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Details

Stereochemistry ABSOLUTE
Molecular Formula C35H30N4O4
Molecular Weight 570.6384
Optical Activity UNSPECIFIED
Defined Stereocenters 4 / 4
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MIDOSTAURIN

SMILES

C[C@]12[C@@]([H])([C@@]([H])(C[C@]([H])(n3c4ccccc4c5c6c(CN=C6O)c7c8ccccc8n1c7c53)O2)N(C)C(=O)c9ccccc9)OC

InChI

InChIKey=BMGQWWVMWDBQGC-IIFHNQTCSA-N
InChI=1S/C35H30N4O4/c1-35-32(42-3)25(37(2)34(41)19-11-5-4-6-12-19)17-26(43-35)38-23-15-9-7-13-20(23)28-29-22(18-36-33(29)40)27-21-14-8-10-16-24(21)39(35)31(27)30(28)38/h4-16,25-26,32H,17-18H2,1-3H3,(H,36,40)/t25-,26-,32-,35+/m1/s1

HIDE SMILES / InChI

Molecular Formula C35H30N4O4
Molecular Weight 570.6384
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 4 / 4
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment:: description was created based on several sources, including: https://www.novartis.com/news/media-releases/novartis-drug-pkc412-midostaurin-granted-fda-priority-review-newly-diagnosed | http://adisinsight.springer.com/drugs/800002524

Midostaurin, a derivate of staurosporine (N-benzoylstaurosporine), is a broad-spectrum inhibitor of Ser/Thr and Tyr protein kinases. Midostaurin showed broad antiproliferative activity against various tumor and normal cell lines in vitro and is able to reverse the p-glycoprotein-mediated multidrug resistance of tumor cells in vitro. Midostaurin showed in vivo antitumor activity as single agent and inhibited angiogenesis in vivo. At the end of 2016 FDA granted Priority Review to the PKC412 (midostaurin) new drug application (NDA) for the treatment of acute myeloid leukemia (AML) in newly-diagnosed adults with an FMS-like tyrosine kinase-3 (FLT3) mutation, as well as for the treatment of advanced systemic mastocytosis (SM).

Originator

Curator's Comment:: https://www.ncbi.nlm.nih.gov/pubmed/2714889

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
528.0 nM [IC50]
Target ID: ETV6-NTRK3
Target ID: P04409
Gene ID: 282001.0
Gene Symbol: PRKCA
Target Organism: Bos taurus (Bovine)
27.0 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
RYDAPT

Approved Use

RYDAPT is a kinase inhibitor indicated for the treatment of adult patients with: Newly diagnosed acute myeloid leukemia (AML) that is FLT3 mutation-positive as detected by an FDA-approved test, in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation

Launch Date

1.49333764E12
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Analogs of staurosporine: potential anticancer drugs?
1998 Nov
Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry.
2010 Nov 24
Midostaurin (PKC412) modulates differentiation and maturation of human myeloid dendritic cells.
2010 Sep
Discovery of 3-(2,6-dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea (NVP-BGJ398), a potent and selective inhibitor of the fibroblast growth factor receptor family of receptor tyrosine kinase.
2011 Oct 27
Comprehensive analysis of kinase inhibitor selectivity.
2011 Oct 30
A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery.
2013 Apr 15
Patents

