Class/mechanism: FLT3 inhibitor, tyrosine kinase inhibitor (TKI). Midostaurin or its active metabolites CGP62221 and CGP52421 inhibit activity of wild type FLT3, FLT3 mutant kinases (ITD and TKD), KIT (wild type and D816V mutant), PDGFRα/β, VEGFR2, and members of the serine/threonine kinase PKC (protein kinase C) family. Midostaurin induced apoptosis in leukemic cells expressing ITD and TKD mutant FLT3 receptors or overexpressing wild type FLT3 and PDGF receptors. Midostaurin also causes apoptosis in mast cells and inhibits histamine release, proliferation, and KIT signaling.
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Diseases for which it is used
Patient drug information
History of changes in FDA indication
- 4/28/2017: FDA approved for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) who are FLT3 mutation-positive (FLT3+), as detected by an FDA-approved test, in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation.
- 4/28/2017: FDA approved for the treatment of adults with aggressive systemic mastocytosis (SM), SM with associated hematological neoplasm, or mast cell leukemia.
- Heidel F, Solem FK, Breitenbuecher F, Lipka DB, Kasper S, Thiede MH, Brandts C, Serve H, Roesel J, Giles F, Feldman E, Ehninger G, Schiller GJ, Nimer S, Stone RM, Wang Y, Kindler T, Cohen PS, Huber C, Fischer T. Clinical resistance to the kinase inhibitor PKC412 in acute myeloid leukemia by mutation of Asn-676 in the FLT3 tyrosine kinase domain. Blood. 2006 Jan 1;107(1):293-300. Epub 2005 Sep 8. link to original article PubMed
Also known as
- Code name: PKC412
- Brand name: Rydapt