Midostaurin

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Midostaurin
Midostaurin skeletal.svg
Ball-and-stick model of the midostaurin molecule
Systematic (IUPAC) name
(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
Clinical data
  • Investigational
Oral
Identifiers
120685-11-2
None
PubChem CID 9829523
ChemSpider 8005258
UNII ID912S5VON YesY
ChEMBL CHEMBL608533
Synonyms 4'-N-benzoylstaurosporine
Chemical data
Formula C35H30N4O4
570.637 g/mol

Midostaurin (PKC412) is a multi-target protein kinase inhibitor being investigated for the treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). It is a semi-synthetic derivative of staurosporine, an alkaloid from the bacterium Streptomyces staurosporeus, and is active in patients with mutations of CD135 (FMS-like tyrosine kinase 3 receptor, FLT3).[1]

After successful Phase II clinical trials, a Phase III trial for AML has started in 2008. It is testing midostaurin in combination with daunorubicin and cytarabine.[2] In another trial, the substance has proven ineffective in metastatic melanoma.[3]

References[edit]

  1. ^ Fischer, T.; Stone, R. M.; Deangelo, D. J.; Galinsky, I.; Estey, E.; Lanza, C.; Fox, E.; Ehninger, G.; Feldman, E. J.; Schiller, G. J.; Klimek, V. M.; Nimer, S. D.; Gilliland, D. G.; Dutreix, C.; Huntsman-Labed, A.; Virkus, J.; Giles, F. J. (2010). "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". Journal of Clinical Oncology 28 (28): 4339–4345. doi:10.1200/JCO.2010.28.9678. PMID 20733134.  edit
  2. ^ Clinical trial number NCT00651261 for "Daunorubicin, Cytarabine, and Midostaurin in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia" at ClinicalTrials.gov
  3. ^ Millward, M. J.; House, C.; Bowtell, D.; Webster, L.; Olver, I. N.; Gore, M.; Copeman, M.; Lynch, K.; Yap, A.; Wang, Y.; Cohen, P. S.; Zalcberg, J. (2006). "The multikinase inhibitor midostaurin (PKC412A) lacks activity in metastatic melanoma: a phase IIA clinical and biologic study". British Journal of Cancer 95 (7): 829–834. doi:10.1038/sj.bjc.6603331. PMC 2360547. PMID 16969355.  edit