Patents

Sample Use Guides

50 mg twice daily for 14 days
Route of Administration: Oral
100 nM PKC412 treatment for 24 h induced the activation of caspase-3 and subsequently inactive the activity of PARP. Moreover, PKC412 treatment showed the inhibition of survivin, XIAP and Bcl-2 expression. The PKC412-induced apoptosis is further supported by the morphology findings that PKC412 treatment show the DNA damage and appearance of apoptotic bodies in IMS-M2 cells.
Substance Class Chemical
Created
by admin
on Fri Jun 25 22:02:46 UTC 2021
Edited
by admin
on Fri Jun 25 22:02:46 UTC 2021
Record UNII
ID912S5VON
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
MIDOSTAURIN
INN   MART.   MI   USAN   WHO-DD  
INN   USAN  
Official Name English
MIDOSTAURIN [ORANGE BOOK]
Common Name English
CGP 41251
Code English
PKC 412
Code English
NSC-656576
Code English
RYDAPT
Brand Name English
MIDOSTAURIN [INN]
Common Name English
CGP-41251
Code English
MIDOSTAURIN [MI]
Common Name English
N-((9S,10R,11R,13R)-10-METHOXY-9-METHYL-1-OXO-2,3,10,11,12,13-HEXAHYDRO-9,13-EPOXY-1H,9H-DIINDOLO(1,2,3-GH:3',2',1'-LM)PYRROLO(3,4-J)(1,7)BENZODIAZONIN-11-YL)-N-METHYLBENZAMIDE
Common Name English
NVP-PKC412
Code English
PKC-412
Code English
MIDOSTAURIN [USAN]
Common Name English
MIDOSTAURIN [MART.]
Common Name English
MIDOSTAURIN [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C1742
Created by admin on Fri Jun 25 22:02:46 UTC 2021 , Edited by admin on Fri Jun 25 22:02:46 UTC 2021
EU-Orphan Drug EU/3/10/765
Created by admin on Fri Jun 25 22:02:46 UTC 2021 , Edited by admin on Fri Jun 25 22:02:46 UTC 2021
FDA ORPHAN DRUG 306410
Created by admin on Fri Jun 25 22:02:46 UTC 2021 , Edited by admin on Fri Jun 25 22:02:46 UTC 2021
WHO-ATC L01XE39
Created by admin on Fri Jun 25 22:02:46 UTC 2021 , Edited by admin on Fri Jun 25 22:02:46 UTC 2021
NCI_THESAURUS C2089
Created by admin on Fri Jun 25 22:02:46 UTC 2021 , Edited by admin on Fri Jun 25 22:02:46 UTC 2021
NDF-RT N0000175605
Created by admin on Fri Jun 25 22:02:46 UTC 2021 , Edited by admin on Fri Jun 25 22:02:46 UTC 2021
FDA ORPHAN DRUG 285909
Created by admin on Fri Jun 25 22:02:46 UTC 2021 , Edited by admin on Fri Jun 25 22:02:46 UTC 2021
Code System Code Type Description
INN
7677
Created by admin on Fri Jun 25 22:02:46 UTC 2021 , Edited by admin on Fri Jun 25 22:02:46 UTC 2021
PRIMARY
ChEMBL
CHEMBL608533
Created by admin on Fri Jun 25 22:02:46 UTC 2021 , Edited by admin on Fri Jun 25 22:02:46 UTC 2021
PRIMARY
DRUG CENTRAL
5231
Created by admin on Fri Jun 25 22:02:46 UTC 2021 , Edited by admin on Fri Jun 25 22:02:46 UTC 2021
PRIMARY
RXCUI
1919083
Created by admin on Fri Jun 25 22:02:46 UTC 2021 , Edited by admin on Fri Jun 25 22:02:46 UTC 2021
PRIMARY
NCI_THESAURUS
C1872
Created by admin on Fri Jun 25 22:02:46 UTC 2021 , Edited by admin on Fri Jun 25 22:02:46 UTC 2021
PRIMARY
PUBCHEM
9829523
Created by admin on Fri Jun 25 22:02:46 UTC 2021 , Edited by admin on Fri Jun 25 22:02:46 UTC 2021
PRIMARY
CAS
120685-11-2
Created by admin on Fri Jun 25 22:02:46 UTC 2021 , Edited by admin on Fri Jun 25 22:02:46 UTC 2021
PRIMARY
FDA UNII
ID912S5VON
Created by admin on Fri Jun 25 22:02:46 UTC 2021 , Edited by admin on Fri Jun 25 22:02:46 UTC 2021
PRIMARY
DRUG BANK
DB06595
Created by admin on Fri Jun 25 22:02:46 UTC 2021 , Edited by admin on Fri Jun 25 22:02:46 UTC 2021
PRIMARY
MESH
C411007
Created by admin on Fri Jun 25 22:02:46 UTC 2021 , Edited by admin on Fri Jun 25 22:02:46 UTC 2021
PRIMARY
LACTMED
Midostaurin
Created by admin on Fri Jun 25 22:02:46 UTC 2021 , Edited by admin on Fri Jun 25 22:02:46 UTC 2021
PRIMARY
EVMPD
SUB21040
Created by admin on Fri Jun 25 22:02:46 UTC 2021 , Edited by admin on Fri Jun 25 22:02:46 UTC 2021
PRIMARY
MERCK INDEX
M7534
Created by admin on Fri Jun 25 22:02:46 UTC 2021 , Edited by admin on Fri Jun 25 22:02:46 UTC 2021
PRIMARY Merck Index
WIKIPEDIA
Midostaurin
Created by admin on Fri Jun 25 22:02:46 UTC 2021 , Edited by admin on Fri Jun 25 22:02:46 UTC 2021
PRIMARY
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