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Compound Detail

CHEMBL608533

MIDOSTAURIN
💊 Approved Drug
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💊 Approved Drug
CO[C@@H]1[C@H](N(C)C(=O)c2ccccc2)C[C@H]2O[C@]1(C)n1c3ccccc3c3c4c(c5c6ccccc6n2c5c31)C(=O)NC4
ChEMBL ↗ Properties Compare Identifier

Basic Information

ChEMBL ID CHEMBL608533
Name MIDOSTAURIN
Phase Approved
Structure Type MOL
InChI Key BMGQWWVMWDBQGC-IIFHNQTCSA-N
Therapeutic ✓ Yes

Known Names

CGP 41251 CGP-41251 Midostaurin Midostaurina Midostaurine N-benzoylstaurosporine NSC-656576 NVP-PKC412 PKC 412 Pkc-412 Rydapt
871
Targets
1,387
Activities
3
Assay Types
8
PK Parameters
20
Publications
11
Known Names
10
Indications
5
Mechanisms

Molecular Properties

570.6
MW (Da)
5.91
ALogP
6
HBA
1
HBD
77.7
PSA (Ų)
0.29
QED
2
Ro5 Violations
3
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2017
Availability Prescription
Chirality Single Enantiomer

Routes of Administration

Oral

Flags

Natural Product First in Class
USAN Year 2004

Extended Properties

Molecular Formula C35H30N4O4
MW 570.65
Aromatic Rings 6
Heavy Atoms 43
NP-Likeness 0.66

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Tyrosine-protein kinase receptor FLT3 inhibitor INHIBITOR Receptor-type tyrosine-protein kinase FLT3 ✓ ✓
Stem cell growth factor receptor inhibitor INHIBITOR Mast/stem cell growth factor receptor Kit ✓ ✓
Platelet-derived growth factor receptor inhibitor INHIBITOR Platelet-derived growth factor receptor ✓ ✓
Protein kinase C (PKC) inhibitor INHIBITOR Protein kinase C (PKC) ✓ ✓
Vascular endothelial growth factor receptor 2 inhibitor INHIBITOR Vascular endothelial growth factor receptor 2 ✓ ✓

Indications

Leukemia, Mast-Cell Leukemia, Myeloid, Acute Mastocytosis Mastocytosis, Systemic Neoplasms Leukemia Myelodysplastic Syndromes Liver Diseases Precursor Cell Lymphoblastic Leukemia-Lymphoma Rectal Neoplasms

ATC Classification

L01EX10
midostaurin
Level 1: ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
Level 2: ANTINEOPLASTIC AGENTS

