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| Trade names | Rydapt |
| Other names | PKC412, 4'-N-benzoylstaurosporine |
| AHFS/Drugs.com | Monograph |
| Routes of administration | By mouth |
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| Chemical and physical data | |
| Formula | C35H30N4O4 |
| Molar mass | 570.649 g·mol−1 |
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Midostaurin, sold under the brand nameRydapt byNovartis, is a multi-targetedprotein kinase inhibitor that has been investigated for the treatment ofacute myeloid leukemia (AML),myelodysplastic syndrome (MDS) and advancedsystemic mastocytosis. It is a semi-synthetic derivative ofstaurosporine, analkaloid from the bacteriumStreptomyces staurosporeus.
The USFood and Drug Administration (FDA) considers it to be afirst-in-class medication.[4]
Midostaurin was found to be active against oncogenicCD135 (FMS-like tyrosine kinase 3 receptor, FLT3), in preclinical studies.[5] Clinical trials have primarily focused on relapsed/refractory AML and MDS and have included single agent and combination agent studies. After successful Phase IIclinical trials, midostaurin was found to prolong survival of FLT3-mutated AML patients when combined with conventionalinduction and consolidation therapies in a randomized Phase III clinical trial.[6] On 28 April 2017, midostaurin was approved by the FDA for the treatment of adult patients with newly diagnosed AML who are positive for oncogenic FLT3, in combination with chemotherapy.[7] The drug is approved for use with a companion diagnostic, the LeukoStrat CDx FLT3 Mutation Assay, which is used to detect the FLT3 mutation in patients with AML.
Over 95% of patients with adult onset systemicmastocytosis and approximately 40% of children withcutaneous mastocytosis are positive for the D816Vc-Kit activating mutation, which renders c-Kit resistant to currently available tyrosine kinase inhibitors. Midostaurin is an investigational treatment in patients with advanced forms of systemic mastocytosis and D816V c-Kit mutation with a subset of patients achieving clinical response. In anopen-label study of patients with mastocytosis-related organ damage (89 eligible patients meeting inclusion for the primary efficacy population), midostaurin showed efficacy in patients with advanced systemic mastocytosis, including the highly fatal variantmast cell leukemia.[8]
Common side effects include immune system related problems (fever,febrile neutropenia),blood clotting problems (bruising, nosebleed), and unspecific symptoms such as diarrhea,nausea and headache.Upper respiratory tract infections can be dangerous.[9]
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