ALEXIS Biochemicals: PKC412

ALX-380-281

Revised 20-Jun-08

PKC412
SYNONYMS	4’-N-Benzoyl-staurosporine Midostaurin CGP 41251
PRODUCT LINE	Natural Products / Antibiotics
PRODUCT CATEGORY	Natural Products - Protein Kinase Inhibitors

Ordering Information

Product Numbers:	Format:	Size:	Unit Price:	Quantity:	Add To Cart
ALX-380-281-M001		1 mg	60.00 USD
ALX-380-281-M005		5 mg	240.00 USD

Product Specification

FORMULA:	C₃₅H₃₀N₄O₄
MW:	570.6
CAS NUMBER:	120685-11-2
MERCK INDEX:	14: 6185
SOURCE/HOST:	Semisynthetic product prepared from staurosporine (a fermentation product of Streptomyces staurosporeus) (Prod. No. ALX-380-014).
PURITY:	≥96% (HPLC)
APPEARANCE:	White to off-white powder.
SOLUBILITY:	Soluble in DMSO (10mg/ml), MDC (10mg/ml) or methanol (5mg/ml).
SHIPPING:	AMBIENT
LONG TERM STORAGE:	-20°C

Product Description

Inhibitor of a variety of serine/threonine and tyrosine kinases, like protein kinase C (PKC), cyclic AMP-dependent protein kinase (PKA), S6 kinase, Akt (protein kinase B; PKB) and epidermal growth factor receptor (EGFR) tyrosine kinase activity. Potently inhibits FLT-3 kinase in vitro and in vivo. Apoptosis inducer. Showed broad antiproliferative activity against various tumor cell lines. Selectively inhibits T lymphocyte production of TNF-α. Upregulates endothelial nitric oxide synthase (eNOS; NOS III).

Product Specific Literature References

Differential inhibition of the epidermal growth factor-, platelet-derived growth factor-, and protein kinase C-mediated signal transduction pathways by the staurosporine derivative CGP 41251: E. Andrejauskas-Buchdunger & U. Regenass; Cancer Res. 52, 5353 (1992) Abstract; Full Text
Analogs of staurosporine: potential anticancer drugs?: A. Gescher; Gen. Pharmacol. 31, 721 (1998), (Review) Abstract
Differential effects of UCN-01, staurosporine and CGP 41 251 on cell cycle progression and CDC2/cyclin B1 regulation in A431 cells synchronized at M phase by nocodazole: T. Akiyama, et al.; Anticancer Drugs 10, 67 (1999) Abstract
Inhibitors of protein kinases: CGP 41251, a protein kinase inhibitor with potential as an anticancer agent: D. Fabbro, et al.; Pharmacol. Ther. 82, 293 (1999) Abstract
The phosphatidylinositide 3’-kinase/Akt survival pathway is a target for the anticancer and radiosensitizing agent PKC412, an inhibitor of protein kinase C: A. Tenzer, et al.; Cancer Res. 61, 8203 (2001) Abstract; Full Text
Phase I and pharmacokinetic study of PKC412, an inhibitor of protein kinase C: D.J. Propper, et al.; J. Clin. Oncol. 19, 1485 (2001) Abstract; Full Text
A protein kinase C inhibitor induces phenotypic reversion of ras-transformed pancreatic cancer cells and cooperatively blocks tumor cell proliferation with an anti- ras peptide.: D. Way, et al.; Cancer Chemother. Pharmacol. 49, 429 (2002) Abstract
Protein kinase C inhibitors: H.C. Swannie & S.B. Kaye; Curr. Oncol. Rep. 4, 37 (2002), (Review) Abstract
PKC412 inhibits the zinc finger 198-fibroblast growth factor receptor 1 fusion tyrosine kinase and is active in treatment of stem cell myeloproliferative disorder: J. Chen, et al.; PNAS 101, 14479 (2004) Abstract; Full Text
Cotreatment with 17-allylamino-demethoxygeldanamycin and FLT-3 kinase inhibitor PKC412 is highly effective against human acute myelogenous leukemia cells with mutant FLT-3: P. George, et al.; Cancer Res. 64, 3645 (2004) Abstract; Full Text
Effects of the kinase inhibitor CGP41251 (PKC 412) on lymphocyte activation and TNF-alpha production: M.S. Si, et al.; Int. Immunopharmacol. 5, 1141 (2005) Abstract
N-Benzoylstaurosporine (PKC412) inhibits Akt kinase inducing apoptosis in multiple myeloma cells.: N.J. Bahlis, et al.; Leuk. Lymphoma 46, 899 (2005) Abstract
Midostaurin upregulates eNOS gene expression and preserves eNOS function in the microcirculation of the mouse: H. Li, et al.; Nitric Oxide 12, 231 (2005) Abstract
Inhibitors of the PI3-kinase/Akt pathway induce mitotic catastrophe in non-small cell lung cancer cells: T.H. Hemström, et al.; Int. J. Cancer 119, 1028 (2006) Abstract
Antitumor and normal cell protective effect of PKC412 in the athymic mouse model of ovarian cancer: M. Kim, et al.; Ann. Clin. Lab. Sci. 36, 455 (2006) Abstract
PKC412 inhibits in vitro growth of neoplastic human mast cells expressing the D816V-mutated variant of KIT: comparison with AMN107, imatinib, and cladribine (2CdA) and evaluation of cooperative drug effects.: K.V. Gleixner, et al.; Blood 107, 752 (2006) Abstract; Full Text
Synergistic growth-inhibitory effects of two tyrosine kinase inhibitors, dasatinib and PKC412, on neoplastic mast cells expressing the D816V-mutated oncogenic variant of KIT: K.V. Gleixner, et al.; Haematologica 92, 1451 (2007) Abstract; Full Text
PKC 412 small-molecule tyrosine kinase inhibitor: single-compound therapy for pancreatic cancer: J. El Fitori, et al.; Cancer 110, 1457 (2007) Abstract
PKC412 (CGP41251) modulates the proliferation and lipopolysaccharide-induced inflammatory responses of RAW 264.7 macrophages: K. Miyatake, et al.; BBRC 360, 115 (2007) Abstract
Divergent cytotoxic effects of PKC412 in combination with conventional antileukemic agents in FLT3 mutation-positive versus -negative leukemia cell lines.: Y. Furukawa, et al.; Leukemia 21, 1005 (2007) Abstract
PKC412 demonstrates JNK-dependent activity against human multiple myeloma cells: J. Sharkey, et al.; Blood 109, 1712 (2007) Abstract
The FLT3 inhibitor PKC412 exerts differential cell cycle effects on leukemic cells depending on the presence of FLT3 mutations: T. Odgerel, et al.; Oncogene 27, 3102 (2008) Abstract
The FLT3 inhibitor PKC412 in combination with cytostatic drugs in vitro in acute myeloid leukemia: L. Möllgard, et al.; Cancer Chemother. Pharmacol. 62, 439 (2008) Abstract