Activity Summary

IC50 728 meas. best 9.0
Kd 658 meas. best 8.7
EC50 1 meas. best 6.38

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Receptor-type tyrosine-protein kinase FLT3
CHEMBL1974
 IC50 9.0 7.28 1.0 10
Receptor-type tyrosine-protein kinase FLT3
CHEMBL1974
 Kd 8.7 8.0079 2.0 24
BaF3
CHEMBL614524
 IC50 8.7 7.7388 2.0 8
EOL1
CHEMBL614489
 IC50 8.42 7.85 3.8 2
MOLM-13
CHEMBL3706572
 IC50 8.33 7.0267 4.7 3
Mast/stem cell growth factor receptor Kit
CHEMBL1936
 Kd 8.11 6.9995 7.7 21
Epidermal growth factor receptor
CHEMBL203
 Kd 8.06 5.9589 8.8 28
Serine/threonine-protein kinase N1
CHEMBL3384
 Kd 8.03 7.7025 9.3 4
Serine/threonine-protein kinase TBK1
CHEMBL5408
 Kd 8.03 7.5967 9.3 3
Unchecked
CHEMBL612545
 IC50 8.0 7.12 10.0 5
Unchecked
CHEMBL612545
 Kd 7.96 6.0114 11.0 7
Tyrosine-protein kinase JAK3
CHEMBL2148
 Kd 7.92 7.92 12.0 3
MV4-11
CHEMBL613835
 IC50 7.92 7.68 12.0 4
Mitogen-activated protein kinase kinase kinase 9
CHEMBL2872
 Kd 7.82 7.82 15.0 3
Serine/threonine-protein kinase N2
CHEMBL3032
 Kd 7.82 7.82 15.0 3
Mitogen-activated protein kinase kinase kinase 19
CHEMBL6191
 Kd 7.82 7.82 15.0 2
Mitogen-activated protein kinase kinase kinase 11
CHEMBL2708
 Kd 7.77 7.102 17.0 5
Serine/threonine-protein kinase 4
CHEMBL4598
 Kd 7.77 7.5233 17.0 3
Aurora kinase A
CHEMBL4722
 Kd 7.71 6.958 19.3 5
Proto-oncogene tyrosine-protein kinase receptor Ret
CHEMBL2041
 Kd 7.7 6.8445 20.0 11
Calcium/calmodulin-dependent protein kinase type II subunit alpha
CHEMBL4147
 Kd 7.7 7.7 20.0 3
MAP/microtubule affinity-regulating kinase 3
CHEMBL5600
 Kd 7.68 7.25 21.0 4
T-24
CHEMBL614774
 IC50 7.54 6.63 29.0 2
Mast/stem cell growth factor receptor Kit
CHEMBL1936
 IC50 7.52 7.24 30.0 2
Calcium/calmodulin-dependent protein kinase type II subunit delta
CHEMBL2801
 Kd 7.44 7.1375 36.0 4
eIF-2-alpha kinase GCN2
CHEMBL5358
 Kd 7.41 7.41 39.0 3
NKM-1
CHEMBL2366133
 IC50 7.4 7.4 39.4 1
Serine/threonine-protein kinase 3
CHEMBL4708
 Kd 7.4 6.9067 40.0 3
NUAK family SNF1-like kinase 1
CHEMBL5784
 Kd 7.39 7.39 41.0 3
SRSF protein kinase 1
CHEMBL4375
 Kd 7.38 7.38 42.0 3
CGTH-W-1
CHEMBL2366300
 IC50 7.37 7.37 42.6 1
SW982
CHEMBL2366238
 IC50 7.34 7.34 45.6 1
Rhodopsin kinase GRK7
CHEMBL1075133
 Kd 7.32 7.32 48.0 2
AP2-associated protein kinase 1
CHEMBL3830
 Kd 7.32 7.132 48.0 5
Serine/threonine-protein kinase PRP4 homolog
CHEMBL1908382
 Kd 7.26 7.26 55.0 2
Kasumi 1
CHEMBL613988
 IC50 7.22 7.22 60.2 1
Aurora kinase B
CHEMBL2185
 Kd 7.21 6.8125 62.0 4
NCI-H1755
CHEMBL1075524
 IC50 7.2 7.2 62.7 1
NUAK family SNF1-like kinase 2
CHEMBL5698
 Kd 7.2 7.2 63.0 3
Serine/threonine-protein kinase PLK4
CHEMBL3788
 Kd 7.18 7.0525 66.0 4
ATP-dependent translocase ABCB1
CHEMBL4302
 IC50 7.17 7.17 68.0 1
Calcium/calmodulin-dependent protein kinase kinase 2
CHEMBL5284
 Kd 7.14 6.715 73.0 4
cGMP-dependent protein kinase 2
CHEMBL2896
 Kd 7.13 7.13 74.0 3
MES-SA
CHEMBL614343
 IC50 7.12 7.12 75.4 1
Aurora kinase A
CHEMBL4722
 IC50 7.1 7.1 80.0 1
SRSF protein kinase 3
CHEMBL5415
 Kd 7.1 7.1 80.0 2
Non-receptor tyrosine-protein kinase TNK1
CHEMBL5334
 Kd 7.08 6.825 83.0 4
HCC1395
CHEMBL1075454
 IC50 7.07 7.07 84.3 1
Rhodopsin kinase GRK1
CHEMBL5607
 Kd 7.07 7.07 85.0 2
CHP-212
CHEMBL1075423
 IC50 7.06 7.06 87.7 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 1426.62 ng.hr.mL-1 Mus musculus
AUC 506.4 - Chlorocebus sabaeus
Cmax 770.0 nM Mus musculus
Cmax 2812.58 nM Homo sapiens
T1/2 20.0 hr Homo sapiens
T1/2 21.0 hr Homo sapiens
Tmax 0.67 hr Mus musculus
Vd 95.2 l Homo sapiens

