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MIDOSTAURIN Drug Record

  • Summary
  • Interactions
  • Claims
  • MIDOSTAURIN chembl:CHEMBL608533 ApprovedAntineoplastic

    Alternate Names:

    PKC-412
    CGP-41251
    NVP-PKC412
    MIDOSTAURIN
    RYDAPT
    PKC412
    BENZOYLSTAUROSPORINE
    4'-N-BENZOYLSTAUROSPORINE
    CGP 41251
    N-BENZOYLSTAUROSPORINE
    PKC 412
    CGP 41231
    drugbank:06595
    chembl:CHEMBL608533
    pubchem.compound:9829523
    chemidplus:120685-11-2
    rxcui:1919083

    Drug Info:

    Drug Class Kinase Inhibitors
    FDA Approval not approved
    Drug Class Small molecule
    Drug Indications antineoplastic agent
    (10 More Sources)

    Publications:

    Albers et al., 2013, The secondary FLT3-ITD F691L mutation induces resistance to AC220 in FLT3-ITD+ AML but retains in vitro sensitivity to PKC412 and Sunitinib., Leukemia
    Strati et al., 2015, Phase I/II trial of the combination of midostaurin (PKC412) and 5-azacytidine for patients with acute myeloid leukemia and myelodysplastic syndrome., Am. J. Hematol.
    Stone et al., 2017, Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation., N. Engl. J. Med.
    Fröhling et al., 2007, Identification of driver and passenger mutations of FLT3 by high-throughput DNA sequence analysis and functional assessment of candidate alleles., Cancer Cell
    Weisberg et al., 2002, Inhibition of mutant FLT3 receptors in leukemia cells by the small molecule tyrosine kinase inhibitor PKC412., Cancer Cell
    Stone et al., 2012, Phase IB study of the FLT3 kinase inhibitor midostaurin with chemotherapy in younger newly diagnosed adult patients with acute myeloid leukemia., Leukemia
    Kindler et al., 2005, Identification of a novel activating mutation (Y842C) within the activation loop of FLT3 in patients with acute myeloid leukemia (AML)., Blood
    Kancha et al., 2007, Sensitivity toward sorafenib and sunitinib varies between different activating and drug-resistant FLT3-ITD mutations., Exp. Hematol.
    Wang et al., 2012, MicroRNAs in liver disease., Gastroenterology
    Piloto et al., 2007, Prolonged exposure to FLT3 inhibitors leads to resistance via activation of parallel signaling pathways., Blood
    Mathews et al., 2007, Impact of FLT3 mutations and secondary cytogenetic changes on the outcome of patients with newly diagnosed acute promyelocytic leukemia treated with a single agent arsenic trioxide regimen., Haematologica
    Zimmerman et al., 2013, Crenolanib is active against models of drug-resistant FLT3-ITD-positive acute myeloid leukemia., Blood
    Bagrintseva et al., 2004, Mutations in the tyrosine kinase domain of FLT3 define a new molecular mechanism of acquired drug resistance to PTK inhibitors in FLT3-ITD-transformed hematopoietic cells., Blood
    Smith et al., 2013, Activity of ponatinib against clinically-relevant AC220-resistant kinase domain mutants of FLT3-ITD., Blood
    Yamamoto et al., 2001, Activating mutation of D835 within the activation loop of FLT3 in human hematologic malignancies., Blood
    MacConaill et al., 2014, Prospective enterprise-level molecular genotyping of a cohort of cancer patients., J Mol Diagn
    Mardis et al., 2009, Recurring mutations found by sequencing an acute myeloid leukemia genome., N. Engl. J. Med.
    Martelli et al., 2013, Mutational landscape of AML with normal cytogenetics: biological and clinical implications., Blood Rev.
    Allen et al., 2013, The importance of relative mutant level for evaluating impact on outcome of KIT, FLT3 and CBL mutations in core-binding factor acute myeloid leukemia., Leukemia
    Knapper et al., 2006, A phase 2 trial of the FLT3 inhibitor lestaurtinib (CEP701) as first-line treatment for older patients with acute myeloid leukemia not considered fit for intensive chemotherapy., Blood
    Man et al., 2012, Sorafenib treatment of FLT3-ITD(+) acute myeloid leukemia: favorable initial outcome and mechanisms of subsequent nonresponsiveness associated with the emergence of a D835 mutation., Blood
