DGIdb - MIDOSTAURIN Drug Record

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
Drug Type	small molecule
Drug Groups	approved
Drug Groups	investigational
Drug Categories	alkaloids
Drug Categories	antineoplastic agents
Drug Categories	antineoplastic and immunomodulating agents
Drug Categories	carbazoles
Drug Categories	cytochrome p-450 cyp1a2 inducers
Drug Categories	cytochrome p-450 cyp1a2 inducers (strength unknown)
Drug Categories	cytochrome p-450 cyp1a2 inhibitors
Drug Categories	cytochrome p-450 cyp1a2 inhibitors (strong)
Drug Categories	cytochrome p-450 cyp2b6 inducers
Drug Categories	cytochrome p-450 cyp2b6 inducers (strength unknown)
Drug Categories	cytochrome p-450 cyp2c19 inducers
Drug Categories	cytochrome p-450 cyp2c19 inducers (strength unknown)
Drug Categories	cytochrome p-450 cyp2c19 inhibitors
Drug Categories	cytochrome p-450 cyp2c19 inhibitors (weak)
Drug Categories	cytochrome p-450 cyp2c8 inducers
Drug Categories	cytochrome p-450 cyp2c8 inducers (strength unknown)
Drug Categories	cytochrome p-450 cyp2c8 inhibitors
Drug Categories	cytochrome p-450 cyp2c8 inhibitors (strength unknown)
Drug Categories	cytochrome p-450 cyp2c9 inducers
Drug Categories	cytochrome p-450 cyp2c9 inducers (strength unknown)
Drug Categories	cytochrome p-450 cyp2c9 inhibitors
Drug Categories	cytochrome p-450 cyp2c9 inhibitors (strength unknown)
Drug Categories	cytochrome p-450 cyp2d6 inhibitors
Drug Categories	cytochrome p-450 cyp2d6 inhibitors (strong)
Drug Categories	cytochrome p-450 cyp2e1 inhibitors
Drug Categories	cytochrome p-450 cyp2e1 inhibitors (strong)
Drug Categories	cytochrome p-450 cyp3a inducers
Drug Categories	cytochrome p-450 cyp3a inducers (strong)
Drug Categories	cytochrome p-450 cyp3a inhibitors
Drug Categories	cytochrome p-450 cyp3a substrates
Drug Categories	cytochrome p-450 cyp3a4 inducers
Drug Categories	cytochrome p-450 cyp3a4 inducers (strength unknown)
Drug Categories	cytochrome p-450 cyp3a4 inducers (strong)
Drug Categories	cytochrome p-450 cyp3a4 inhibitors
Drug Categories	cytochrome p-450 cyp3a4 inhibitors (strong)
Drug Categories	cytochrome p-450 cyp3a4 substrates
Drug Categories	cytochrome p-450 cyp3a4 substrates with a narrow therapeutic index
Drug Categories	cytochrome p-450 cyp3a5 inducers
Drug Categories	cytochrome p-450 cyp3a5 inducers (strength unknown)
Drug Categories	cytochrome p-450 cyp3a7 inducers
Drug Categories	cytochrome p-450 cyp3a7 inducers (strength unknown)
Drug Categories	cytochrome p-450 enzyme inducers
Drug Categories	cytochrome p-450 enzyme inhibitors
Drug Categories	cytochrome p-450 substrates
Drug Categories	enzyme inhibitors
Drug Categories	heterocyclic compounds, fused-ring
Drug Categories	indole alkaloids
Drug Categories	indoles
Drug Categories	kinase inhibitor
Drug Categories	protein kinase c, antagonists & inhibitors
Drug Categories	protein kinase inhibitors
Drug Categories	receptor tyrosine kinase inhibitors
Drug Categories	tyrosine kinase inhibitors

(13 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.
Chi et al., 2012, ETV6-NTRK3 as a therapeutic target of small molecule inhibitor PKC412., Biochem. Biophys. Res. Commun.
Tognon et al., 2011, ETV6-NTRK3-mediated breast epithelial cell transformation is blocked by targeting the IGF1R signaling pathway., Cancer Res.
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
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 KIT

Interaction Types & Directionality:

inhibitor (inhibitory)

antagonist (inhibitory)

Interaction Info:

Indication/Tumor Type mast-cell leukemia

Response Type predicted – sensitive

Approval Status Preclinical - Patient cell culture

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.

