Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA219717 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Identification and Validation of Small Molecule Inhibitors Targeting FGFR through Molecular Docking-Based Screening
| PRJNA1113567 | ENA
Project description:We developed a general approach to small molecule library screening called GE-HTS (Gene Expression-Based High Throughput Screening) in which a gene expression signature is used as a surrogate for cellular states and applied it to the identification of compounds inducing the differentiation of acute myeloid leukemia cells. In screening 1,739 compounds, we identified 8 that reliably induced the differentiation signature, and furthermore yielded functional evidence of bona fide differentiation. This SuperSeries is composed of the following subset Series:; GSE976: Gene Expression-Based High Throughput Screening: APL Treatment with Candidate Compounds; GSE982: Gene Expression-Based High Throughput Screening: HL-60 Cell Treatment with Candidate Compounds; GSE983: Gene Expression-Based High Throughput Screening: Primary Patient AML Blasts, Normal Neutrophils, and Normal Monocytes; GSE985: Gene Expression-Based High Throughput Screening: HL-60 Cells Treated with ATRA and PMA Experiment Overall Design: Refer to individual Series
2007-09-20 | E-GEOD-995 | biostudies-arrayexpress
Project description:We developed a general approach to small molecule library screening called GE-HTS (Gene Expression-Based High Throughput Screening) in which a gene expression signature is used as a surrogate for cellular states and applied it to the identification of compounds inducing the differentiation of acute myeloid leukemia cells. In screening 1,739 compounds, we identified 8 that reliably induced the differentiation signature, and furthermore yielded functional evidence of bona fide differentiation. This SuperSeries is composed of the SubSeries listed below.
2004-01-30 | GSE995 | GEO
Project description:High-throughput small molecule screen identifies inhibitors of aberrant chromatin accessibility
| PRJNA261972 | ENA
Project description:Targeting aberrant epigenetic programs that drive tumorigenesis is a promising approach to cancer therapy. DNA-encoded small-molecule library (DEL) screening is a core platform technology increasingly used to identify drugs that bind to protein targets. Here, we use DEL screening against bromodomain and extra-terminal motif (BET) proteins to identify inhibitors with new chemotypes, and successfully identified BBC1115 as a selective BET inhibitor. While BBC1115 does not structurally resemble OTX-015, a clinically active pan-BET inhibitor, our intensive computational modeling and biological characterization revealed that BBC1115 binds to BET protein BRD4 and suppresses aberrant cell fate programs. Phenotypically, BBC1115-mediated BET inhibition impaired proliferation in acute myeloid leukemia, pancreatic, and colorectal cancer cells in vitro. Moreover, intravenous administration of BBC1115 inhibited subcutaneous pancreatic and colorectal cancer xenograft growth with minimal toxicity and favorable pharmacokinetic properties in vivo. Since epigenetic regulations are ubiquitously employed across normal and malignant cells, it will be critical to evaluate whether BBC1115 interferes with normal cellular functions. Nonetheless, our study implicates that integrating DEL-based small-molecule compound screening and multi-step biological validation represents a reliable strategy to discover new chemotypes with selectivity, efficacy, and safety profiles for targeting proteins involved in epigenetic regulation in human malignancies.
2023-02-16 | GSE225342 | GEO
Project description:Targeting aberrant epigenetic programs that drive tumorigenesis is a promising approach to cancer therapy. DNA-encoded small-molecule library (DEL) screening is a core platform technology increasingly used to identify drugs that bind to protein targets. Here, we use DEL screening against bromodomain and extra-terminal motif (BET) proteins to identify inhibitors with new chemotypes, and successfully identified BBC1115 as a selective BET inhibitor. While BBC1115 does not structurally resemble OTX-015, a clinically active pan-BET inhibitor, our intensive computational modeling and biological characterization revealed that BBC1115 binds to BET protein BRD4 and suppresses aberrant cell fate programs. Phenotypically, BBC1115-mediated BET inhibition impaired proliferation in acute myeloid leukemia, pancreatic, and colorectal cancer cells in vitro. Moreover, intravenous administration of BBC1115 inhibited subcutaneous pancreatic and colorectal cancer xenograft growth with minimal toxicity and favorable pharmacokinetic properties in vivo. Since epigenetic regulations are ubiquitously employed across normal and malignant cells, it will be critical to evaluate whether BBC1115 interferes with normal cellular functions. Nonetheless, our study implicates that integrating DEL-based small-molecule compound screening and multi-step biological validation represents a reliable strategy to discover new chemotypes with selectivity, efficacy, and safety profiles for targeting proteins involved in epigenetic regulation in human malignancies.
2023-02-16 | GSE225339 | GEO
Project description:Generation of murine stem cells by small molecule
| PRJNA203557 | ENA
Project description:Small-Molecule PAPD5 Inhibitors Restore Telomerase Activity in Patient Stem Cells
| PRJNA605628 | ENA
Project description:Disruption of alternative splicing frequently causes or contributes to human diseases and disorders. Consequently, there is a need for efficient and sensitive reporter assays capable of screening chemical libraries for compounds with efficacy in modulating important splicing events. Here, we describe a screening workflow employing dual Nano and Firefly luciferase alternative splicing reporters that affords highly efficient, sensitive, and linear detection of small molecule responses. Applying this system to a screen of ~95,000 small molecules, we identify compounds that selectively activate or repress a neuronal microexon network that is frequently disrupted in autism and overexpressed in neuroendocrine cancers. Remarkably, among the most potent and selective activating compounds are histone deacetylase (HDAC) inhibitors. We thus describe a high-throughput screening system for candidate splicing therapeutics, a resource of small molecule modulators of microexons, and insight into the mode of action and potential utility of HDAC inhibitors in the context of neurological disorders.
2024-05-28 | GSE228599 | GEO
Project description:Small molecule inhibitors of glycosylation enzymes are valuable tools for dissecting glycan functions and potential drug candidates. Screening for inhibitors of glycosyltransferases are mainly performed by in vitro enzyme assays with difficulties moving candidates to cells and animals. Here, we circumvent this by employing a cell-based screening assay using glycoengineered cells expressing tailored reporter glycoproteins. We focused on GalNAc-type O-glycosylation, and selected the GalNAc-T11 isoenzyme that selectively glycosylates the endocytic low density lipoprotein receptor (LDLR)-related proteins as target. Our screen of a limited small molecule compound library did not identify selective inhibitors of GalNAc-T11, however we identified two compounds that broadly inhibited Golgi-localized glycosylation processes. These compounds mediated reversible fragmentation of the Golgi system without affecting secretion. We demonstrate how these inhibitors can be used to manipulate glycosylation in cells to induce expression of truncated O-glycans and augment binding of cancer-specific Tn-glycoprotein antibodies and to inhibit expression of heparan sulfate and binding and infection of SARS-CoV-2.
2023-05-05 | PXD039334 | Pride