Proteomics

Dataset Information

0

Dual protein kinase/ nucleoside kinase modulat ors for rationally designed polypharmacology


ABSTRACT: Masitinib, a highly selective protein kinase inhibitor, can sensitise gemcitabine-refractory cancer cell lines when used in combination with gemcitabine. A reverse proteomic approach has identified the target responsible for this sensitisation: the deoxycytidine kinase (dCK). Masitinib, as well as other protein kinase inhibitors such as imatinib, interact with dCK and provoke an unforeseen conformational-dependent activation of this nucleoside kinase, modulating phosphorylation of nucleoside analogue drugs. This phenomenon leads to an increase of prodrug phosphorylation of most of the chemotherapeutic drugs activated by this nucleoside kinase. The unforeseen dual activity of protein kinase inhibition/nucleoside kinase activation could be of great therapeutic benefit, through either reducing toxicity of therapeutic agents by maintaining effectiveness at lower doses or by counteracting drug resistance initiated via down modulation of dCK target.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Permanent Cell Line Cell, Cell Culture

DISEASE(S): Colon Cancer

SUBMITTER: AUDEBERT Stephane  

LAB HEAD: Audebert Stephane

PROVIDER: PXD007765 | Pride | 2017-11-13

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
HMC1_Beads.raw Raw
HMC1_Beads_140328223216.raw Raw
HMC1_Beads_140329010544.raw Raw
HMC1_Masitinib.raw Raw
HMC1_Masitinib_140329080705.raw Raw
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Publications


Masitinib, a highly selective protein kinase inhibitor, can sensitise gemcitabine-refractory cancer cell lines when used in combination with gemcitabine. Here we report a reverse proteomic approach that identifies the target responsible for this sensitisation: the deoxycytidine kinase (dCK). Masitinib, as well as other protein kinase inhibitors, such as imatinib, interact with dCK and provoke an unforeseen conformational-dependent activation of this nucleoside kinase, modulating phosphorylation  ...[more]

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