Background:

Chelerythrine is a potent, selective antagonist of PKC (protein kinase C) with IC50 value of 0.66 μM.[1]

The alkaloid chelerythrine is a highly specific inhibitor that acts at the regulatory domain of the kinase.[2] It is also a competitive inhibitor with respect to the phosphate acceptor and a non-competitive inhibitor with respect to ATP.[1] Chelerythrine induced a dose-dependent decrease in the cell viability with IC50 value of 2.6 μM measured by MTT reduction assay.[3] Chelerythrine is also a selective and strong inhibitor of Bcl-xL functions and induced cell death in MEF cells with IC50 value of 1.1 μM.[4] Chelerythrine activated MEKK1- and MKK4-dependent JNK1 and p38 pathways then mediated the induction of apoptosis.[5] Chelerythrine stimulated apoptosis in the in vivo rat experiments (5 mg/kg) by inducing the generation of reactive oxygen species.[6] Chelerythrine also has widespread physiological effects on primarily antimicrobial and anti-inflammatory.

参考文献:
1. J. M. Herbert, J. M. Augereau, J. Gleye and J. P. Maffrand, Biochem Biophys Res Commun 1990, 172, 993-999.
2. W. D. Jarvis, A. J. Turner, L. F. Povirk, R. S. Traylor and S. Grant, Cancer Res 1994, 54, 1707-1714.
3. J. Vrba, P. Dolezel, J. Vicar, M. Modriansky and J. Ulrichova, Toxicol In Vitro 2008, 22, 1008-1017.
4. M. Vogler, K. Weber, D. Dinsdale, I. Schmitz, K. Schulze-Osthoff, M. J. Dyer and G. M. Cohen, Cell Death Differ 2009, 16, 1030-1039.
5. R. Yu, S. Mandlekar, T. H. Tan and A. N. Kong, J Biol Chem 2000, 275, 9612-9619.
6. S. Yamamoto, K. Seta, C. Morisco, S. F. Vatner and J. Sadoshima, J Mol Cell Cardiol 2001, 33, 1829-1848.