midostaurin   Click here for help

GtoPdb Ligand ID: 5702

Synonyms: CGP 41231 | CGP 41251 | N-benzoylstaurosporine | PKC412 | Rydapt®
Approved drug PDB Ligand Immunopharmacology Ligand
midostaurin is an approved drug (FDA & EMA (2017))
Compound class: Synthetic organic
Comment: Midostaurin is an analogue of staurosporine, and was originally described as a PKC inhibitor [5]. It was later reported as an inhibitor of fms-related tyrosine kinase 3 (FLT3) [6].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 1
Rotatable bonds 4
Topological polar surface area 77.73
Molecular weight 570.23
XLogP 7.8
No. Lipinski's rules broken 1
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Canonical SMILES COC1C(CC2OC1(C)n1c3ccccc3c3c1c1n2c2ccccc2c1c1c3CNC1=O)N(C(=O)c1ccccc1)C
Isomeric SMILES CO[C@@H]1[C@@H](C[C@H]2O[C@]1(C)n1c3ccccc3c3c1c1n2c2ccccc2c1c1c3CNC1=O)N(C(=O)c1ccccc1)C
InChI 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
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Summary of Clinical Use Click here for help
The FDA granted midostaurin accelerated approval in April 2017, and the EMA followed in September of the same year. These authorisations are for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) who are FLT3 mutation-positive (as detected by an FDA-approved test) to be used in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation. It was also approved for mastocytosis [3]. The EMA had previously granted midostaurin orphan drug designation for the treatment of AML and mastocytosis (effective via inhibition of KIT receptors on mast cells, which are involved in stimulating proliferation of mast cells in mastocytosis).
Click here to link to ClinicalTrials.gov's list of Phase 2 midostaurin trials.
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