Cancer is one of the highest causes of death worldwide. Protein kinase C (PKC) is a family of kinases divided into three groups according to their regulatory domain structure and cofactors requirement for activation: classical, novel, and atypical PKCs. Recently, PKC family isoforms have been the focus of intense research, and recognized as therapeutic targets in anticancer drug development [1]. Diterpenoids are commonly found in the Plectranthus spp., and have a widespread spectrum of biological activity, namely anticancer properties [2]. The diterpenoid 7α-acetoxy-6β-hydroxyroyleanone (AHR) isolated from P. grandidentatus displays low cytotoxicity and the basic requirements approaches for the development of pharmaceutical formulations based on AHR as a lead. These AHR features includes an extraction optimization and structural and thermal properties characterization [3]. These features suggests that AHR can be used as a lead for drug development. Considering this, a small library of abietane derivatives was tested for their ability to activate PKC isoforms from classical (alpha, α; beta, β), novel (delta, d; epsilon, e) and atypical (zeta, z) subfamilies, using a previously developed yeast-based screening assay to search for modulators of PKC isoforms [4]. The results obtained revealed potent activators of PKC family proteins, namely: a selective activator of PKCd, the 7α-acetoxy-6β-benzoyloxy-12-O-benzoylroyleanone (Roy-Bz). The patented diterpenoid RoyBz was prepared using AHR as starting material. Roy-Bz potently inhibited the proliferation of colon cancer cells by inducing a PKCd-dependent mitochondrial apoptotic pathway involving caspase-3 activation. The results indicate that Roy-Bz targets drug resistant cancer stem cells, in HCT116 colon cancer cells, preventing tumor dissemination and recurrence. Moreover, these findings support a tumor suppressive function of PKCd in colon cancer. Overall, these results point to promising activators of PKCs with high potency and isoform-selectivity that may emerge from the exploitation of this new family of abietane diterpenoids [5]. Molecular docking studies are currently ongoing to further identify new selective abietane diterpenoids as new PKC modulators.