Art. -Nr.: HY-10230

Midostaurin

(Synonyms: PKC412; CGP 41251)

39 Cited Publications

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Based on 39 publication(s) in Google Scholar

Midostaurin (PKC412; CGP 41251) is an orally active, reversible multi-targeted protein kinase inhibitor. Midostaurin inhibits PKCα/β/γ, Syk, Flk-1, Akt, PKA, c-Kit, c-Fgr, c-Src, FLT3, PDFRβ and VEGFR1/2 with IC₅₀s ranging from 22-500 nM. Midostaurin also upregulates endothelial nitric oxide synthase (eNOS) gene expression. Midostaurin shows powerful anticancer effects.

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Reinheit: 99.81%
CAS. Nr.: 120685-11-2
Formel: C₃₅H₃₀N₄O₄
Molecular Weight:570.64

Speicherung:

-20°C, sealed storage, away from moisture

* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

Midostaurin Chemical Structure

CAS. Nr.: 120685-11-2

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Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
- Clinical Trial
Chemical Information
Publications (39)
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- In Vivo
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Biologische Aktivität

Beschreibung

Midostaurin (PKC412; CGP 41251) is an orally active, reversible multi-targeted protein kinase inhibitor. Midostaurin inhibits PKCα/β/γ, Syk, Flk-1, Akt, PKA, c-Kit, c-Fgr, c-Src, FLT3, PDFRβ and VEGFR1/2 with IC₅₀s ranging from 22-500 nM^[1]^[2]. Midostaurin also upregulates endothelial nitric oxide synthase (eNOS) gene expression. Midostaurin shows powerful anticancer effects^[3].

IC₅₀ & Target^[2]

cPKC-α

22 nM (IC₅₀)

eNOS

cPKC-γ

24 nM (IC₅₀)

cPKC-β1

30 nM (IC₅₀)

cPKC-β2

31 nM (IC₅₀)

nPKC-δ

33 nM (IC₅₀)

nPKC-η

160 nM (IC₅₀)

nPKC-ε

1250 nM (IC₅₀)

aPKC-ζ

465000 nM (IC₅₀)

PPK

38 nM (IC₅₀)

KDR

86 nM (IC₅₀)

c-Syk

95 nM (IC₅₀)

cdk1/cycB

570 nM (IC₅₀)

Protein kinase A

570 nM (IC₅₀)

c-Fgr

790 nM (IC₅₀)

c-Src

800 nM (IC₅₀)

Flt-1

912 nM (IC₅₀)

EGF-R

1100 nM (IC₅₀)

Myosin-light chain kinase

1900 nM (IC₅₀)

Flk-1

3900 nM (IC₅₀)

c-Lyn

4300 nM (IC₅₀)

P70S6 kinase

5000 nM (IC₅₀)

CSK

8000 nM (IC₅₀)

Alle PKC Isoform-spezifische Produkte anzeigen :

Alle VEGFR Isoform-spezifische Produkte anzeigen :

Alle NO Synthase Isoform-spezifische Produkte anzeigen :

