-microarray studies generated a transcriptional signature characterized by a strong increase of genes involved in DNA-metabolism, DNA-replication, SOS-response and transport of positively charged compounds. Radioactive whole cell labeling experiments indicated a strong impact of MT02 on bacterial DNA-replication. Furthermore, surface plasmon resonance and gel retardation experiments demonstrated direct binding of MT02 to DNA in a concentration dependent, reversible and sequence-unspecific manner. The data presented suggest that the bisquaternary bisnaphthalimide MT02 exerts anti-gram-positive activity by binding to DNA and thereby prohibiting appropriate DNA-replication. WT strain exposed to MT02 for 60 minutes in rich medium
2011-01-04 | E-GEOD-23077 | biostudies-arrayexpress
Project description:High-Throughput Screening Strategies for the Identification of Active Compounds against Gut Bacteria
| PRJEB64209 | ENA
Project description:New antifungal drugs are urgently needed due to the currently limited selection, the emergence of drug resistance, and the toxicity of several commonly used drugs. To identify drug leads, we screened small molecules using a Saccharomyces reporter bioassay in which the yeast heterologously expresses Hik1, a group III hybrid histidine kinase (HHK) from Magnaporthe grisea. Group III HHKs are integral in fungal cell physiology, and highly conserved throughout this kingdom; they are absent in mammals, making them an attractive drug target. Our screen identified compounds 13 and 33, which showed robust activity against numerous fungal genera including Candida, Cryptococcus and molds such as Aspergillus and Rhizopus. Drug-resistant Candida from patients were also highly susceptible to compounds 13 and 33. While the compounds do not act directly on HHKs, microarray analysis showed that compound 13 induced transcripts associated with oxidative stress, and compound 33, transcripts linked with heavy metal stress. Both compounds were highly active against Candida biofilm, in vitro and in vivo, and exerted synergy with fluconazole, which was inactive alone. Thus, we identified potent, broad-spectrum antifungal drug leads from a small molecule screen using a high-throughput, yeast reporter bioassay. Two-color experimental design testing the effects of 2 antifungal compounds (13 and 33) after 0, 20, 40 60 min. In the referred publication, the t=20, 40, 60 data was normalized against the t=0 data
2012-04-30 | E-GEOD-35105 | biostudies-arrayexpress