    Brown et al., 2005, FLT3 inhibition selectively kills childhood acute lymphoblastic leukemia cells with high levels of FLT3 expression., Blood
    Eisenhoffer et al., 2012, Crowding induces live cell extrusion to maintain homeostatic cell numbers in epithelia., Nature
    Clark et al., 2004, Variable sensitivity of FLT3 activation loop mutations to the small molecule tyrosine kinase inhibitor MLN518., Blood
    Smith et al., 2013, The role of kinase inhibitors in the treatment of patients with acute myeloid leukemia., Am Soc Clin Oncol Educ Book
    Jourdan et al., 2013, Prospective evaluation of gene mutations and minimal residual disease in patients with core binding factor acute myeloid leukemia., Blood
    Smith et al., 2012, Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia., Nature
    Fischer et al., 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., J. Clin. Oncol.
    Levis, 2017, Midostaurin approved for FLT3-mutated AML., Blood
    Opatz et al., 2013, Exome sequencing identifies recurring FLT3 N676K mutations in core-binding factor leukemia., Blood
    Zhang et al., 2014, Reversal of acquired drug resistance in FLT3-mutated acute myeloid leukemia cells via distinct drug combination strategies., Clin. Cancer Res.
    Cools et al., 2004, Prediction of resistance to small molecule FLT3 inhibitors: implications for molecularly targeted therapy of acute leukemia., Cancer Res.
    Heidel et al., 2006, Clinical resistance to the kinase inhibitor PKC412 in acute myeloid leukemia by mutation of Asn-676 in the FLT3 tyrosine kinase domain., Blood
    Jiang J et al., 2004, Identifying and characterizing a novel activating mutation of the FLT3 tyrosine kinase in AML., Blood
    Williams AB et al., 2013, Mutations of FLT3/ITD confer resistance to multiple tyrosine kinase inhibitors., Leukemia
    Millward MJ et al., 2006, The multikinase inhibitor midostaurin (PKC412A) lacks activity in metastatic melanoma: a phase IIA clinical and biologic study., Br J Cancer
    Gallogly MM et al., 2016, Midostaurin: an emerging treatment for acute myeloid leukemia patients., J Blood Med
    Valent et al., 2015, Chronic mast cell leukemia (MCL) with KIT S476I: a rare entity defined by leukemic expansion of mature mast cells and absence of organ damage., Ann. Hematol.
    Gotlib et al., 2016, Efficacy and Safety of Midostaurin in Advanced Systemic Mastocytosis., N. Engl. J. Med.
    Tenzer et al., 2001, The phosphatidylinositide 3'-kinase/Akt survival pathway is a target for the anticancer and radiosensitizing agent PKC412, an inhibitor of protein kinase C., Cancer Res.
    Chen et al., 2004, PKC412 inhibits the zinc finger 198-fibroblast growth factor receptor 1 fusion tyrosine kinase and is active in treatment of stem cell myeloproliferative disorder., Proc. Natl. Acad. Sci. U.S.A.
    Sharkey et al., 2007, PKC412 demonstrates JNK-dependent activity against human multiple myeloma cells., Blood
    Hayes et al., 2016, Long-Term ERK Inhibition in KRAS-Mutant Pancreatic Cancer Is Associated with MYC Degradation and Senescence-like Growth Suppression., Cancer Cell
    Chi et al., 2012, ETV6-NTRK3 as a therapeutic target of small molecule inhibitor PKC412., Biochem. Biophys. Res. Commun.
    Jester BW et al., 2012, Testing the promiscuity of commercial kinase inhibitors against the AGC kinase group using a split-luciferase screen., J Med Chem
  • MIDOSTAURIN   STK32B

    Interaction Score: 4.95

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    22257127


    Sources:
    DTC

  • MIDOSTAURIN   FLT3

    Interaction Score: 1.37

    Interaction Types & Directionality:
    antagonist (inhibitory)
    inhibitor (inhibitory)

    Interaction Info:
    Approval Status Phase III
    Response Type resistant
    combination therapy Azacitidine + Midostaurin

    PMIDs:
    23392356 25530214 28644114 18068628 12124173 22627678 15345593 17889720 22504185 17047150 17606455 24046014 14604974 23430109 11290608 25157968 19657110 23261068 23783394 16857985 22368270 15374878 22504183 15256420 23714533 23321257 22504184 20733134 28546144 23878140 24619500 15374944 16150941 15178581 22858906 16969355 27186148


