Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Identifying and overcoming a mechanism of resistance to Wee1 kinase inhibitor AZD1775 in high grade serous ovarian cancer cells (OVCAR8)

ABSTRACT: Treatment of Human high grade serous ovarian cancer cell line, OVCAR8, with WEE1 kinase inhibitor AZD1775

ORGANISM(S): Homo sapiens

PROVIDER: GSE141990 | GEO | 2020/12/01

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Identifying and overcoming a mechanism of resistance to Wee1 kinase inhibitor AZD1775 in high grade serous ovarian cancer cells (ES-2)

Project description:Treatment of Human high grade serous ovarian cancer cell line, ES-2, with WEE1 kinase inhibitor AZD1775

2020-12-01 | GSE142124 | GEO

Identifying and overcoming a mechanism of resistance to Wee1 kinase inhibitor AZD1775 in high grade serous ovarian cancer cells (OVCAR8)

Project description:Identifying and overcoming a mechanism of resistance to Wee1 kinase inhibitor AZD1775 in high grade serous ovarian cancer cells (OVCAR8)

| PRJNA595516 | ENA

Identifying and overcoming a mechanism of resistance to Wee1 kinase inhibitor AZD1775 in high grade serous ovarian cancer cells

Project description:Identifying and overcoming a mechanism of resistance to Wee1 kinase inhibitor AZD1775 in high grade serous ovarian cancer cells

| PRJNA595941 | ENA

Identifying and overcoming a mechanism of resistance to Wee1 kinase inhibitor AZD1775 in high grade serous ovarian cancer cells (ES-2)

Project description:Identifying and overcoming a mechanism of resistance to Wee1 kinase inhibitor AZD1775 in high grade serous ovarian cancer cells (ES-2)

| PRJNA595945 | ENA

Dual role of the unfolded protein response in the therapeutic effect of AZD1775 on TP53 mutant high grade serous ovarian cancer

Project description:we demonstrate that the WEE1 inhibitor AZD1775 triggers endoplasmic reticulum (ER) stress and activates the PERK and IRE1α branches of the unfolded protein response (UPR) in TP53 mutant HGSOC cells. Upon AZD1775 treatment, PERK facilitates apoptotic signaling in these cells via activating CHOP, whereas IRE1α-induced spliced XBP1 (XBP1s) confers survival in response to WEE1 inhibition. Our data uncover an important dual role of UPR in TP53 mutant HGSOC cells in response to AZD1775, where additional inhibition of IRE1α-XBP1s signaling may offer synergistic efficacy.

2021-02-10 | GSE166417 | GEO

Mechanistic study of Wee1 kinase inhibition with AZD1775 exposes drug targetable vulnerabilities in acute B-lymphoblastic leukemia [scATAC-seq]

Project description:This study characterized the effect of WEE1 kinase inhibition using AZD1775 treatment on single-cell accessible chromatin and gene expression profile in the acute lymphoblastic leukemia cell line RS4;11 that represents the KMT2A-rearranged subtype.

2023-05-14 | GSE218805 | GEO

Mechanistic study of Wee1 kinase inhibition with AZD1775 exposes drug targetable vulnerabilities in acute B-lymphoblastic leukemia [scRNA-seq PDX MLL-7]

Project description:This study characterized the effect of WEE1 kinase inhibition using AZD1775 treatment on single-cell gene expression profile using the 10x Genomics protocol in the acute lymphoblastic leukemia cells

2023-05-14 | GSE220476 | GEO

Mechanistic study of Wee1 kinase inhibition with AZD1775 exposes drug targetable vulnerabilities in acute B-lymphoblastic leukemia [scRNA-seq]

2023-05-14 | GSE218621 | GEO

Mechanistic study of Wee1 kinase inhibition with AZD1775 exposes drug targetable vulnerabilities in acute B-lymphoblastic leukemia [scMultiome]

Project description:This study characterized the effect of WEE1 kinase inhibition using AZD1775 treatment on single-cell accessible chromatin and gene expression profile using the 10x Genomics multiome protocol (ATAC + Gene Expression Assay) in the acute lymphoblastic leukemia cell line RS4;11 that represents the KMT2A-rearranged subtype.

2023-05-14 | GSE220112 | GEO

Development and Characterization of a Wee1 Kinase Degrader

Project description:The G1/S cell-cycle checkpoint is frequently dysregulated in cancer, leaving cancer cells particularly reliant on a functional G2/M checkpoint to prevent excessive DNA damage. Inhibiting regulators of the G2/M checkpoint can therefore drive cancer cells into premature mitosis, ultimately causing cell death by mitotic catastrophe. One such regulator is Wee1, a nuclear tyrosine kinase that delays mitotic entry by phosphorylating CDK1 at Tyr15. Previous drug development efforts targeting Wee1 resulted in the clinical-grade inhibitor, AZD1775. However, AZD1775 is burdened by dose- limiting adverse events, and has off-target PLK1 activity. In an attempt to overcome these limitations, we designed small molecule degraders of Wee1 by conjugating AZD1775 to the cereblon (CRBN)- binding ligand, pomalidomide, as informed by molecular docking. The resulting lead compound, ZNL- 02-096, degrades Wee1 while sparing PLK1, induces G2/M phase accumulation at up to 10-fold lower concentrations than AZD1775, and potently synergizes with Olaparib in ovarian cancer cell lines. We demonstrate that ZNL-02-096 has CRBN-dependent pharmacology that is distinct from the conventional catalytic inhibitor, AZD1775, which justifies further evaluation of selective Wee1 degraders.

2019-11-18 | PXD015513 | Pride

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