Cellular Effect

Cell Line	Type	Value	Description	References
A-375	IC₅₀	180 nM Compound: PKC-412	Toxicity against human A375 cells after 72 hrs by cell titer-blue assay Toxicity against human A375 cells after 72 hrs by cell titer-blue assay	[PMID: 19654408]
BaF3	IC₅₀	200 nM Compound: PKC412	Antiproliferative activity against mouse BAF3 cells transformed with ZNF198-FGFR1 construct Antiproliferative activity against mouse BAF3 cells transformed with ZNF198-FGFR1 construct	[PMID: 21936542]
BaF3	GI₅₀	16 nM Compound: 4; PKC412	Inhibition of FLT3 D835Y mutant in mouse BAF3 cells assessed as cell growth inhibition after 72 hrs by CellTiter 96 AQueous One Solution Cell Proliferation assay Inhibition of FLT3 D835Y mutant in mouse BAF3 cells assessed as cell growth inhibition after 72 hrs by CellTiter 96 AQueous One Solution Cell Proliferation assay	[PMID: 31721578]
BaF3	GI₅₀	43 nM Compound: 4; PKC412	Inhibition of FLT3 ITD/D835Y double mutant in mouse BAF3 cells assessed as cell growth inhibition after 72 hrs by CellTiter 96 AQueous One Solution Cell Proliferation assay Inhibition of FLT3 ITD/D835Y double mutant in mouse BAF3 cells assessed as cell growth inhibition after 72 hrs by CellTiter 96 AQueous One Solution Cell Proliferation assay	[PMID: 31721578]
BaF3	GI₅₀	47 nM Compound: 4; PKC412	Inhibition of FLT3 ITD/F691L double mutant in mouse BAF3 cells assessed as cell growth inhibition after 72 hrs by CellTiter 96 AQueous One Solution Cell Proliferation assay Inhibition of FLT3 ITD/F691L double mutant in mouse BAF3 cells assessed as cell growth inhibition after 72 hrs by CellTiter 96 AQueous One Solution Cell Proliferation assay	[PMID: 31721578]
BaF3	GI₅₀	540 nM Compound: 4; PKC412	Cytotoxicity against mouse BAF3 assessed as cell growth inhibition after 72 hrs by CellTiter 96 AQueous One Solution Cell Proliferation assay Cytotoxicity against mouse BAF3 assessed as cell growth inhibition after 72 hrs by CellTiter 96 AQueous One Solution Cell Proliferation assay	[PMID: 31721578]
BaF3	IC₅₀	4.14 nM Compound: Midostaurin	Antiproliferative activity against mouse BaF3 FLT3-ITD cells assessed as reduction in cell viability measured after 72 hrs by MTS assay Antiproliferative activity against mouse BaF3 FLT3-ITD cells assessed as reduction in cell viability measured after 72 hrs by MTS assay	[PMID: 32659083]
BaF3	GI₅₀	<10 nM Compound: 1c	Growth inhibition of mouse BAF3 cells harboring FLT3 measured after 72 hrs by CCK8 assay Growth inhibition of mouse BAF3 cells harboring FLT3 measured after 72 hrs by CCK8 assay	[PMID: 35923716]
BaF3	GI₅₀	<100 nM Compound: 1c	Growth inhibition of mouse BAF3 cells measured after 72 hrs by CCK8 assay Growth inhibition of mouse BAF3 cells measured after 72 hrs by CCK8 assay	[PMID: 35923716]
BaF3	IC₅₀	<10 nM Compound: 1c	Induction of apoptosis in mouse BaF3 cells harboring FLT3 ITD mutation measured after 72 hrs by Annexin-V-Fluos Staining Kit analysis Induction of apoptosis in mouse BaF3 cells harboring FLT3 ITD mutation measured after 72 hrs by Annexin-V-Fluos Staining Kit analysis	[PMID: 35923716]
BaF3	IC₅₀	<10 nM Compound: 1c	Induction of cell cycle arrest at G1 phase in mouse BaF3 cells harboring FLT3 ITD assessed as accumulation of cells at G1 phase measured after 72 hrs by flow cytometry method Induction of cell cycle arrest at G1 phase in mouse BaF3 cells harboring FLT3 ITD assessed as accumulation of cells at G1 phase measured after 72 hrs by flow cytometry method	[PMID: 35923716]
BaF3	IC₅₀	0.002 μM Compound: PKC412	Antiproliferative activity against mouse BaF3 cells harboring FLT3 ITD/D835V mutant assessed as inhibition of cell growth incubated for 72 hrs Antiproliferative activity against mouse BaF3 cells harboring FLT3 ITD/D835V mutant assessed as inhibition of cell growth incubated for 72 hrs	[PMID: 37163951]
BaF3	IC₅₀	0.004 μM Compound: PKC412	Antiproliferative activity against mouse BaF3 cells harboring FLT3 D835V mutant assessed as inhibition of cell growth incubated for 72 hrs Antiproliferative activity against mouse BaF3 cells harboring FLT3 D835V mutant assessed as inhibition of cell growth incubated for 72 hrs	[PMID: 37163951]
BaF3	IC₅₀	0.007 μM Compound: PKC412	Antiproliferative activity against mouse BaF3 cells harboring FLT3 ITD/F691L mutant assessed as inhibition of cell growth incubated for 72 hrs Antiproliferative activity against mouse BaF3 cells harboring FLT3 ITD/F691L mutant assessed as inhibition of cell growth incubated for 72 hrs	[PMID: 37163951]
BaF3	IC₅₀	0.011 μM Compound: PKC412	Antiproliferative activity against mouse BaF3 cells harboring FLT3 ITD mutant assessed as inhibition of cell growth incubated for 72 hrs Antiproliferative activity against mouse BaF3 cells harboring FLT3 ITD mutant assessed as inhibition of cell growth incubated for 72 hrs	[PMID: 37163951]
BaF3	IC₅₀	0.076 μM Compound: PKC412	Antiproliferative activity against mouse BaF3 cells harboring FLT3 ITD/N676D mutant assessed as inhibition of cell growth incubated for 72 hrs Antiproliferative activity against mouse BaF3 cells harboring FLT3 ITD/N676D mutant assessed as inhibition of cell growth incubated for 72 hrs	[PMID: 37163951]
BaF3	IC₅₀	0.32 μM Compound: PKC412	Cytotoxicity against mouse BaF3 cells assessed as inhibition of cell growth incubated for 72 hrs Cytotoxicity against mouse BaF3 cells assessed as inhibition of cell growth incubated for 72 hrs	[PMID: 37163951]
EOL1	IC₅₀	0.0038 μM Compound: PKC412	Cytotoxicity against human EOL-1 cells after 72 hrs by MTS assay Cytotoxicity against human EOL-1 cells after 72 hrs by MTS assay	[PMID: 29350920]
GISTT1	GI₅₀	235 nM Compound: 4; PKC412	Antiproliferative activity against human GISTT1 cells harboring heterozygous deletion mutation at C-kit exon 11 assessed as cell growth inhibition after 72 hrs by CellTiter 96 AQueous One Solution Cell Proliferation assay Antiproliferative activity against human GISTT1 cells harboring heterozygous deletion mutation at C-kit exon 11 assessed as cell growth inhibition after 72 hrs by CellTiter 96 AQueous One Solution Cell Proliferation assay	[PMID: 31721578]
HL-60	IC₅₀	>10 μM Compound: PKC-412	Antiproliferative activity against human HL60 cells measured after 72 hrs by Celltiter-Glo assay Antiproliferative activity against human HL60 cells measured after 72 hrs by Celltiter-Glo assay	[PMID: 31361136]
HL-60	IC₅₀	0.5 μM Compound: Midostaurin	Antiproliferative activity against human HL-60 cells expressing wild type FLT3 assessed as reduction in cell viability measured after 72 hrs by MTS assay Antiproliferative activity against human HL-60 cells expressing wild type FLT3 assessed as reduction in cell viability measured after 72 hrs by MTS assay	[PMID: 35148084]
HT-22	IC₅₀	1 μM Compound: 48	Cytotoxicity against mouse HT-22 cells assessed as reduction in cell viability incubated for 48 hrs by MTS assay Cytotoxicity against mouse HT-22 cells assessed as reduction in cell viability incubated for 48 hrs by MTS assay	[PMID: 36876904]
K562	GI₅₀	>20 μM Compound: 1, PKC412	Inhibition of wild type BCR/ABL in FLT3 deficient human K562 cells assessed as cell growth inhibition after 72 hrs by MTS assay Inhibition of wild type BCR/ABL in FLT3 deficient human K562 cells assessed as cell growth inhibition after 72 hrs by MTS assay	[PMID: 26081023]
K562	IC₅₀	>10 μM Compound: PKC-412	Antiproliferative activity against human K562 cells measured after 72 hrs by Celltiter-Glo assay Antiproliferative activity against human K562 cells measured after 72 hrs by Celltiter-Glo assay	[PMID: 31361136]
K562	GI₅₀	>20000 nM Compound: 4; PKC412	Antiproliferative activity against human K562 expressing wild type BCR/ABL assessed as cell growth inhibition after 72 hrs by CellTiter 96 AQueous One Solution Cell Proliferation assay Antiproliferative activity against human K562 expressing wild type BCR/ABL assessed as cell growth inhibition after 72 hrs by CellTiter 96 AQueous One Solution Cell Proliferation assay	[PMID: 31721578]
Kasumi 1	GI₅₀	284 nM Compound: 4; PKC412	Antiproliferative activity against human Kasumi-1 harboring c-kit N822K mutant assessed as cell growth inhibition after 72 hrs by CellTiter 96 AQueous One Solution Cell Proliferation assay Antiproliferative activity against human Kasumi-1 harboring c-kit N822K mutant assessed as cell growth inhibition after 72 hrs by CellTiter 96 AQueous One Solution Cell Proliferation assay	[PMID: 31721578]
L02	IC₅₀	8.1 μM Compound: PKC-412	Cytotoxicity against human L02 cells assessed as cell growth inhibition incubated for 72 hrs by Cell Titer-Glo assay Cytotoxicity against human L02 cells assessed as cell growth inhibition incubated for 72 hrs by Cell Titer-Glo assay	[PMID: 37857311]
MOLM-13	GI₅₀	0.055 μM Compound: 1, PKC412	Inhibition of FLT3 ITD heterozygous mutant in human MOLM-13 cells assessed as cell growth inhibition after 72 hrs by MTS assay Inhibition of FLT3 ITD heterozygous mutant in human MOLM-13 cells assessed as cell growth inhibition after 72 hrs by MTS assay	[PMID: 26081023]
MOLM-13	IC₅₀	0.0047 μM Compound: PKC412	Cytotoxicity against human MOLM13 cells after 72 hrs by MTS assay Cytotoxicity against human MOLM13 cells after 72 hrs by MTS assay	[PMID: 29350920]
MOLM-13	GI₅₀	55 nM Compound: 4; PKC412	Antiproliferative activity against human MOLM13 harboring FLT3-ITD mutant assessed as cell growth inhibition after 72 hrs by CellTiter 96 AQueous One Solution Cell Proliferation assay Antiproliferative activity against human MOLM13 harboring FLT3-ITD mutant assessed as cell growth inhibition after 72 hrs by CellTiter 96 AQueous One Solution Cell Proliferation assay	[PMID: 31721578]
MOLM-13	IC₅₀	262.9 nM Compound: Midostaurin	Antiproliferative activity against Sunitinib-resistant human MOLM-13 cells incubated for 48 hrs by CCK8 assay Antiproliferative activity against Sunitinib-resistant human MOLM-13 cells incubated for 48 hrs by CCK8 assay	[PMID: 38655686]
MOLM-13	IC₅₀	677 nM Compound: Midostaurin	Antiproliferative activity against Quizartinib-resistant human MOLM-13 cells incubated for 48 hrs by CCK8 assay Antiproliferative activity against Quizartinib-resistant human MOLM-13 cells incubated for 48 hrs by CCK8 assay	[PMID: 38655686]
MV4-11	IC₅₀	12 nM Compound: PKC-412	Cytotoxicity against human MV4-11 cells after 72 hrs by cell titer-blue assay Cytotoxicity against human MV4-11 cells after 72 hrs by cell titer-blue assay	[PMID: 19654408]
MV4-11	GI₅₀	0.038 μM Compound: 1, PKC412	Inhibition of FLT3 ITD homozygous mutant in human MV4-11 cells assessed as cell growth inhibition after 72 hrs by MTS assay Inhibition of FLT3 ITD homozygous mutant in human MV4-11 cells assessed as cell growth inhibition after 72 hrs by MTS assay	[PMID: 26081023]
MV4-11	IC₅₀	0.04 μM Compound: PKC-412	Antiproliferative activity against human MV4-11 cells measured after 72 hrs by Celltiter-Glo assay Antiproliferative activity against human MV4-11 cells measured after 72 hrs by Celltiter-Glo assay	[PMID: 31361136]
MV4-11	GI₅₀	38 nM Compound: 4; PKC412	Antiproliferative activity against human MV4-11 harboring FLT3-ITD mutant assessed as cell growth inhibition after 72 hrs by CellTiter 96 AQueous One Solution Cell Proliferation assay Antiproliferative activity against human MV4-11 harboring FLT3-ITD mutant assessed as cell growth inhibition after 72 hrs by CellTiter 96 AQueous One Solution Cell Proliferation assay	[PMID: 31721578]
MV4-11	IC₅₀	0.02 μM Compound: PKC-412	Cytotoxicity against human MV4-11 cells assessed as cell growth inhibition incubated for 72 hrs by Cell Titer-Glo assay Cytotoxicity against human MV4-11 cells assessed as cell growth inhibition incubated for 72 hrs by Cell Titer-Glo assay	[PMID: 37857311]
OCI-AML2	GI₅₀	6244 μM Compound: PKC412	Antiproliferative activity against patient derived OCI-AML2 cells harboring wild type FLT3 assessed as inhibition of cell growth incubated for 72 hrs by CCK-8 assay Antiproliferative activity against patient derived OCI-AML2 cells harboring wild type FLT3 assessed as inhibition of cell growth incubated for 72 hrs by CCK-8 assay	[PMID: 30565931]
PBMC	IC₅₀	>10 μM Compound: PKC-412	Cytotoxicity against human PBMC cells measured after 72 hrs by Celltiter-Glo assay Cytotoxicity against human PBMC cells measured after 72 hrs by Celltiter-Glo assay	[PMID: 31361136]
RS4-11	IC₅₀	13 nM Compound: PKC-412	Inhibition of FLT3 ITD mutant autophosphorylation in human RS4-11 cells after 2 hrs by electrochemiluminescence assay Inhibition of FLT3 ITD mutant autophosphorylation in human RS4-11 cells after 2 hrs by electrochemiluminescence assay	[PMID: 19654408]
RS4-11	IC₅₀	15 nM Compound: PKC-412	Inhibition of FLT3 autophosphorylation in human RS4-11 cells after 2 hrs by electrochemiluminescence assay Inhibition of FLT3 autophosphorylation in human RS4-11 cells after 2 hrs by electrochemiluminescence assay	[PMID: 19654408]
RS4-11	GI₅₀	400 nM Compound: 4; PKC412	Antiproliferative activity against human RS4:11 expressing native FLT3 assessed as cell growth inhibition after 72 hrs by CellTiter 96 AQueous One Solution Cell Proliferation assay Antiproliferative activity against human RS4:11 expressing native FLT3 assessed as cell growth inhibition after 72 hrs by CellTiter 96 AQueous One Solution Cell Proliferation assay	[PMID: 31721578]
Sf9	IC₅₀	0.037 μM Compound: 1, PKC412	Inhibition of wild type GST-tagged FLT3 kinase domain (Y567 to S993) (unknown origin) expressed in baculovirus infected insect Sf9 cells using Her2 peptide as substrate after 4 hrs by Kinase-Glo assay Inhibition of wild type GST-tagged FLT3 kinase domain (Y567 to S993) (unknown origin) expressed in baculovirus infected insect Sf9 cells using Her2 peptide as substrate after 4 hrs by Kinase-Glo assay	[PMID: 26081023]
Sf9	IC₅₀	0.08 μM Compound: 1, PKC412	Inhibition of recombinant GST-tagged Aurora-A kinase domain (S123 to S401) (unknown origin) expressed in insect Sf9 cells using tetra(LRRASLG) peptide as substrate after 90 mins by Kinase-Glo assay Inhibition of recombinant GST-tagged Aurora-A kinase domain (S123 to S401) (unknown origin) expressed in insect Sf9 cells using tetra(LRRASLG) peptide as substrate after 90 mins by Kinase-Glo assay	[PMID: 26081023]
Sf9	IC₅₀	0.25 μM Compound: 1, PKC412	Inhibition of recombinant GST-tagged VEGFR2 kinase domain (V789 to V1356) (unknown origin) expressed in insect Sf9 cells using polyGlu4:Tyr peptide as substrate after 120 mins by Kinase-Glo assay Inhibition of recombinant GST-tagged VEGFR2 kinase domain (V789 to V1356) (unknown origin) expressed in insect Sf9 cells using polyGlu4:Tyr peptide as substrate after 120 mins by Kinase-Glo assay	[PMID: 26081023]
Sf9	IC₅₀	109 nM Compound: 4; PKC412	Inhibition of recombinant N-terminal 6x-His-tagged c-KIT (547 to 935 residues)/(694 to 753 residues deletion) (unknown origin) expressed in baculovirus infected Sf9 insect cells using poly (Glu,Tyr) 4:1 as substrate measured after 150 mins in presence of Inhibition of recombinant N-terminal 6x-His-tagged c-KIT (547 to 935 residues)/(694 to 753 residues deletion) (unknown origin) expressed in baculovirus infected Sf9 insect cells using poly (Glu,Tyr) 4:1 as substrate measured after 150 mins in presence of	[PMID: 31721578]
Sf9	IC₅₀	40 nM Compound: 4; PKC412	Inhibition of wild type recombinant GST-tagged FLT3 (Y567 to S993 residues) (unknown origin) expressed in baculovirus infected Sf9 insect cells using Her2 peptide as substrate measured after 4 hrs in presence of ATP by Kinase-Glo Plus reagent-based lumine Inhibition of wild type recombinant GST-tagged FLT3 (Y567 to S993 residues) (unknown origin) expressed in baculovirus infected Sf9 insect cells using Her2 peptide as substrate measured after 4 hrs in presence of ATP by Kinase-Glo Plus reagent-based lumine	[PMID: 31721578]
T-24	IC₅₀	0.029 μM Compound: 35	Antiproliferative activity against human T-24 cells assessed as inhibition of growth inhibition Antiproliferative activity against human T-24 cells assessed as inhibition of growth inhibition	[PMID: 36155354]
U-937	GI₅₀	1.4 μM Compound: 1, PKC412	Cytotoxicity against FLT3-deficient human U937 cells assessed as cell growth inhibition after 72 hrs by MTS assay Cytotoxicity against FLT3-deficient human U937 cells assessed as cell growth inhibition after 72 hrs by MTS assay	[PMID: 26081023]
U-937	GI₅₀	1400 nM Compound: 4; PKC412	Antiproliferative activity against human U937 assessed as cell growth inhibition after 72 hrs by CellTiter 96 AQueous One Solution Cell Proliferation assay Antiproliferative activity against human U937 assessed as cell growth inhibition after 72 hrs by CellTiter 96 AQueous One Solution Cell Proliferation assay	[PMID: 31721578]

In Vitro

Midostaurin (PKC412) shows a broad antiproliferative activity against various tumor and normal cell lines in vitro, and is able to reverse the Pgp-mediated multidrug resistance of tumor cells in vitro. Exposure of cells to Midostaurin (PKC412) results in a dose-dependent increase in the G2/M phase of the cell cycle concomitant with increased polyploidy, apoptosis and enhanced sensitivity to ionizing radiation^[1].
Midostaurin (PKC412) induces substantial inhibition of KIT-, Lyn-, and STAT5 activity, but does not suppress Btk in HMC-1 cells and primary neoplastic mast cells^[3].
Midostaurin (PKC412) inhibits EN fusion tyrosine kinase in hematopoietic Ba/F3 cells. Midostaurin (PKC412) significantly inhibits EN phosphorylation in M0-91 and IMS-M2 cells in a dose-dependent manner^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

Midostaurin (PKC412) strongly inhibits retinal neovascularization as well as laser-induced choroidal neovascularization in murine models^[1].
Midostaurin (PKC412) (25 mg/kg, i.p.) protects mouse livers of the K18 Arg90Cys-overexpressing transgenic mice from Fas-induced apoptosis^[5].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Clinical Trial

NCT Number	Sponsor	Condition	Start Date	Phase A549
NCT01329991	Plexxikon\|		2011-05	PHASE1

Chemical Information

CAS. Nr. 120685-11-2
Appearance Solid
Molecular Weight 570.64
Formel C₃₅H₃₀N₄O₄
Color White to yellow
SMILES

O=C(C1=CC=CC=C1)N(C)[C@H]2[C@@H](OC)[C@@]3(C)N(C4=C5C=CC=C4)C6=C5C7=C(C(NC7)=O)C8=C6N(C9=CC=CC=C98)[C@@](O3)([H])C2
Synonyms

PKC412; CGP 41251
Versand

Room temperature in continental US; may vary elsewhere.
Speicherung

-20°C, sealed storage, away from moisture

* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

Publications (39)

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Cell

Small Molecules Co-targeting CKIα and the Transcriptional Kinases CDK7/9 Control AML in Preclinical Models. [Abstract]

2018 Sep 20;175(1):171-185.e25. PMID: 30146162

Midostaurin purchased from MedChemExpress. Usage Cited in: Cell. 2018 Sep 20;175(1):171-185.e25. [Abstract]

Tet2^−/−;Flt3 ^ITD AML mouse data. (A) WBC counts in PB from A51-, midostaurin (Mido)-, or vehicle (Veh)-treated Tet2−/−; Flt3 ITD AML mice at the day of sacrifice; (B) Spleen images of representative three mice from each group. C57BL/6 WT mice were irradiated with sub-lethal (500 rad) irradiation and one day later mice were injected (via tail vein) with 5 × 10⁵ spleen cells isolated from 4th generation Tet2^−/−;Flt3 ^ITD mice. Seven days post leukemia inoculation, mice were orally (gavage) treated with either A51 (Di-HCL salt) (5mg/kg), midostaurin (35mg/kg) or vehicle for 18 days (6 days a week) and were sacrificed 9 days after stopping the treatment.

Midostaurin purchased from MedChemExpress. Usage Cited in: Cell. 2018 Sep 20;175(1):171-185.e25. [Abstract]

Tet2^−/−;Flt3 ^ITD AML mouse data. Representative H&E images of BM and spleen from the same mice. C57BL/6 WT mice were irradiated with sub-lethal (500 rad) irradiation and one day later mice were injected (via tail vein) with 5 × 10⁵ spleen cells isolated from 4th generation Tet2^−/−;Flt3 ^ITD mice. Seven days post leukemia inoculation, mice were orally (gavage) treated with either A51 (Di-HCL salt) (5mg/kg), midostaurin (35mg/kg) or vehicle for 18 days (6 days a week) and were sacrificed 9 days after stopping the treatment.

