Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Anti-tumor efficacy of a potent and selective non-covalent KRASG12D inhibitor

ABSTRACT: We report the expression result for the invivo and invitro cell lines treated with MRTX1133

ORGANISM(S): Homo sapiens

PROVIDER: GSE201412 | GEO | 2022/04/28

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Identification of a potent and selective covalent Pin1 inhibitor.

Project description: Not available

| S-EPMC7442691 | biostudies-literature

Dual inhibition of KRASG12D and pan-ERBB is synergistic in pancreatic ductal adenocarcinoma

Project description:Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with a low survival rate. Recently, new drugs that target KRASG12D, a common mutation in PDAC, have been developed. We studied one of these compounds, MRTX1133, and found it was specific and effective at low nanomolar concentrations in patient-derived organoid models and cell lines harboring KRASG12D mutations. Treatment with MRTX1133 upregulated the expression and phosphorylation of EGFR and HER2, indicating that inhibition of ERBB signaling may potentiate MRTX1133 anti-tumor activity. Indeed, the irreversible pan-ERBB inhibitor, afatinib, potently synergized with MRTX1133 in vitro, and cancer cells with acquired resistance to MRTX1133 in vitro remained sensitive to this combination therapy. Finally, the combination of MRTX1133 and afatinib led to tumor regression and longer survival in orthotopic PDAC mouse models. These results suggest that dual inhibition of ERBB and KRAS signaling may be synergistic and circumvent the rapid development of acquired resistance in patients with KRAS mutant pancreatic cancer.

2023-06-09 | GSE234449 | GEO

Development of potent and selective KDM5 covalent inhibitors

Project description:Histone lysine demethylase (KDMs) are involved in the dynamic regulation of gene expression by reversible regulation of the methylation levels on lysine residues in histone tails. Among the KDMs, the jumonji (JmjC)-domain-containing KDMs (KDM2-7) are Fe(II), 2- OG (α-ketoglutarate) and molecular oxygen-dependent enzymes that employ an oxygenase mechanism to demethylate specific methylation states at various histone sites. KDMs play a critical role in several biological processes such as cell differentiation, inflammation, cancer progression and resistance. Achieving selectivity over the different families of KDMs has been a major challenge. Here we report potent and selective KDM5 covalent inhibitors designed to target a cysteine residue only present in the KDM5 sub-family. In vitro assays show that compounds are selective for the KDM5 sub-family, showing potencies in the low nanomolar range, with higher affinity for KDM5A/B. The covalent binding to the targeted proteins was proved by MS. A kinetic approach was studied in order to describe the components of overall inhibitor potency (reversible binding and chemical reactivity), showing a time-dependent decrease of IC50 values for irreversible inhibition. Additional 2-OG competition assays show that compounds were non 2-OG competitive and target engagement and ChIPs-seq assays showed that the compounds inhibited the KDM5 members in cells in the low micromolar and they induce a global increase of the H3K4Me3 mark.

2018-12-10 | GSE118589 | GEO

Discovery of a potent and selective covalent inhibitor and activity-based probe for UCHL1, with anti-fibrotic activity

Project description:Ubiquitin carboxy-terminal hydrolase L1 (UCHL1) is a deubiquitinating enzyme (DUB) that is very highly expressed in human brain. UCHL1 has been proposed as a potential therapeutic target in neurodegeneration, cancer, and liver and lung fibrosis, however bona fide molecular functions of UCHL1 are yet to be elucidated. Herein we characterize a potent and selective inhibitor and activity-based probe (IMP-1710) for UCHL1 based on a covalent inhibitor scaffold, and its application to identify and quantify target proteins in intact human cells. IMP-1710 stereoselectively labels the catalytic cysteine of UCHL1 at low nanomolar concentration, and we show that a previously claimed UCHL1 inhibitor (LDN-57444) fails to engage UCHL1 in cells. We further demonstrate that potent UCHL1 inhibitors selectively block pro-fibrotic responses in a cellular model of idiopathic pulmonary fibrosis (IPF), supporting a potential therapeutic role for UCHL1 inhibition.

2020-11-12 | PXD015825 | Pride

Mithramycin Depletes Sp1 and Activates p53 to Mediate Senescence and Apoptosis of Pleural Mesothelioma Cells

Project description:We used microarrays to detail the global gene expression of mithramycin treated cells, xenografts and sp1 depleted cells with p53 overexpression. MPM cells and xenografts were treated with mithramycin or SP1 depleted/p53 overexpressed MPM cells were selected for RNA extraction and hybridization on Affymetrix microarrays. We sought to see the invitro and invivo effect of mithramycin (pharmacological model) and depletion of SP1 and overexpression of p53 (genetic model).

2015-01-07 | E-GEOD-64738 | biostudies-arrayexpress

Structure-Guided Development of a Potent and Selective Non-covalent Active-Site Inhibitor of USP7.

Project description: Not available

| S-EPMC5749250 | biostudies-literature

Discovery of potent and selective covalent inhibitors of JNK.

Project description: Not available

| S-EPMC3270411 | biostudies-literature

Development of potent and selective KDM5 covalent inhibitors

Project description:Development of potent and selective KDM5 covalent inhibitors

| PRJNA486160 | ENA

Structure-Based Design of a Potent and Selective Covalent Inhibitor for SRC Kinase That Targets a P-Loop Cysteine.

Project description: Not available

| S-EPMC7493195 | biostudies-literature

Proteomics, metabolomics and single cell proteomics of cells treated with KRASG12D inhibitor MRTX1133

Project description:The metabolomics data from a multiomics study of the cellular response to a KRASG12D inhibitor, MRTX1133. This repository will accompany the completed bulk pasedDIA analysis of cells treated with inhibitor and approximately 3,000 single cells treated with the same dose and conditions.

2023-01-22 | MSV000091110 | MassIVE

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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