Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

CRISPR screen of genes encoding protein interactors of MCB-613 in parental and EGFR inhibitor resistant EGFR-mutant NSCLC cell lines

ABSTRACT: CRISPR screen of genes encoding protein interactors of MCB-613 in PC9, GR4, and WZR12 cells

ORGANISM(S): Homo sapiens

PROVIDER: GSE262214 | GEO | 2025/12/07

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Gene expression profiling of parental and EGFR inhibitor resistant EGFR-mutant NSCLC cell lines treated with MCB-613

Project description:RNA-seq analysis in PC9, GR4, and WZR12 cells treated with DMSO or MCB-613 for 24 hours.

2025-12-07 | GSE262212 | GEO

CRISPR screen of genes encoding protein interactors of MCB-613 in parental and EGFR inhibitor resistant EGFR-mutant NSCLC cell lines

Project description:CRISPR screen of genes encoding protein interactors of MCB-613 in parental and EGFR inhibitor resistant EGFR-mutant NSCLC cell lines

| PRJNA1090830 | ENA

A Steroid Receptor Coactivator Stimulator (MCB-613) Prevents Adverse Remodeling After Myocardial Infarction

Project description:A Steroid Receptor Coactivator Stimulator (MCB-613) Prevents Adverse Remodeling After Myocardial Infarction

2020-09-06 | GSE157542 | GEO

Gene expression profiling of parental and EGFR inhibitor resistant EGFR-mutant NSCLC cell lines treated with MCB-613

Project description:Gene expression profiling of parental and EGFR inhibitor resistant EGFR-mutant NSCLC cell lines treated with MCB-613

| PRJNA1090829 | ENA

A Steroid Receptor Coactivator Stimulator (MCB-613) Prevents Adverse Remodeling After Myocardial Infarction

Project description:A Steroid Receptor Coactivator Stimulator (MCB-613) Prevents Adverse Remodeling After Myocardial Infarction

| PRJNA661664 | ENA

EGFR inhibitor-resistant lung cancers exhibit collateral sensitivity to a covalent, cysteine-independentKEAP1 oligomerizing molecular bridge

Project description:Targeted therapies have revolutionized cancer care. Unfortunately, most patients develop refractory, multifocal resistance to these therapies within a matter of months. Here, we demonstrate that the evolution of resistance to EGFR inhibitors in EGFR-mutant non-small cell lung cancer endows cells with hypersensitivity to a small molecule compound, MCB-613. Systematic proteomic, functional genomic, and biochemical studies revealed that MCB-613 binds KEAP1 in a covalent, cysteine-independent fashion, acting as a divalent molecular bridge that relies upon lysine residues in the KEAP1 dimerization domain to join monomers of KEAP1 together. Oligomerization of KEAP1 by MCB-613 sets into motion a fatal cascade of KEAP1 dysfunction, ROS accumulation, and ATF4/CHOP-dependent cell death. Together, these findings demonstrate that diverse models of EGFR inhibitor-resistant NSCLC share the common feature of elevated integrated stress response activity, and that a covalent molecular bridge which activates non-canonical KEAP1-ATF4 signaling can exploit this feature to select against resistance evolution.

2025-12-07 | PXD071547 | Pride

Oscheius sp. MCB isolate:MCB

Project description:Oscheius sp. MCB isolate:MCB Genome sequencing and assembly

| PRJNA275059 | ENA

Steroid receptor coactivation of NRF2 signaling in cardiac fibroblasts promotes resistance to oxidative stress

Project description:We recently discovered that steroid receptor coactivators (SRCs) SRCs-1, 2 and 3, are abundantly expressed in cardiac fibroblasts (CFs) and their activation with the SRC small molecule stimulator MCB-613 improves cardiac function and dramatically lowers pro-fibrotic signaling in CFs post-myocardial infarction (MI). These findings suggest that CF-derived SRC activation could be beneficial in the mitigation of chronic heart failure after ischemic insult. However, the cardioprotective mechanisms by which CFs contribute to cardiac pathological remodeling are unclear. These studies were designed to identify the molecular and cellular circuitry that governs the anti-fibrotic effects of an MCB-613 derivative, MCB-613-10-1, in CFs. To achieve this, we performed cytokine profiling and whole transcriptome analyses of CF-derived signals in response to MCB-613-10-1. We identified the NRF2 pathway as an MCB-613-10-1 therapeutic target for promoting resistance to oxidative stress in CFs. We show that MCB-613-10-1 promotes cell survival of anti-fibrotic CFs exposed to oxidative stress by suppressing apoptosis. We demonstrate that an increase in HMOX1 expression contributes to CF resistance to oxidative stress-mediated apoptosis via a mechanism involving SRC co-activation of NRF2, hence reducing inflammation and fibrosis. We provide evidence that MCB-613-10-1 acts as a protectant against oxidative stress-induced mitochondrial damage. Our data reveal that SRC stimulation of the NRF2 transcriptional network promotes resistance to oxidative stress and highlights a mechanistic approach towards addressing pathologic cardiac remodeling.

2024-10-29 | GSE246877 | GEO

EGFR inhibitor-resistant lung cancers exhibit collateral sensitivity to a covalent, cysteine-independentKEAP1 oligomerizing molecular bridge

2025-02-07 | MSV000097077 | MassIVE

USP15-dependent lysosomal pathway controls p53-R175H turnover in ovarian cancer cells

Project description:Gain-of-function p53 mutants such as p53-R175H form stable aggregates that accumulate in cells and play an important role in cancer progression. Selective degradation of gain-of-function p53 mutants has emerged as a highly attractive therapeutic strategy to target cancer cells harboring specific p53 mutations. We identified a small molecule called MCB-613 to cause rapid ubiquitination, nuclear export, and degradation of p53-R175H through lysosome-mediated pathway leading to catastrophic cancer cell death. In contrast to its effect on the p53-R175H mutant, MCB-613 causes slight stabilization of p53-WT and has weaker effects on other p53 gain-of-function mutants. Using state-of-the-art genetic and chemical approaches, we identified the deubiquitinase USP15 as the mediator of MCB-613’s effect on p53-R175H and established USP15 as a selective upstream regulator of p53-R175H in ovarian cancer cells. These results confirm that distinct pathways regulate the turnover of p53-WT and the different p53 mutants and open new opportunities to selectively target them.

2018-02-07 | GSE110220 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data