Gotlib et al., 2016, Efficacy and Safety of Midostaurin in Advanced Systemic Mastocytosis., N. Engl. J. Med.

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

MIDOSTAURIN PRKCD

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Protein kinase C (PKC) inhibitor

Publications:
MIDOSTAURIN PRKCZ

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Protein kinase C (PKC) inhibitor

Direct Interaction yes

Publications:
MIDOSTAURIN PRKCE

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Protein kinase C (PKC) inhibitor

Direct Interaction yes

Publications:
MIDOSTAURIN PRKCI

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Protein kinase C (PKC) inhibitor

Direct Interaction yes

Publications:
MIDOSTAURIN PRKCB

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Protein kinase C (PKC) inhibitor

Direct Interaction yes

Publications:
MIDOSTAURIN PRKCQ

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Protein kinase C (PKC) inhibitor

Direct Interaction yes

Publications:
MIDOSTAURIN PRKCG

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Protein kinase C (PKC) inhibitor

Direct Interaction yes

Publications:
MIDOSTAURIN PRKCH

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Protein kinase C (PKC) inhibitor

Direct Interaction yes

Publications:
MIDOSTAURIN PRKD1

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Protein kinase C (PKC) inhibitor

Direct Interaction yes

Publications:
MIDOSTAURIN PRKD3

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Protein kinase C (PKC) inhibitor

Direct Interaction yes

Publications:

MIDOSTAURIN FLT3

Interaction Types & Directionality:

inhibitor (inhibitory)

antagonist (inhibitory)

Interaction Info:

Drug family Pan-TK inhibitor

Alteration FLT3:D835.

Alteration FLT3:N676.

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.

MIDOSTAURIN KDR

Interaction Types & Directionality:

inhibitor (inhibitory)

antagonist (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Vascular endothelial growth factor receptor 2 inhibitor

Publications:

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
MIDOSTAURIN PRKCA

Interaction Types & Directionality:

inhibitor (inhibitory)

antagonist (inhibitory)

Interaction Info:

Mechanism of Interaction Protein kinase C (PKC) inhibitor

Direct Interaction yes

Publications:

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
MIDOSTAURIN PDGFRA

Interaction Types & Directionality:

inhibitor (inhibitory)

antagonist (inhibitory)

Interaction Info:

Mechanism of Interaction Platelet-derived growth factor receptor inhibitor

Direct Interaction yes

Publications:

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
MIDOSTAURIN PDGFRB

Interaction Types & Directionality:

inhibitor (inhibitory)

antagonist (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Platelet-derived growth factor receptor inhibitor

Publications:

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
MIDOSTAURIN KRAS

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Midostaurin + SCH772984

Indication/Tumor Type pancreatic ductal adenocarcinoma

Response Type sensitive

Publications:

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
MIDOSTAURIN ETV6

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type cancer

Response Type sensitive

Approval Status Preclinical

Publications:

Chi et al., 2012, ETV6-NTRK3 as a therapeutic target of small molecule inhibitor PKC412., Biochem. Biophys. Res. Commun.
MIDOSTAURIN PIK3CB

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

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.

MIDOSTAURIN FGFR1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

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.

MIDOSTAURIN NTRK3

Interaction Types & Directionality:

n/a

Interaction Info:

Drug family Pan-TK inhibitor

Alteration NTRK3__.

Publications:

Chi et al., 2012, ETV6-NTRK3 as a therapeutic target of small molecule inhibitor PKC412., Biochem. Biophys. Res. Commun.

Tognon et al., 2011, ETV6-NTRK3-mediated breast epithelial cell transformation is blocked by targeting the IGF1R signaling pathway., Cancer Res.

MIDOSTAURIN PIK3CA

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

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.
MIDOSTAURIN HSPA4

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

Sharkey et al., 2007, PKC412 demonstrates JNK-dependent activity against human multiple myeloma cells., Blood
MIDOSTAURIN STK32B

Interaction Types & Directionality:

n/a

Interaction 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
MIDOSTAURIN NPM1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:
MIDOSTAURIN YES1

Interaction Types & Directionality:

n/a

Interaction Info:

Publications:

DrugBank: DB06595

Version: 5.1.7

Alternate Names:

MIDOSTAURIN DrugBank Drug Name

120685-11-2 CAS Number

Rydapt Drug Brand

Drug Info:

Drug Type small molecule

Drug Groups approved

Drug Groups investigational

Publications:

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

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.