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Receptor-type tyrosine-protein kinase FLT3 IC50 = 1.0 nM 9.0 Inhibition of FLT3 D835Y mutant (unknown origin) 32659083
Receptor-type tyrosine-protein kinase FLT3 Kd = 2.0 nM 8.7 Binding affinity to FLT3 K663Q mutant 19654408
Receptor-type tyrosine-protein kinase FLT3 Kd = 2.0 nM 8.7 Binding constant for FLT3(K663Q) kinase domain 22037378
BaF3 IC50 = 2.0 nM 8.7 Antiproliferative activity against mouse BaF3 cells harboring FLT3 ITD/D835V mut... 37163951
EOL1 IC50 = 3.8 nM 8.42 Cytotoxicity against human EOL-1 cells after 72 hrs by MTS assay 29350920
BaF3 IC50 = 4.0 nM 8.4 Antiproliferative activity against mouse BaF3 cells harboring FLT3 D835V mutant ... 37163951
BaF3 IC50 = 4.14 nM 8.38 Antiproliferative activity against mouse BaF3 FLT3-ITD cells assessed as reducti... 32659083
MOLM-13 IC50 = 4.7 nM 8.33 Cytotoxicity against human MOLM13 cells after 72 hrs by MTS assay 29350920
Receptor-type tyrosine-protein kinase FLT3 Kd = 6.0 nM 8.22 Binding affinity to FLT3 N841I mutant 19654408
Receptor-type tyrosine-protein kinase FLT3 Kd = 6.0 nM 8.22 Binding constant for FLT3(N841I) kinase domain 22037378
Receptor-type tyrosine-protein kinase FLT3 Kd = 6.0 nM 8.22 Binding constant for FLT3(N841I) kinase domain 18183025
Receptor-type tyrosine-protein kinase FLT3 Kd = 6.8 nM 8.17 Binding constant for FLT3(D835H) kinase domain 18183025
Receptor-type tyrosine-protein kinase FLT3 Kd = 6.8 nM 8.17 Binding affinity to FLT3 D835H mutant 19654408
Receptor-type tyrosine-protein kinase FLT3 Kd = 6.8 nM 8.17 Binding constant for FLT3(D835H) kinase domain 22037378
Receptor-type tyrosine-protein kinase FLT3 Kd = 6.8 nM 8.17 Binding affinity to human FLT3 D835H mutant expressed in baculovirus expression ... 30742435
BaF3 IC50 = 7.0 nM 8.15 Antiproliferative activity against mouse BaF3 cells harboring FLT3 ITD/F691L mut... 37163951
Mast/stem cell growth factor receptor Kit Kd = 7.7 nM 8.11 Binding affinity to human KIT D816V mutant incubated for 1 hr by kinase binding ... 21429632
Mast/stem cell growth factor receptor Kit Kd = 7.7 nM 8.11 Binding constant for KIT(D816V) kinase domain 22037378
Mast/stem cell growth factor receptor Kit Kd = 7.7 nM 8.11 Binding affinity to KIT D816V mutant 19654408
Mast/stem cell growth factor receptor Kit Kd = 7.7 nM 8.11 Binding constant for KIT(D816V) kinase domain 18183025

Literature References

PubMed DOI Target Context # Activities
22037378 10.1038/nbt.1990 Tyrosine-protein kinase ABL1 15
22037378 10.1038/nbt.1990 Epidermal growth factor receptor 12
18183025 10.1038/nbt1358 Epidermal growth factor receptor 10
22037378 10.1038/nbt.1990 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform 10
19654408 10.1182/blood-2009-05-222034 Tyrosine-protein kinase ABL1 9
19654408 10.1182/blood-2009-05-222034 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform 9
26254279 10.18632/oncotarget.4214 Protein kinase C (PKC) 9
22037378 10.1038/nbt.1990 Mast/stem cell growth factor receptor Kit 8
19654408 10.1182/blood-2009-05-222034 Receptor-type tyrosine-protein kinase FLT3 8
18183025 10.1038/nbt1358 Tyrosine-protein kinase ABL1 7
22037378 10.1038/nbt.1990 Receptor-type tyrosine-protein kinase FLT3 7
20156689 10.1016/j.bmc.2010.01.056 Macrophage colony-stimulating factor 1 receptor 6
37163951 10.1016/j.ejmech.2023.115448 BaF3 6
19654408 10.1182/blood-2009-05-222034 Mast/stem cell growth factor receptor Kit 6
19654408 10.1182/blood-2009-05-222034 Epidermal growth factor receptor 6
19654408 10.1182/blood-2009-05-222034 Unchecked 6
18183025 10.1038/nbt1358 Receptor-type tyrosine-protein kinase FLT3 6
30742435 10.1021/acs.jmedchem.8b01714 Receptor-type tyrosine-protein kinase FLT3 5
18183025 10.1038/nbt1358 Mast/stem cell growth factor receptor Kit 5
33069066 10.1016/j.bmc.2020.115675 Aspartyl/asparaginyl beta-hydroxylase 5

Data from ChEMBL 36 via Core Engine