12-Deoxyphorbol-13-isobutyrate-20-acetate

12-Deoxyphorbol-13-isobutyrate-20-acetate is a diterpene ester known to act as an activator of protein kinase C (PKC). It facilitates the phosphorylation of troponin I and troponin T by activating PKC. This compound can induce skin irritation and necrosis in mice but lacks tumor-promoting activity. Furthermore, it exhibits inhibitory effects on the growth of Aspergillus carbonarius. It finds application in research related to heart failure, cardiomyopathy, and fungal infections.

12-Deoxyphorbol-13-isobutyrate-20-acetate (1 μM) reduces the contractility of intact human myocardial trabeculae via a calcium-independent mechanism, with caffeine partially reversing its negative inotropic effect and decrease in myofilament calcium sensitivity. In demembraned human ventricular trabeculae, it reduces myofilament calcium sensitivity by shifting [Ca 2+] 50% to 2.09 μM and decreases maximum force. Additionally, it lowers contractility in intact control and cardiomyopathic ventricular trabeculae and alters the Hill coefficient despite a continuous increase in [Ca 2+] 50%. At concentrations of 10-100 μM over three days, this compound decreases the growth of Aspergillus carbonarius by 25%. Furthermore, 12-Deoxyphorbol-13-isobutyrate-20-acetate (0.001-100 μM; 72 hours) equally reduces the viability of both MCF7 breast cancer cells and MCF10A normal breast cells, showing no selective cytotoxicity towards cancer cells.

12-Deoxyphorbol-13-isobutyrate-20-acetate, administered topically at a dose of 0.024 nmoles per ear, demonstrates an ID50 of 0.024 nmoles per ear for inducing redness in a murine ear irritation model. When applied topically at 0.2 μmoles per dose, twice weekly for 24 weeks, this compound exhibits no detectable co-carcinogenic tumor-promoting activity in NMRI mice initiated with 7,12-dimethylbenz[a]anthracene, with a tumor incidence rate of 0%, a tumor yield of 0, and a mortality rate of 28% over the 24-week period.