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

CGI: Midostaurin

Version: 27-September-2017

Alternate Names:

Drug Info:

Publications:

Tognon et al., 2011, ETV6-NTRK3-mediated breast epithelial cell transformation is blocked by targeting the IGF1R signaling pathway., Cancer Res.

Chi et al., 2012, ETV6-NTRK3 as a therapeutic target of small molecule inhibitor PKC412., Biochem. Biophys. Res. Commun.

DoCM: PKC412

Version: 27-September-2017

Alternate Names:

Drug Info:

Publications:

Zhang et al., 2014, Reversal of acquired drug resistance in FLT3-mutated acute myeloid leukemia cells via distinct drug combination strategies., Clin. Cancer Res.

Smith et al., 2012, Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia., Nature

Smith et al., 2013, Activity of ponatinib against clinically-relevant AC220-resistant kinase domain mutants of FLT3-ITD., Blood

DoCM: MIDOSTAURIN

Version: 27-September-2017

Alternate Names:

Drug Info:

Publications:

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.

Smith et al., 2012, Validation of ITD mutations in FLT3 as a therapeutic target in human acute myeloid leukaemia., Nature

Jourdan et al., 2013, Prospective evaluation of gene mutations and minimal residual disease in patients with core binding factor acute myeloid leukemia., 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.

Stone et al., 2017, Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation., N. Engl. J. Med.

GuideToPharmacology: 178102329
- Version: 29-September-2020
Alternate Names:

MIDOSTAURIN GuideToPharmacology Ligand Name

Drug Info:

Publications:
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:

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

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

Drug family	Pan-TK inhibitor
Alteration	FLT3:D835.
Alteration	FLT3:N676.

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

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

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

Indication/Tumor Type	cancer
Response Type	sensitive
Approval Status	Preclinical

MIDOSTAURIN	DrugBank Drug Name
120685-11-2	CAS Number
Rydapt	Drug Brand

MIDOSTAURIN Drug Record

MIDOSTAURIN chembl:CHEMBL608533 ApprovedAntineoplastic

Alternate Names:

Drug Info:

Publications:

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

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

Interaction Types & Directionality: inhibitor (inhibitory)

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

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

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

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

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

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

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

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

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

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

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

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

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

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

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

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

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

Publications:

Interaction Types & Directionality: inhibitor (inhibitory)

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

Publications:

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

Interaction Info: Drug family Pan-TK inhibitor Alteration FLT3:D835. Alteration FLT3:N676.

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

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

Publications: 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

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

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

Publications: 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

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

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

Publications: 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

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

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

Publications: 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

Interaction Types & Directionality: n/a

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

Publications: 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

Interaction Types & Directionality: n/a

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

Publications: Chi et al., 2012, ETV6-NTRK3 as a therapeutic target of small molecule inhibitor PKC412., Biochem. Biophys. Res. Commun.

Interaction Types & Directionality: n/a

Interaction Info:

Publications: 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.

Interaction Types & Directionality: n/a

Interaction Info:

Publications: 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.

Interaction Types & Directionality: n/a

Interaction Info: Drug family Pan-TK inhibitor Alteration NTRK3__.

Publications: Chi et al., 2012, ETV6-NTRK3 as a therapeutic target of small molecule inhibitor PKC412., Biochem. Biophys. Res. Commun. Tognon et al., 2011, ETV6-NTRK3-mediated breast epithelial cell transformation is blocked by targeting the IGF1R signaling pathway., Cancer Res.

Interaction Types & Directionality: n/a

Interaction Info:

Publications: 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.