    Sources:
    MyCancerGenome TdgClinicalTrial JAX-CKB ChemblInteractions DoCM CIViC PharmGKB TTD FDA OncoKB

  • MIDOSTAURIN   ETV6

    Interaction Score: 0.41

    Interaction Types & Directionality:
    n/a

    Interaction Info:
    Indication/Tumor Type cancer
    Response Type sensitive
    Approval Status Preclinical

    PMIDs:
    23131561


    Sources:
    JAX-CKB

  • MIDOSTAURIN   PRKCA

    Interaction Score: 0.39

    Interaction Types & Directionality:
    antagonist (inhibitory)
    inhibitor (inhibitory)

    Interaction Info:
    Mechanism of Interaction Protein kinase C (PKC) inhibitor
    Direct Interaction yes

    PMIDs:
    16969355


    Sources:
    MyCancerGenome ChemblInteractions

  • MIDOSTAURIN   KIT

    Interaction Score: 0.36

    Interaction Types & Directionality:
    antagonist (inhibitory)
    inhibitor (inhibitory)

    Interaction Info:
    Indication/Tumor Type mast-cell leukemia
    Response Type predicted – sensitive
    Approval Status Preclinical - Patient cell culture

    PMIDs:
    25209843 27355533 16969355


    Sources:
    MyCancerGenome JAX-CKB ChemblInteractions CIViC PharmGKB FDA

  • MIDOSTAURIN   PRKCH

    Interaction Score: 0.35

    Interaction Types & Directionality:
    inhibitor (inhibitory)

    Interaction Info:
    Mechanism of Interaction Protein kinase C (PKC) inhibitor
    Direct Interaction yes

    PMIDs:
    None found


    Sources:
    ChemblInteractions

  • MIDOSTAURIN   NPM1

    Interaction Score: 0.35

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    None found


    Sources:
    PharmGKB FDA

  • MIDOSTAURIN   PRKD1

    Interaction Score: 0.27

    Interaction Types & Directionality:
    inhibitor (inhibitory)

    Interaction Info:
    Mechanism of Interaction Protein kinase C (PKC) inhibitor
    Direct Interaction yes

    PMIDs:
    None found


    Sources:
    ChemblInteractions

  • MIDOSTAURIN   PRKCI

    Interaction Score: 0.27

    Interaction Types & Directionality:
    inhibitor (inhibitory)

    Interaction Info:
    Mechanism of Interaction Protein kinase C (PKC) inhibitor
    Direct Interaction yes

    PMIDs:
    None found


    Sources:
    ChemblInteractions

  • MIDOSTAURIN   PRKCG

    Interaction Score: 0.24

    Interaction Types & Directionality:
    inhibitor (inhibitory)

    Interaction Info:
    Mechanism of Interaction Protein kinase C (PKC) inhibitor
    Direct Interaction yes

    PMIDs:
    None found


    Sources:
    ChemblInteractions TTD

  • MIDOSTAURIN   PRKCZ

    Interaction Score: 0.22

    Interaction Types & Directionality:
    inhibitor (inhibitory)

    Interaction Info:
    Mechanism of Interaction Protein kinase C (PKC) inhibitor
    Direct Interaction yes

    PMIDs:
    None found


    Sources:
    ChemblInteractions

  • MIDOSTAURIN   PRKCE

    Interaction Score: 0.21

    Interaction Types & Directionality:
    inhibitor (inhibitory)

    Interaction Info:
    Mechanism of Interaction Protein kinase C (PKC) inhibitor
    Direct Interaction yes

    PMIDs:
    None found


    Sources:
    ChemblInteractions

  • MIDOSTAURIN   PRKCB

    Interaction Score: 0.19

    Interaction Types & Directionality:
    inhibitor (inhibitory)

    Interaction Info:
    Mechanism of Interaction Protein kinase C (PKC) inhibitor
    Direct Interaction yes

    PMIDs:
    None found


    Sources:
    ChemblInteractions

  • MIDOSTAURIN   HSPA4

    Interaction Score: 0.16

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    17032922


    Sources:
    NCI

  • MIDOSTAURIN   PRKCQ

    Interaction Score: 0.15

    Interaction Types & Directionality:
    inhibitor (inhibitory)

