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Midostaurin
Ball-and-stick model of the midostaurin molecule
Clinical data
Trade namesRydapt
Other namesPKC412, 4'-N-benzoylstaurosporine
AHFS/Drugs.comMonograph
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Identifiers
  • (9S,10R,11R,13R)-2,3,10,11,12,13-Hexahydro-10-methoxy-9-methyl-11-(methylamino)-9,13-epoxy-1H,9H-diindolo[1,2,3-gh:3',2',1'-lm]pyrrolo[3,4-j][1,7]benzodiamzonine-1-one
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC35H30N4O4
Molar mass570.649 g·mol−1
3D model (JSmol)
  • C[C@@]12[C@@H]([C@@H](C[C@@H](O1)N3C4=CC=CC=C4C5=C6C(=C7C8=CC=CC=C8N2C7=C53)CNC6=O)N(C)C(=O)C9=CC=CC=C9)OC
  • InChI=1S/C35H30N4O4/c1-35-32(42-3)25(37(2)34(41)19-11-5-4-6-12-19)17-26(43-35)38-23-15-9-7-13-20(23)28-29-22(18-36-33(29)40)27-21-14-8-10-16-24(21)39(35)31(27)30(28)38/h4-16,25-26,32H,17-18H2,1-3H3,(H,36,40)/t25-,26-,32-,35+/m1/s1
  • Key:BMGQWWVMWDBQGC-IIFHNQTCSA-N

Midostaurin, sold under the brand name Rydapt by Novartis, is a multi-targeted protein kinase inhibitor that has been investigated for the treatment of acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and advanced systemic mastocytosis. It is a semi-synthetic derivative of staurosporine, an alkaloid from the bacterium Streptomyces staurosporeus.

The US Food and Drug Administration (FDA) considers it to be a first-in-class medication.[4]

AML and MDS

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Midostaurin was found to be active against oncogenic CD135 (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 II clinical trials, midostaurin was found to prolong survival of FLT3-mutated AML patients when combined with conventional induction 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.

Systemic mastocytosis

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Over 95% of patients with adult onset systemic mastocytosis and approximately 40% of children with cutaneous mastocytosis are positive for the D816V c-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 an open-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 variant mast cell leukemia.[8]

Side effects

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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]

References

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  1. ^ "MIDOSTAURIN (Dr Reddys Laboratories Australia Pty Ltd) | Therapeutic Goods Administration (TGA)". Archived from the original on 16 April 2025. Retrieved 5 October 2025.
  2. ^ "Cancer therapies". Health Canada. 8 May 2018. Retrieved 13 April 2024.
  3. ^ "Rydapt EPAR". European Medicines Agency. 18 September 2017. Retrieved 29 June 2024.
  4. ^ New Drug Therapy Approvals 2017. U.S. Food and Drug Administration (FDA) (Report). January 2018. Archived from the original (PDF) on 14 September 2019. Retrieved 16 September 2020.
  5. ^ Weisberg E, Boulton C, Kelly LM, Manley P, Fabbro D, Meyer T, et al. (June 2002). "Inhibition of mutant FLT3 receptors in leukemia cells by the small molecule tyrosine kinase inhibitor PKC412". Cancer Cell. 1 (5): 433–43. doi:10.1016/S1535-6108(02)00069-7. PMID 12124173.{{cite journal}}: CS1 maint: overridden setting (link)
  6. ^ Stone RM, Mandrekar S, Sanford BL, Geyer S, Bloomfield CD, Dohner K, et al. (December 2015). The multi-kinase inhibitor midostaurin (M) prolongs survival compared with placebo (P) in combination with daunorubicin (D)/cytarabine (C) induction (ind), high-dose C consolidation (consol), and as maintenance (maint) therapy in newly diagnosed acute myeloid leukemia (AML) patients (pts) age 18–60 with FLT3 mutations (muts): An international prospective randomized (rand) P-controlled double-blind trial (CALGB 10603/RATIFY [Alliance]). American Society of Hematology (ASH) 57th Annual Meeting. Orlando.{{cite conference}}: CS1 maint: overridden setting (link)
  7. ^ Office of the Commissioner. "Press Announcements - FDA approves new combination treatment for acute myeloid leukemia". www.fda.gov. Archived from the original on 28 April 2017. Retrieved 4 May 2017.
  8. ^ Gotlib J, Kluin-Nelemans HC, George TI, Akin C, Sotlar K, Hermine O, et al. (June 2016). "Efficacy and Safety of Midostaurin in Advanced Systemic Mastocytosis". The New England Journal of Medicine. 374 (26): 2530–41. doi:10.1056/nejmoa1513098. PMID 27355533.{{cite journal}}: CS1 maint: overridden setting (link)
  9. ^ Drugs.com: rydapt overview.

📚 Artikel Terkait di Wikipedia

Staurosporine

is the precursor of the novel protein kinase inhibitor midostaurin (PKC412). Besides midostaurin, staurosporine is also used as a starting material in

Mastocytosis

include immunodeficiency and infections. Tyrosine kinase inhibitors (TKI) Midostaurin. TKI acting on many different tyrosine kinases, approved by FDA and EMA

Mast cell

target MCs include the following: Omalizumab (targets IgE); Imatinib, Midostaurin and Avapritinib (target KIT); and Cetirizine, Levocetirizine, Bilastine

Acute myeloid leukemia

Transplantation. The targeted therapies currently approved by the FDA are: Midostaurin Gilteritinib Quizartinib Ivosidenib Olutasidenib Enasidenib Venetoclax

First-in-class medication

dendritic cells Blastic plasmacytoid dendritic cell neoplasm 2018 2021 Midostaurin (Rydapt) Multi-target tyrosine kinase inhibitor not inhibited by the

Streptomyces isolates

(Mutamycin), rebeccamycin, staurosporine (precursor to stauprimide and midostaurin), neothramycin, aclarubicin, tomaymycin, sibiromycin, and mazethramycin

ATC code L01

Masitinib L01EX07 Cabozantinib L01EX08 Lenvatinib L01EX09 Nintedanib L01EX10 Midostaurin L01EX11 Quizartinib L01EX12 Larotrectinib L01EX13 Gilteritinib L01EX14

Cucurbitacin

(OSM) Thymic stromal lymphopoietin (TSLP) Additional cytokine receptor modulators: Emfilermin Lestaurtinib Midostaurin Quizartinib Sorafenib Sunitinib