Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

LINCS Pilot Phase Joint Project: Sensitivity measures of six breast cancer cell lines to a library of small molecule kinase inhibitors (drug combination treatments). Dataset 1 of 2: Cell count and normalized growth rate inhibition values.

ABSTRACT: -

SUBMITTER: Marc Hafner, Mario Niepel

PROVIDER: LDS-1294 | LINCS | 2016-04-01

REPOSITORIES: LINCS

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	HMS_LINCS&file=LDS-1294.tar.gz	Other

Items per page:

1 - 1 of 1

Similar Datasets

LINCS Pilot Phase Joint Project: Sensitivity measures of six breast cancer cell lines to a library of small molecule kinase inhibitors (drug combination treatments). Dataset 2 of 2: Mean cell count and mean normalized growth rate inhibition values across technical replicates.

Project description:-

2016-04-01 | LDS-1295 | LINCS

LiP-Quant, an automated chemoproteomic approach to identify drug targets in complex proteomes, p3

Project description:LiP-Quant MS sample preparation for target deconvolution

2020-09-09 | PXD019902 | Pride

LINCS Pilot Phase Joint Project: Sensitivity measures of six breast cancer cell lines to a library of small molecule kinase inhibitors (single drug treatments). Dataset 15 of 15: Calculated dose-response metrics.

Project description:-

2017-03-14 | LDS-1257 | LINCS

Infection-induced resistance to experimental cerebral malaria

Project description:Cerebral malaria (CM) is one of the most severe complications of malaria infection. There is evidence that repeated parasite exposure promotes resistance against CM, as indicated by the low incidence of CM in adults in malaria-endemic regions. However, the immunological basis of this infection-induced resistance remains poorly understood. Here, a microarray study done utilising the tractable Plasmodium berghei ANKA model of experimental cerebral malaria (ECM), we show that three rounds of infection and drug-cure protects against the development of ECM during a subsequent fourth infection.

2019-02-19 | E-MTAB-5513 | biostudies-arrayexpress

Topoisomerase II inhibitors and histone eviction

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-06-04 | E-GEOD-33634 | biostudies-arrayexpress

Differential network analysis of ROS1 inhibitors reveals lorlatinib polypharmacology: Chemical Proteomics

Project description:Multiple tyrosine kinase inhibitors (TKIs) are often developed for the same indication. However, their relative overall efficacy is frequently incompletely understood and they may harbor unrecognized targets that cooperate with the intended target. We compared several ROS1 TKIs for inhibition of ROS1-fusion-positive lung cancer cell viability, ROS1 autophosphorylation and kinase activity, which indicated disproportionately higher cellular potency of one TKI, lorlatinib. Quantitative chemical and phosphoproteomics across four ROS1 TKIs and differential network analysis revealed that lorlatinib uniquely impacted focal adhesion signaling. Functional validation using kinase assays, pharmacological probes and RNA interference uncovered a polypharmacology mechanism of lorlatinib by dual targeting ROS1 and PYK2, which form a multiprotein complex with SRC. Rational multi-targeting of this complex by combining lorlatinib with SRC inhibitors exhibited pronounced synergy. Taken together, we show that systems pharmacology-based differential network analysis can dissect mixed canonical/non-canonical polypharmacology mechanisms across multiple TKIs enabling the design of rational drug combinations.

2024-04-05 | PXD031690 | Pride

Project Name: Functional proteomics of midostaurin in lung cancer cells: Chemical Proteomics

Project description:Lung cancer is associated with high prevalence and mortality, and despite significant successes with targeted drugs in genomically defined subsets of lung cancer and immunotherapy, the majority of patients currently does not benefit from these therapies. Through a targeted drug screen, we found the recently approved multi-kinase inhibitor midostaurin to have potent activity in several lung cancer cells independent of its intended target, PKC, or a specific genomic marker. To determine the underlying mechanism of action we applied a layered functional proteomics approach and a new data integration method. Using chemical proteomics, we identified multiple midostaurin kinase targets in these cells. Network-based integration of these targets with quantitative tyrosine and global phosphoproteomics data using protein-protein interactions from the STRING database suggested multiple targets are relevant for the mode of action of midostaurin. Subsequent functional validation using RNA interference and selective small molecule probes showed that simultaneous inhibition of TBK1, PDK1 and AURKA was required to elicit midostaurin’s cellular effects. Immunoblot analysis of downstream signaling nodes showed that combined inhibition of these targets altered PI3K/AKT and cell cycle signaling pathways that in part converged on PLK1. Furthermore, rational combination of midostaurin with the more potent PLK1 inhibitor BI2536, which is in advanced clinical trials, elicited strong synergy. Our results demonstrate that combination of complementary functional proteomics approaches and subsequent network-based data integration can reveal novel insight into the complex mode of action of multi-kinase inhibitors, actionable targets for drug discovery and cancer vulnerabilities. Finally, we illustrate how this knowledge can be utilized for the rational design of synergistic drug combinations with high potential for clinical translation.

2018-09-24 | PXD010787 | Pride

LINCS Pilot Phase Joint Project: Sensitivity measures of six breast cancer cell lines to a library of small molecule kinase inhibitors (single drug treatments). Dataset 11 of 15: Mean cell count and mean normalized growth rate inhibition values across biological replicate 1.

Project description:-

2017-03-14 | LDS-1253 | LINCS

LINCS Pilot Phase Joint Project: Sensitivity measures of six breast cancer cell lines to a library of small molecule kinase inhibitors (single drug treatments). Dataset 10 of 15: Cell count and normalized growth rate inhibition values within biological replicate 3.

Project description:-

2017-03-14 | LDS-1252 | LINCS

LINCS Pilot Phase Joint Project: Sensitivity measures of six breast cancer cell lines to a library of small molecule kinase inhibitors (single drug treatments). Dataset 3 of 15: Cell count and relative growth within biological replicate 3.

Project description:-

2017-03-14 | LDS-1228 | LINCS