The Direct Target of CAPE: AKR1B10 ("Aldo-Keto-Reductase" ) that is essential for RAS/RAC/PAK1 signaling

CAPE (caffeic acid phenethyl ester), the major anti-cancer ingredient in propolis such as Bio 30, has been known to down-regulate RAC that is essential for the activation of the major oncogenic/ageing kinase PAK1. However, the direct target of CAPE remained unknown till recently. 

A few years ago, a group at Gifu College of Pharmacy in Japan identified AKR1B10 ("Aldo-Keto-Reductase" ) as the direct target of CAPE with the IC50=80 nM, and developed a more potent CAPE derivative (called "10C") with the IC50=6 nM (1).  AKR1B10 is essential for the activation of RAS and RAC, which eventually activate PAK1 in cells.  Thus, we wonder if "Nepofein" is more potent than the compound 10C or not in cell culture and in vivo. The cell-permeability of "compound 10C" is still very low, and the IC50 against cancer cell growth (or AKR1B10 ) in cell culture is around 300 nM, indicating that only 1/50 of this compound enters cells.

References:

1. Soda M, Hu D, Endo S, Takemura M, Li J, Wada R, Ifuku S, Zhao HT, El-Kabbani O, Ohta S, Yamamura K, Toyooka N, Hara A, Matsunaga T.

Design, synthesis and evaluation of caffeic acid phenethyl ester (CAPE) -based inhibitors targeting a selectivity pocket in the active site of human aldo-keto reductase 1B10. Eur J Med Chem. 2012 ; 48:321-9.