| Identification | Back Directory | [Name]
Midostaurin | [CAS]
120685-11-2 | [Synonyms]
QTH113
CS-730
CGP 41231
Cgp 41251
Cgp-41251
Cgp 41 251
Midaustorin
Midostaurin
midostaruin
Midostaurin [inn]
PKC-412, CGP-41251
Midostaurin (PKC412)
PKC412 (Midostaurin)
Benzoylstaurosporine
Midostaurin USP/EP/BP
N-Benzoylstaurosporine
Staurosporine, N-Benzoyl
PKC412 from Staurosporine
4'-N-benzoylstaurosporine
CGP 41251MIDOSTAURIN(PKC412)
MIDOSTAURIN (PKC412; CGP 41251)
(Midostaurin) Benzoylstaurosporine
PKC412(Midostaurin,CGP41231,CGP41251)
MIDOSTAURIN; CGP-41251; PKC-412; PKC412;PKC 412
Midostaurin, Benzoylstaurosporine, 4'-N-Benzoylstaurosporine, CGP 41251
PKC412 CGP 41231 CGP 41251 Midostaurin Benzoylstaurosporine
N-((5S,6R,7R,9R)-6-Methoxy-14-oxo-5,6,7,8,9,14,15,16-octahydro-17-oxa-4b,9a,15-triaza-5,9-Methanodibenzo[b,h]cyclonona[jkl]cyclopenta[e]-as-indacen-7-yl)-N-MethylbenzaMide
Benzamide, N-((9S,10R,11R,13R)-2,3,9,10,11,12-hexahydro-10-methoxy-9-methyl-1-oxo-9,13-epoxy-1H,9H-diindolo(1,2,3-gh:3',2',1'-lm)pyrrolo(3,4-J)(1,7)benzodiazonin-11-yl)-N-methyl-
Benzamide, N-(2,3,9,10,11,12-hexahydro-9-methoxy-8-methyl-1-oxo-8,12-epoxy-1H,8H-2,7B,12A-triazadibenzo(A,G)cyclonona(cde)trinden-10-yl)-N-methyl-, (8alpha,9beta,10beta,12alpha)-
Benzamide, N-[(9S,10R,11R,13R)-2,3,10,11,12,13-hexahydro-10-methoxy-9-methyl-1-oxo-9,13-epoxy-1H,9H-diindolo[1,2,3-gh:3',2',1'-lm]pyrrolo[3,4-j][1,7]benzodiazonin-11-yl]-N-methyl-
[9S-(9α,10β,11β,13α)]-N-(2,3,10,11,12,13-Hexahydro-10-methoxy-9-methyl-1-oxo-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 | [EINECS(EC#)]
999-999-2 | [Molecular Formula]
C35H30N4O4 | [MDL Number]
MFCD10687105 | [MOL File]
120685-11-2.mol | [Molecular Weight]
570.646 |
| Chemical Properties | Back Directory | [Melting point ]
235-260℃ | [density ]
1.47±0.1 g/cm3(Predicted) | [storage temp. ]
Store at 2-8 | [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. |
| Hazard Information | Back Directory | [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 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. | [Enzyme inhibitor]
This broad-spectrum serine/threonine/tyrosine protein kinase inhibitor
(PKI) and radiooncology sensitizing agent (FW = 570.65 g/mol; CAS
120685-11-2), also known as CGP 41251 and [9S- (9α,10β,11β,13α) ]-N-
(2,3,10,11,12,13-hexahydro-10-methoxy-9-methyl-1-oxo-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 targets conventional PKCα, PKCβ, PKCγ, PDFRβ,
VEGFR2, Syk, PKCη, Flk-1, Flt3, Cdk1/B, PKA, c-Kit, c-Fgr, c-Src,
VEGFR1 and EGFR, displaying potent antitumor activity (See also
AC220 & G-749). | [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 |
| Questions And Answer | Back Directory | [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).
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