    Interaction Info:
    Mechanism of Interaction Protein kinase C (PKC) inhibitor
    Direct Interaction yes

    PMIDs:
    None found


    Sources:
    ChemblInteractions

  • MIDOSTAURIN   PDGFRA

    Interaction Score: 0.12

    Interaction Types & Directionality:
    antagonist (inhibitory)
    inhibitor (inhibitory)

    Interaction Info:
    Mechanism of Interaction Platelet-derived growth factor receptor inhibitor
    Direct Interaction yes

    PMIDs:
    16969355


    Sources:
    MyCancerGenome ChemblInteractions

  • MIDOSTAURIN   PIK3CB

    Interaction Score: 0.1

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    11719451


    Sources:
    NCI

  • MIDOSTAURIN   PRKCD

    Interaction Score: 0.08

    Interaction Types & Directionality:
    inhibitor (inhibitory)

    Interaction Info:
    Direct Interaction yes
    Mechanism of Interaction Protein kinase C (PKC) inhibitor

    PMIDs:
    None found


    Sources:
    ChemblInteractions

  • MIDOSTAURIN   PDGFRB

    Interaction Score: 0.07

    Interaction Types & Directionality:
    antagonist (inhibitory)
    inhibitor (inhibitory)

    Interaction Info:
    Direct Interaction yes
    Mechanism of Interaction Platelet-derived growth factor receptor inhibitor

    PMIDs:
    16969355


    Sources:
    ChemblInteractions

  • MIDOSTAURIN   PRKD3

    Interaction Score: 0.07

    Interaction Types & Directionality:
    inhibitor (inhibitory)

    Interaction Info:
    Mechanism of Interaction Protein kinase C (PKC) inhibitor
    Direct Interaction yes

    PMIDs:
    None found


    Sources:
    ChemblInteractions

  • MIDOSTAURIN   KDR

    Interaction Score: 0.06

    Interaction Types & Directionality:
    antagonist (inhibitory)
    inhibitor (inhibitory)

    Interaction Info:
    Direct Interaction yes
    Mechanism of Interaction Vascular endothelial growth factor receptor 2 inhibitor

    PMIDs:
    16969355


    Sources:
    MyCancerGenome ChemblInteractions

  • MIDOSTAURIN   FGFR1

    Interaction Score: 0.06

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    15448205


    Sources:
    CIViC

  • MIDOSTAURIN   KRAS

    Interaction Score: 0.04

    Interaction Types & Directionality:
    n/a

    Interaction Info:
    combination therapy Midostaurin + SCH772984
    Indication/Tumor Type pancreatic ductal adenocarcinoma
    Response Type sensitive

    PMIDs:
    26725216


    Sources:
    JAX-CKB

  • MIDOSTAURIN   PIK3CA

    Interaction Score: 0.04

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    11719451


    Sources:
    NCI

  • MIDOSTAURIN   YES1

    Interaction Score: 0.01

    Interaction Types & Directionality:
    n/a

    Interaction Info:

    PMIDs:
    None found


    Sources:
    DTC

  • MyCancerGenome: MIDOSTAURIN

    • Version: 20-Jun-2017

    Alternate Names:
    MIDOSTAURIN Generic Name

    Drug Info:
    Drug Class Kinase Inhibitors

    Publications:

  • TdgClinicalTrial: MIDOSTAURIN

    • Version: January-2014

    Alternate Names:

    Drug Info:
    Drug Indications antineoplastic agent
    Drug Class Small molecule
    FDA Approval not approved

    Publications:

  • NCI: PKC412

    • Version: 14-September-2017

    Alternate Names:
    C1872 NCI drug code

    Drug Info:

    Publications:
    Sharkey et al., 2007, PKC412 demonstrates JNK-dependent activity against human multiple myeloma cells., Blood
    Tenzer et al., 2001, The phosphatidylinositide 3'-kinase/Akt survival pathway is a target for the anticancer and radiosensitizing agent PKC412, an inhibitor of protein kinase C., Cancer Res.

