Chemical Proteomics Identifies SLC25A20 as a Functional Target of the Ingenol Class of Actinic Keratosis Drugs.

ABSTRACT: The diterpenoid ester ingenol mebutate (IngMeb) is the active ingredient in the topical drug Picato, a first-in-class treatment for the precancerous skin condition actinic keratosis. IngMeb is proposed to exert its therapeutic effects through a dual mode of action involving (i) induction of cell death that is associated with mitochondrial dysfunction followed by (ii) stimulation of a local inflammatory response, at least partially driven by protein kinase C (PKC) activation. Although this therapeutic model has been well characterized, the complete set of molecular targets responsible for mediating IngMeb activity remains ill-defined. Here, we have synthesized a photoreactive, clickable analogue of IngMeb and used this probe in quantitative proteomic experiments to map several protein targe

SUBMITTER: Parker CG 

PROVIDER: S-EPMC5746860 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature