Midostaurin

Midostaurin, also known as PKC-412, PKC-412A and CGP 41251; is a synthetic indolocarbazole multikinase inhibitor with potential antiangiogenic and antineoplastic activities. Midostaurin inhibits protein kinase C alpha (PKCalpha), vascular endothelial growth factor receptor 2 (VEGFR2), c-kit, platelet-derived growth factor receptor (PDGFR) and FMS-like tyrosine kinase 3 (FLT3) tyrosine kinases, which may result in disruption of the cell cycle, inhibition of proliferation, apoptosis, and inhibition of angiogenesis in susceptible tumors. Midostaurin was approved in 2017.

Product information

CAS Number: 120685-11-2

Molecular Weight: 570.64

Formula: C35H30N4O4

Synonym:

PKC-412

PKC412A

CGP41251

Rydapt

Midostaurin

Chemical Name: N-((5R,7R,8R,9S)-8-methoxy-9-methyl-16-oxo-6,7,8,9,15,16-hexahydro-5H,14H-17-oxa-4b,9a,15-triaza-5,9-methanodibenzo[b,h]cyclonona[jkl]cyclopenta[e]-as-indacen-7-yl)-N-methylbenzamide

Smiles: CN([C@@H]1C[C@@H]2O[C@@](C)([C@@H]1OC)N1C3=C(C4=CC=CC=C14)C1CNC(=O)C=1C1=C3N2C2C=CC=CC=21)C(=O)C1C=CC=CC=1

InChiKey: BMGQWWVMWDBQGC-AKZXJVOYSA-N

InChi: 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

Technical Data

Appearance: Solid Power.

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Soluble in DMSO, not soluble in water.

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined.

HS Tariff Code: 382200

How to use

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. 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. 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.

In Vivo:

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

References:

1. Wang ES. Beyond midostaurin: Which are the most promising FLT3 inhibitors in AML? Best Pract Res Clin Haematol. 2019 Dec;32(4):101103. doi: 10.1016/j.beha.2019.101103. Epub 2019 Oct 18. Review. PubMed PMID: 31779982.
2. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Available from http://www.ncbi.nlm.nih.gov/books/NBK548874/ PubMed PMID: 31644181.
3. Midostaurin for acute myeloid leukaemia, mastocytosis, and mast cell leukaemia. Aust Prescr. 2019 Apr;42(2):73-74. doi: 10.18773/austprescr.2019.017. Epub 2019 Feb 28. Review. PubMed PMID: 31048943; PubMed Central PMCID: PMC6478956.
4. Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Available from http://www.ncbi.nlm.nih.gov/books/NBK500909/ PubMed PMID: 29999968.

Products are for research use only. Not for human use.