Interaction Types & Directionality: n/a

Interaction Info:

Publications: Sharkey et al., 2007, PKC412 demonstrates JNK-dependent activity against human multiple myeloma cells., Blood

Interaction Types & Directionality: n/a

Interaction 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

Interaction Types & Directionality: n/a

Interaction Info:

Publications:

Interaction Types & Directionality: n/a

Interaction Info:

Interaction Types & Directionality:

inhibitor (inhibitory)

antagonist (inhibitory)

Interaction Info:

Indication/Tumor Type mast-cell leukemia

Response Type predicted – sensitive

Approval Status Preclinical - Patient cell culture

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Protein kinase C (PKC) inhibitor

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Protein kinase C (PKC) inhibitor

Direct Interaction yes

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Protein kinase C (PKC) inhibitor

Direct Interaction yes

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Protein kinase C (PKC) inhibitor

Direct Interaction yes

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Protein kinase C (PKC) inhibitor

Direct Interaction yes

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Protein kinase C (PKC) inhibitor

Direct Interaction yes

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Protein kinase C (PKC) inhibitor

Direct Interaction yes

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Protein kinase C (PKC) inhibitor

Direct Interaction yes

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Protein kinase C (PKC) inhibitor

Direct Interaction yes

Interaction Types & Directionality:

inhibitor (inhibitory)

Interaction Info:

Mechanism of Interaction Protein kinase C (PKC) inhibitor

Direct Interaction yes

Interaction Types & Directionality:

inhibitor (inhibitory)

antagonist (inhibitory)

Interaction Info:

Drug family Pan-TK inhibitor

Alteration FLT3:D835.

Alteration FLT3:N676.

Interaction Types & Directionality:

inhibitor (inhibitory)

antagonist (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Vascular endothelial growth factor receptor 2 inhibitor

Publications:

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

Interaction Types & Directionality:

inhibitor (inhibitory)

antagonist (inhibitory)

Interaction Info:

Mechanism of Interaction Protein kinase C (PKC) inhibitor

Direct Interaction yes

Publications:

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

Interaction Types & Directionality:

inhibitor (inhibitory)

antagonist (inhibitory)

Interaction Info:

Mechanism of Interaction Platelet-derived growth factor receptor inhibitor

Direct Interaction yes

Publications:

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

Interaction Types & Directionality:

inhibitor (inhibitory)

antagonist (inhibitory)

Interaction Info:

Direct Interaction yes

Mechanism of Interaction Platelet-derived growth factor receptor inhibitor

Publications:

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

Interaction Types & Directionality:

n/a

Interaction Info:

combination therapy Midostaurin + SCH772984

Indication/Tumor Type pancreatic ductal adenocarcinoma

Response Type sensitive

Publications:

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

Interaction Types & Directionality:

n/a

Interaction Info:

Indication/Tumor Type cancer

Response Type sensitive

Approval Status Preclinical

Publications:

Chi et al., 2012, ETV6-NTRK3 as a therapeutic target of small molecule inhibitor PKC412., Biochem. Biophys. Res. Commun.

Interaction Types & Directionality:

n/a

Publications:

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.

Interaction Types & Directionality:

n/a

Publications:

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.

Interaction Types & Directionality:

n/a

Interaction Info:

Drug family Pan-TK inhibitor

Alteration NTRK3__.

Publications:

Chi et al., 2012, ETV6-NTRK3 as a therapeutic target of small molecule inhibitor PKC412., Biochem. Biophys. Res. Commun.

Tognon et al., 2011, ETV6-NTRK3-mediated breast epithelial cell transformation is blocked by targeting the IGF1R signaling pathway., Cancer Res.

Interaction Types & Directionality:

n/a

Publications:

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.

Interaction Types & Directionality:

n/a

Publications:

Sharkey et al., 2007, PKC412 demonstrates JNK-dependent activity against human multiple myeloma cells., Blood

Interaction Types & Directionality:

n/a

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

Interaction Types & Directionality:

n/a

Interaction Types & Directionality:

n/a

Alternate Names:

MIDOSTAURIN DrugBank Drug Name

120685-11-2 CAS Number

Rydapt Drug Brand

Drug Info:

Drug Type small molecule

Drug Groups approved

Drug Groups investigational

Publications:

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

Alternate Names:

MIDOSTAURIN Generic Name

Drug Info:

Drug Class Kinase Inhibitors

Drug Info:

Drug Indications antineoplastic agent

Drug Class Small molecule

FDA Approval not approved

Alternate Names:

C1872 NCI drug code

Alternate Names:

CHEMBL608533 ChEMBL Drug ID

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

Publications:

Tognon et al., 2011, ETV6-NTRK3-mediated breast epithelial cell transformation is blocked by targeting the IGF1R signaling pathway., Cancer Res.

Chi et al., 2012, ETV6-NTRK3 as a therapeutic target of small molecule inhibitor PKC412., Biochem. Biophys. Res. Commun.