Midostaurin purchased from MedChemExpress. Usage Cited in: Cell. 2018 Sep 20;175(1):171-185.e25. [Abstract]

WB analysis of AML cells from mouse spleen of Tet2^−/−;Flt3 ^ITD AML mice treated ex vivo with A-series inhibitors A51, A86, A64, and midostaurin (125, 250, 500 nM) at the indicated concentrations or with DMSO (–) for 5 hr. PP2Ac, loading control.
Blood

TARGETING FLT3 BY NEW-GENERATION ANTIBODY-DRUG-CONJUGATE IN COMBINATION WITH KINASE INHIBITORS FOR TREATMENT OF AML. [Abstract]

2023 Mar 2;141(9):1023-1035. PMID: 35981498
Nat Commun

NCF4 attenuates colorectal cancer progression by modulating inflammasome activation and immune surveillance. [Abstract]

2024 Jun 17;15(1):5170. PMID: 38886341

Midostaurin purchased from MedChemExpress. Usage Cited in: Nat Commun. 2024 Jun 17;15(1):5170. [Abstract]

WT and Ncf4^–/– BMDMs were pretreated with Midostaurin (PKC412; 25 nm, 50 nm, and 100 nm) for 1 h, and further stimulated with LPS (500 ng/mL, 4 h) plus ATP (5 mM, 60 min) for NLRP3 inflammasome activation. Immunoblot analysis of pro-caspase-1 (Pro-Casp1) and its subunit p20 in PKC412-treated and untreated BMDMs with and without treatment for NLRP3 inflammasome activation.

Midostaurin purchased from MedChemExpress. Usage Cited in: Nat Commun. 2024 Jun 17;15(1):5170. [Abstract]

WT and Ncf4^-/- BMDMs were pretreated with Midostaurin (PKC412; 25 nm, 50 nm, and 100 nm) for 1 h, and further stimulated with LPS (500 ng/mL, 4 h) plus ATP (5 mM, 60 min) for NLRP3 inflammasome activation. Analysis of IL-1β release in PKC412-treated and untreated BMDMs with and without treatment for NLRP3 inflammasome activation.
Nat Commun

Signature-driven repurposing of Midostaurin for combination with MEK1/2 and KRASG12C inhibitors in lung cancer. [Abstract]

2023 Oct 10;14(1):6332. PMID: 37816716
Sci Transl Med

PP2A inhibition is a druggable MEK inhibitor resistance mechanism in KRAS-mutant lung cancer cells. [Abstract]

2018 Jul 18;10(450):eaaq1093. PMID: 30021885
Adv Sci (Weinh)

Inhibition of Calcium-Dependent Lipid Droplets Relocation of ACSL4-PKCβ-ALOX15 Complex Alleviates Ferroptosis and Acute Pancreatitis. [Abstract]

2026 Apr;13(19):e15768. PMID: 41589658
Biomaterials

Automated discovery of nanomaterials via drug aggregation induced emission. [Abstract]

2022 Oct:289:121800. PMID: 36166893
Cancer Lett

High-content drug screening in zebrafish xenografts reveals high efficacy of dual MCL-1/BCL-XL inhibition against Ewing sarcoma. [Abstract]

2023 Feb 1:554:216028. PMID: 36462556
Cancer Lett

All-trans retinoic acid exerts selective anti-FLT3-ITD acute myeloid leukemia efficacy through downregulating Chk1 kinase. [Abstract]

2020 Mar 31;473:130-138. PMID: 31904486
Acta Biomater

Lipopolymer/siRNA complexes engineered for optimal molecular and functional response with chemotherapy in FLT3-mutated acute myeloid leukemia. [Abstract]

2024 Sep 3:S1742-7061(24)00505-1. PMID: 39236794
Haematologica

MDM2- and FLT3-inhibitors in the treatment of FLT3-ITD acute myeloid leukemia, specificity and efficacy of NVP-HDM201 and midostaurin. [Abstract]

2018 Nov;103(11):1862-1872. PMID: 29976747

Midostaurin purchased from MedChemExpress. Usage Cited in: Haematologica. 2018 Nov;103(11):1862-1872. [Abstract]

Induction of tumor suppressor protein p53 in MV4-11 (A) and MOLM-13 cells (B) treated for 24 hours with the indicated amounts of NVP-HDM201 and midostaurin. Relative quantitation of CDKN1A mRNA (C) and MCL-1 mRNA (D) in AML cells treated for 24 hours with PKC412 and NVP-HDM201 alone or in combination.
Mol Syst Biol

Illuminating phenotypic drug responses of sarcoma cells to kinase inhibitors by phosphoproteomics. [Abstract]

2024 Jan;20(1):28-55. PMID: 38177929
Biomed Pharmacother

Jaceosidin, a natural polymethoxyflavone, suppresses leukemia cell growth and impairs lipid metabolism-dependent survival in AML and cytarabine-resistant cells. [Abstract]

2025 Oct 19:192:118654. PMID: 41115391
J Transl Med

Single-cell profiling of SLC family transporters: uncovering the role of SLC7A1 in osteosarcoma. [Abstract]

2025 Jan 22;23(1):103. PMID: 39844299
Arch Toxicol

Selective inhibition of aldo-keto reductase 1C3: a novel mechanism involved in midostaurin and daunorubicin synergism. [Abstract]

2021 Jan;95(1):67-78. PMID: 33025066
J Med Chem

Comparative Efficacy and Selectivity of Pharmacological Inhibitors of DYRK and CLK Protein Kinases. [Abstract]

2023 Mar 23;66(6):4106-4130. PMID: 36876904
Sci Signal

Blockade of ROS production inhibits oncogenic signaling in acute myeloid leukemia and amplifies response to precision therapies. [Abstract]

2023 Mar 28;16(778):eabp9586. PMID: 36976863
Int J Mol Sci

An Autocrine Regulator Loop Involving Tumor Necrosis Factor and Chemokine (C-C motif) Ligand-2 Is Activated by Transforming Growth Factor-β in Rat Basophilic Leukemia-2H3 Mast Cells. [Abstract]

2025 Apr 30;26(9):4263. PMID: 40362499
Int J Mol Sci

A Functional Pipeline of Genome-Wide Association Data Leads to Midostaurin as a Repurposed Drug for Alzheimer's Disease. [Abstract]

2023 Jul 28;24(15):12079. PMID: 37569459
Eur J Pharmacol

Quizartinib-induced resistance drives clonal emergence of MV4-11 cells with molecular alterations enabling multidrug antileukemic escape. [Abstract]

2026 May 10:1023:178877. PMID: 41997407
Eur J Pharmacol

The immune thrombocytopenia therapeutic Avatrombopag alleviates osteoporosis by targeting NFATc1 signaling. [Abstract]

2026 Jan 10:1010:178377. PMID: 41297758
Cancers (Basel)

BMI1-Inhibitor PTC596 in Combination with MCL1 Inhibitor S63845 or MEK Inhibitor Trametinib in the Treatment of Acute Leukemia. [Abstract]

2021 Feb 2;13(3):581. PMID: 33540760
Cancers

Cotargeting of XPO1 Enhances the Antileukemic Activity of Midostaurin and Gilteritinib in Acute Myeloid Leukemia. [Abstract]

2020 Jun 14;12(6):1574. PMID: 32545904
J Cell Mol Med

Inactivation of CDK12 Enhances Mitochondrial Efficiency to Suppress DNA Damage. [Abstract]

2026 Apr;30(7):e71101. PMID: 41896195
J Cell Mol Med

Effects of the multi-kinase inhibitor midostaurin in combination with chemotherapy in models of acute myeloid leukaemia. [Abstract]

2020 Mar;24(5):2968-2980. PMID: 31967735
J Cell Mol Med

The combination of FLT3 and SYK kinase inhibitors is toxic to leukaemia cells with CBL mutations. [Abstract]

2020 Feb;24(3):2145-2156. PMID: 31943762

Midostaurin purchased from MedChemExpress. Usage Cited in: J Cell Mol Med. 2020 Feb;24(3):2145-2156. [Abstract]

Effects of Midostaurin in vivo against mice harbouring Ba/F3.FLT3(wt).CBL.Y371H-luc+ cells. Supine and Prone (High Scale), Days 12-19. Representative Images (n = 5).
Sci Rep

MEK inhibition enhances the response to tyrosine kinase inhibitors in acute myeloid leukemia. [Abstract]

2019 Dec 9;9(1):18630. PMID: 31819100
Br J Haematol

Comparison of effects of midostaurin, crenolanib, quizartinib, gilteritinib, sorafenib and BLU-285 on oncogenic mutants of KIT, CBL and FLT3 in haematological malignancies. [Abstract]

2019 Nov;187(4):488-501. PMID: 31309543
SLAS Discov

A Multiplexed Screening Assay to Evaluate Chemotherapy-Induced Myelosuppression Using Healthy Peripheral Blood and Bone Marrow. [Abstract]

2018 Aug;23(7):687-696. PMID: 29865911
PLoS One

A novel small molecule screening assay using normal human chondrocytes toward osteoarthritis drug discovery. [Abstract]

2024 Nov 1;19(11):e0308647. PMID: 39485774
Res Sq

2026 Jun 15.
bioRxiv

2025 Sep 21.
bioRxiv

Cheminformatic identification of small molecules targeting acute myeloid leukemia. [Abstract]

2025 May 24:2025.05.20.655224. PMID: 40475511
SSRN

2025 Feb 13.
University of Colorado Denver

2024.
Patent

US20230146387A1.
Patent

US20220249529A1.
Patent

US20200323850A1.
Charles University

2020 Jul.

Lösungsmittel & Löslichkeit

In Vitro:

DMSO : 50 mg/mL (87.62 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

1.7524 mL

8.7621 mL

17.5242 mL

5 mM

0.3505 mL

1.7524 mL

3.5048 mL

10 mM

0.1752 mL

0.8762 mL

1.7524 mL

Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.

Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Molaritätsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 50% PEG400 50% Saline

Solubility: 5 mg/mL (8.76 mM); Suspended solution; Need ultrasonic

Protocol 2

Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline

Solubility: ≥ 2.5 mg/mL (4.38 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 2.5 mg/mL (4.38 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

Working Solution

For the following dissolution methods, please prepare the working solution directly:

It is recommended to prepare fresh solutions and use them promptly within a short period of time.

