Dataset Information

Cooperative induction of apoptosis in nras mutant melanoma by inhibition of mek and rock

ABSTRACT: Data from ProteomeXchange, PXD ID: PXD000528. Experiment: GM_NKI_NRAS_Phospho_Mix2, file: OR9_20130426_GM_NKI_NRAS_Phospho_Mix2_repl1_ReRunFr10.mzml. Published as part of Pigment Cell Melanoma Res. 2015 Feb 28 . From the Abstract: {{i}} No effective targeted therapy is currently available for NRAS mutant melanoma. Experimental MEK inhibition is rather toxic and has only limited efficacy in clinical trials. At least in part, this is caused by the emergence of drug resistance, which is commonly seen for single agent treatment and shortens clinical responses. Therefore, there is a dire need to identify effective companion drug targets for NRAS mutant melanoma. Here, we show that at concentrations where single drugs had little effect, ROCK inhibitors GSK269962A or Fasudil, in combination with either MEK inhibitor GSK1120212 (Trametinib) or ERK inhibitor SCH772984 cooperatively caused proliferation inhibition and cell death in vitro ... {{/i}}

INSTRUMENT(S): Instrument

ORGANISM(S): Homo_sapiens_viruses, Human

DISEASE(S): Not Available

SUBMITTER: Vogel CJ, et al.

PROVIDER: GPM32320014056 | GPMDB |

REPOSITORIES: GPMDB

ACCESS DATA

Publications

Cooperative induction of apoptosis in NRAS mutant melanoma by inhibition of MEK and ROCK.

Vogel Celia J CJ Smit Marjon A MA Maddalo Gianluca G Possik Patricia A PA Sparidans Rolf W RW van der Burg Sjoerd H SH Verdegaal Els M EM Heck Albert J R AJ Samatar Ahmed A AA Beijnen Jos H JH Altelaar A F Maarten AF Peeper Daniel S DS

Pigment cell & melanoma research 20150406 3

No effective targeted therapy is currently available for NRAS mutant melanoma. Experimental MEK inhibition is rather toxic and has only limited efficacy in clinical trials. At least in part, this is caused by the emergence of drug resistance, which is commonly seen for single agent treatment and shortens clinical responses. Therefore, there is a dire need to identify effective companion drug targets for NRAS mutant melanoma. Here, we show that at concentrations where single drugs had little effe ...[more]

PMID: 25728708

Similar Datasets

Project description:Walsh2014 - Inhibition kinetics of DAPT on APP Cleavage This model is described in the article: Are improper kinetic models hampering drug development? Walsh R. PeerJ 2014; 2: e649 Abstract: Reproducibility of biological data is a significant problem in research today. One potential contributor to this, which has received little attention, is the over complication of enzyme kinetic inhibition models. The over complication of inhibitory models stems from the common use of the inhibitory term (1 + [I]/Ki ), an equilibrium binding term that does not distinguish between inhibitor binding and inhibitory effect. Since its initial appearance in the literature, around a century ago, the perceived mechanistic methods used in its production have spurred countless inhibitory equations. These equations are overly complex and are seldom compared to each other, which has destroyed their usefulness resulting in the proliferation and regulatory acceptance of simpler models such as IC50s for drug characterization. However, empirical analysis of inhibitory data recognizing the clear distinctions between inhibitor binding and inhibitory effect can produce simple logical inhibition models. In contrast to the common divergent practice of generating new inhibitory models for every inhibitory situation that presents itself. The empirical approach to inhibition modeling presented here is broadly applicable allowing easy comparison and rational analysis of drug interactions. To demonstrate this, a simple kinetic model of DAPT, a compound that both activates and inhibits ?-secretase is examined using excel. The empirical kinetic method described here provides an improved way of probing disease mechanisms, expanding the investigation of possible therapeutic interventions. This model is hosted on BioModels Database and identified by: BIOMD0000000617. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Dataset Information

Cooperative induction of apoptosis in nras mutant melanoma by inhibition of mek and rock

Publications

Cooperative induction of apoptosis in NRAS mutant melanoma by inhibition of MEK and ROCK.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets