ROY-BZ: A SMALL MOLECULE SELECTIVE ACTIVATOR OF PROTEIN KINASE CDELTA (PKCDELTA)

摘要

The present application discloses the use of a family of abietane derivatives as activators of PKC family isoforms. The present application provides a small molecule selective activator of isoform delta of protein kinase C (PKCdelta), the 7alpha-acetoxy- 6beta-benzoyloxy-12-0-benzoylroyleanone (Roy-Bz), a semi-synthetic derivative of the natural diterpenoid 7alpha-acetoxy- 6beta-hydroxyroyleanone (Roy) isolated from a Lamiaceae family plant. Roy-Bz belongs to a novel family of small molecule modulators of PKC activity, the abietane derivatives with the general formula shown in Figure 1 wherein X, Y, Z, W; Rl, R2, R3, R4 and R5 are as defined herein, as a stereoisomer, enantiomer, racemate, tautomer thereof or mixtures thereof; or a pharmaceutically acceptable salt, solvate or prodrug thereof and their use as activators of PKC family isoforms.