The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 1% CMC/0.5% Tween-80 in Saline water

Solubility: 5 mg/mL (8.76 mM); Suspended solution; Need ultrasonic

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
Saline +

The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).

Working solution concentration: 0.22 mg/mL

Protokoll

Cell Assay^[3]

Proliferation is determined by trypan blue dye exclusion test. Cells in suspension are seeded in six-well plates at a density of 1×10⁵ cells/mL in the presence of different concentrations of PKC412 for 3 days. In control wells, DMSO instead of Midostaurin (PKC412) is added. After the treatment, 10 μL of the cell suspension is mixed with 10 μL of 0.4% trypan blue, and alive cells are counted manually using a hemacytometer. Results are calculated as the percentage of the values measured when cells are grown in the absence of the reagent. All experiments are performed in triplicate^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration^[4]

K8-deficient, K18-deficient, and human K18 R90C-overexpressing mice with age of 6-8 weeks are used in the assay. Age and sex matched mice are treated with Midostaurin (25 mg/kg), daily for 4 d or with an equal volume of DMSO as vehicle (both administered intraperitoneally). On day 5 post-treatment, apoptosis is induced by intraperitoneal injection of Fas ligand (Fas-L) (0.15 μg/g body weight). Mice are fasted overnight before Fas Ab injection, and 18 mice are used per DMSO or Midostaurin (PKC412) group for the Fas-treated mice while 6 mice are used per DMSO or Midostaurin (PKC412) group for the control non-Fas-treated mice. Mice are sacrificed by CO₂ inhalation 6 h after Fas Ab injection. Blood is collected by intracardiac puncture, and livers are harvested for hematoxylin and eosin (HE) staining (after fixation in 10% formalin) or frozen in optimum cutting temperature compound for immunofluorescence staining^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (290 KB)
SDS (394 KB)
- English - EN (394 KB)
- Français - FR (394 KB)
- Deutsch - DE (394 KB)
- Norwegian - NO (394 KB)
- Español - ES (394 KB)
- Swedish - SV (394 KB)
- Italian - IT (394 KB)
- Korean - KR (394 KB)
- Portuguese - PT (394 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

Verweise

[1]. Fabbro D, et al. PKC412--a protein kinase inhibitor with a broad therapeutic potential. Anticancer Drug Des. 2000 Feb;15(1):17-28. [Content Brief]

[2]. Fabbro D, et al. Inhibitors of protein kinases: CGP 41251, a protein kinase inhibitor with potential as an anticancer agent. Pharmacol Ther. 1999 May-Jun;82(2-3):293-301. [Content Brief]

[3]. Huige Li, et al. Midostaurin upregulates eNOS gene expression and preserves eNOS function in the microcirculation of the mouse. Nitric Oxide. 2005 Jun;12(4):231-6. [Content Brief]

[4]. Gleixner KV, et al. Synergistic growth-inhibitory effects of Midostaurin (PKC412) on neoplastic mast cells carrying KIT D816V. Haematologica. 2013 Sep;98(9):1450-7. [Content Brief]

[5]. Chi HT, et al. ETV6-NTRK3 as a therapeutic target of small molecule inhibitor PKC412. Biochem Biophys Res Commun. 2012 Dec 7;429(1-2):87-92. [Content Brief]

[6]. Kwan R, et al. PKC412 normalizes mutation-related keratin filament disruption and hepatic injury in mice by promoting keratin-myosin binding. Hepatology. 2015 Dec;62(6):1858-69. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
DMSO	1 mM	1.7524 mL	8.7621 mL	17.5242 mL	43.8105 mL
	5 mM	0.3505 mL	1.7524 mL	3.5048 mL	8.7621 mL
	10 mM	0.1752 mL	0.8762 mL	1.7524 mL	4.3810 mL
	15 mM	0.1168 mL	0.5841 mL	1.1683 mL	2.9207 mL
	20 mM	0.0876 mL	0.4381 mL	0.8762 mL	2.1905 mL
	25 mM	0.0701 mL	0.3505 mL	0.7010 mL	1.7524 mL
	30 mM	0.0584 mL	0.2921 mL	0.5841 mL	1.4603 mL
	40 mM	0.0438 mL	0.2191 mL	0.4381 mL	1.0953 mL
	50 mM	0.0350 mL	0.1752 mL	0.3505 mL	0.8762 mL
	60 mM	0.0292 mL	0.1460 mL	0.2921 mL	0.7302 mL
	80 mM	0.0219 mL	0.1095 mL	0.2191 mL	0.5476 mL

Keywords

Midostaurin

39 Cited Publications

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Midostaurin

Apoptosis Compound Library

Epigenetics Compound Library

Immunology/Inflammation Compound Library

Kinase Inhibitor Library

Protein Tyrosine Kinase Compound Library

TGF-beta/Smad Compound Library

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Publications Citing Use of MedChemExpress (MCE) Midostaurin

Alle PKC Isoform-spezifische Produkte anzeigen

Alle VEGFR Isoform-spezifische Produkte anzeigen

Alle NO Synthase Isoform-spezifische Produkte anzeigen

Biologische Aktivität

Chemical Information

Publications (39)

Lösungsmittel & Löslichkeit

Protokoll

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

Midostaurin Related Classifications

HY-10230 Related Classifications