  • DTC: MIDOSTAURIN

    • Version: 02-September-2020

    Alternate Names:
    CHEMBL608533 ChEMBL Drug ID

    Drug Info:

    Publications:
    Jester BW et al., 2012, Testing the promiscuity of commercial kinase inhibitors against the AGC kinase group using a split-luciferase screen., J Med Chem

  • JAX-CKB: Midostaurin

    • Version: 27-September-2017

    Alternate Names:

    Drug Info:

    Publications:
    Valent et al., 2015, Chronic mast cell leukemia (MCL) with KIT S476I: a rare entity defined by leukemic expansion of mature mast cells and absence of organ damage., Ann. Hematol.
    Chi et al., 2012, ETV6-NTRK3 as a therapeutic target of small molecule inhibitor PKC412., Biochem. Biophys. Res. Commun.
    Stone et al., 2012, Phase IB study of the FLT3 kinase inhibitor midostaurin with chemotherapy in younger newly diagnosed adult patients with acute myeloid leukemia., Leukemia

  • DoCM: PKC412

    • Version: 27-September-2017

    Alternate Names:

    Drug Info:

    Publications:
    Smith et al., 2013, Activity of ponatinib against clinically-relevant AC220-resistant kinase domain mutants of FLT3-ITD., Blood
    Smith et al., 2012, Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia., Nature
    Zhang et al., 2014, Reversal of acquired drug resistance in FLT3-mutated acute myeloid leukemia cells via distinct drug combination strategies., Clin. Cancer Res.

  • DoCM: MIDOSTAURIN

    • Version: 27-September-2017

    Alternate Names:

    Drug Info:

    Publications:
    Kancha et al., 2007, Sensitivity toward sorafenib and sunitinib varies between different activating and drug-resistant FLT3-ITD mutations., Exp. Hematol.
    Mardis et al., 2009, Recurring mutations found by sequencing an acute myeloid leukemia genome., N. Engl. J. Med.
    Knapper et al., 2006, A phase 2 trial of the FLT3 inhibitor lestaurtinib (CEP701) as first-line treatment for older patients with acute myeloid leukemia not considered fit for intensive chemotherapy., Blood

  • CIViC: MIDOSTAURIN

    • Version: 14-September-2020

    Alternate Names:

    Drug Info:

    Publications:
    Gotlib et al., 2016, Efficacy and Safety of Midostaurin in Advanced Systemic Mastocytosis., N. Engl. J. Med.
    Chen et al., 2004, PKC412 inhibits the zinc finger 198-fibroblast growth factor receptor 1 fusion tyrosine kinase and is active in treatment of stem cell myeloproliferative disorder., Proc. Natl. Acad. Sci. U.S.A.
    Jiang J et al., 2004, Identifying and characterizing a novel activating mutation of the FLT3 tyrosine kinase in AML., Blood

  • TTD: Midostaurin

    • Version: 2020.06.01

    Alternate Names:
    D07NVU TTD Drug ID

    Drug Info:

    Publications:

  • ChemblDrugs: chembl:CHEMBL608533

    • Version: ChEMBL_27

    Alternate Names:

    Drug Info:

    Publications:

  • ChemblInteractions: CHEMBL608533

    • Version: chembl_23

    Alternate Names:

    Drug Info:

    Publications:

  • PharmGKB: midostaurin

    • Version: 18-August-2020

    Alternate Names:

    Drug Info:

    Publications:

  • OncoKB: Midostaurin

    • Version: 23-July-2020

    Alternate Names:

    Drug Info:

    Publications:

  • FDA: Midostaurin

    • Version: 04-September-2020

    Alternate Names:

    Drug Info:

    Publications:

Disclaimer: This resource is intended for purely research purposes. It should not be used for emergencies or medical or professional advice.

A finding of a drug-gene interaction or potentially druggable category does not necessarily indicate effectiveness (or lack thereof) of any drug or treatment regimen. A finding of no interaction or no potentially druggable category does not necessarily indicate lack of effectiveness of any drug or treatment regimen. Drug-gene interactions or potentially druggable categories are not presented in ranked order of potential or predicted efficacy.

The dgidb.org website does not provide any medical or healthcare products, services or advice, and is not for medical emergencies or urgent situations. IF YOU THINK YOU MAY HAVE A MEDICAL EMERGENCY, CALL YOUR DOCTOR OR 911 IMMEDIATELY. Information contained on this website is not a substitute for a doctor's medical judgment or advice. We recommend that you discuss your specific, individual health concerns with your doctor or health care professional.

DGIdb (v4.2.0 - sha1 afd9f30b) • Last updated 2020-10-21