Midostaurin Chemical Properties

Melting point:

235-260℃

Density 

1.47±0.1 g/cm3(Predicted)

storage temp. 

Sealed in dry,Store in freezer, under -20°C

solubility 

Soluble in DMSO (15 mg/ml), MDC (10 mg/ml), methanol (5 mg/ml), 100% ethanol (2.5 mg/ml), and DMF (20 mg/ml).

form 

Tan solid

pka

14.19±0.70(Predicted)

color 

White

Stability:

Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 2 months.

Safety Information

Hazard Codes 

T

Risk Statements 

36/37/38

HS Code 

29329990

Midostaurin Usage And Synthesis

Binding Mode

The only available X-ray co-crystal structure of midostaurin is in complex with DYRK1A (dual specificity tyrosine phosphorylation regulated kinase 1A)(Fig.1). Midostaurin is anchored to the hinge with two hydrogen bonds: the lactam NH with amide carbonyl of Glu239; and the lactam carbonyl with amide NH of Leu241 (Fig.2).

Description

PKC-412 (120685-11-2) is a broad spectrum kinase inhibitor. Inhibited kinases include, but are not limited to; PKA, PKC, S6 Kinase, KDR, PKC, Akt, EGFR, VEGFR, PDGFR, c-kit, and FLT-3. Acute myeloid leukemia related mutant forms of FLT-3 are also inhibited both in vitro and in vivo. PKC-412 has been demonstrated to induce apoptosis and shows broad antiproliferative activity in various tumor cell lines. Cell Permeable

Uses

Midostaurin is used as a broad spectrum protein kinase inhibitor. Inhibits conventional PKC isoforms (α, β, γ), PDFRβ, VEGFR2, Syk, PKCη, Flk-1, Flt3, Cdk1/B, PKA, c-Kit, c-Fgr, c-Src, VEGFR1 and EGFR. Displays potent antitumor activity. Due to this act which may result in disruption of the cell cycle, inhibition of proliferation, apoptosis, and inhibition of angiogenesis in susceptible tumors. Midostaurin was shown to possess antiproliferative characteristics via inhibition of protein kinase C, kinase insert domain receptor, and c-kit.

Definition

ChEBI: An organic heterooctacyclic compound that is the N-benzoyl derivative of staurosporine.

brand name

Rydapt

General Description

Class: receptor tyrosine kinase; Treatment: AML, SM; Other name: PKC-412, CGP41251; Elimination half-life = 20 h; Protein binding > 99%

Biological Activity

Broad spectrum protein kinase inhibitor. Inhibits conventional PKC isoforms ( α , β , γ ), PDFR β , VEGFR2, Syk, PKCη, Flk-1, Flt3, Cdk1/B, PKA, c-Kit, c-Fgr, c-Src, VEGFR1 and EGFR. Displays potent antitumor activity.

target

Primary targets: FLT3, KIT

storage

Store at -20°C

References

1) Odgerel et al. (2008) The FLT3 inhibitor PKC412 exerts differential cell cycle effects on leukemic cells depending on the presence of FLT3 mutations; Oncogene, 27 3102 2) El Fitori et al. (2007) PKC 412 small-molecule tyrosine kinase inhibitor: single-compound therapy for pancreatic cancer; Cancer, 110 1457 3) Miyatake, et al. ( 2007) PKC412 (CGP41251) modulates the proliferation and lipopolysaccharide-induced inflammatory responses of RAW 264.macrophages; Biochem. Biophys. Res. Commun., 360 115 4) Bahlis et.al. (2005) N-Benzoylstaurosporine (PKC412) inhibits Akt kinase inducing apoptosis in multiple myeloma cells; Leuk. Lymphoma, 46 899 5) Fabbro et al., (2000) PKC-412 – a protein kinase inhibitor with a broad therapeutic potential; Anticancer Drug Des., 15 17

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