Description
PKC412 is an anti-metastatic and anticancer chemotherapeutic staurosporine derivative that inhibits FMS-like tyrosine kinase 3 (FLT3) and is currently in clinical trials as a potential treatment for acute myelogenous leukemia (AML). PKC412 also inhibits PKC. In keloid-derived fibroblasts, PKC412 increases activity of caspase 3, inducing apoptosis. In animal models of melanoma, PKC412 inhibits metastasis and platelet-aggregating activity. This compound also alters differentiation patterns of dendritic cells ex vivo.
References
Fischer T, Stone RM, Deangelo DJ, et al. Phase IIB trial of oral Midostaurin (PKC412), the FMS-like tyrosine kinase 3 receptor (FLT3) and multi-targeted kinase inhibitor, in patients with acute myeloid leukemia and high-risk myelodysplastic syndrome with either wild-type or mutated FLT3. J Clin Oncol. 2010 Oct 1;28(28):4339-45. PMID: 20733134.
Huang YC, Shieh HR, Chen YJ. Midostaurin (PKC412) modulates differentiation and maturation of human myeloid dendritic cells. Toxicol In Vitro. 2010 Sep;24(6):1705-10. PMID: 20685248.
Stölzel F, Steudel C, Oelschlägel U, et al. Mechanisms of resistance against PKC412 in resistant FLT3-ITD positive human acute myeloid leukemia cells. Ann Hematol. 2010 Jul;89(7):653-62. PMID: 20119833.
Nakazono-Kusaba A, Takahashi-Yanaga F, Miwa Y, et al. PKC412 induces apoptosis through a caspase-dependent mechanism in human keloid-derived fibroblasts. Eur J Pharmacol. 2004 Aug 23;497(2):155-60. PMID: 15306200.
Yoshikawa N, Nakamura K, Yamaguchi Y, et al. Effect of PKC412, a selective inhibitor of protein kinase C, on lung metastasis in mice injected with B16 melanoma cells. Life Sci. 2003 Feb 7;72(12):1377-87. PMID: 12527035.
