K252a is a staurosporine analog isolated from Nocardiopsis sp. soil fungi that inhibits protein kinase (PK) C, PKA, Ca2+/calmodulin-dependent kinase type II, and phosphorylase kinase with IC50 values of 470, 140, 270, and 1.7 nM, respectively.[1],[2] Because it inhibits neurotrophin receptor tyrosine kinases, K252a at 100-500 nM has been used to suppress trophoblast proliferation and increase apoptosis associated with the disruption of mitochondrial functions in cultured choriocarcinoma cells.[3] Recently, K252a has been shown to inhibit PRK1 (IC50 = 3.2 nM in vitro), a PKC-related kinase that phosphorylates histone H3 at threonine 11 and is involved in androgen-dependent gene expression.[4]
Reference:
[1]. Yasuzawa, T., Iida, T., Yoshida, M., et al. The structures of the novel protein kinase C inhibitors K-252a, b, c AND d. Journal of Antibiotics 39(8), 1072-1078 (1986).
[2]. Davis, P.D., Hill, C.H., Lawton, G., et al. Inhibitors of protein kinase C. 1.1 2,3-bisarylmaleimides. Journal of Medicinal Chemistry 35, 177-184 (1992).
[3]. Kawamura, N., Kawamura, K., Manabe, M., et al. Inhibition of brain-derived neurotrophic factor/tyrosine kinase B signaling suppresses choriocarcinoma cell growth. Endocrinology 151(7), 3006-3014 (2010).
[4]. Köhler, J., Erlenkamp, G., Eberlin, A., et al. Lestaurtinib inhibits histone phosphorylation and androgen-dependent gene expression in prostate cancer cells. PLoS One 7(4), (2012).