Vergleich

Wortmannin Europäischer Partner

ArtNr S2758-20
Hersteller Selleckchem
CAS-Nr. 19545-26-7
Menge 20 mg
Quantity options 10 mg 100 mg 1 g 10 g 10 mM/1 mL 20 mg 5 mg 5 g
Kategorie
Typ Inhibitors
Specific against other
Smiles CC(=O)OC1CC2(C(CCC2=O)C3=C1C4(C(OC(=O)C5=COC(=C54)C3=O)COC)C)C
ECLASS 10.1 32160490
ECLASS 11.0 32160490
UNSPSC 12000000
Alias KY 12420,SL-2052,BRN 0067676,NSC 627609
Similar products Wortmannin
Lieferbar
Manufacturer - Targets
PI3K
Storage Conditions
2 years -80 in solvent
Molecular Weight
428, 43
Administration
Injected by i.v.
Animal Models
Human pancreatic adenocarcinoma cells PK1 are injected both s.c. and orthotopically into SCID mice.
Clinical Trials
Phase IV clinical trial has been completed in relapsing multiple sclerosis patients treated with Interferon beta-1a.
Dosages
0.175, 0.35, and 0.7 mg/kg
Formulation
Dissolved at 0.4 mg/mL in DMSO, and diluted with 0.9% NaCl before use
IC50
0.17 uM [1], 0.17 uM [1], 0.17 uM [1], 0.17 uM [1], 0.17 uM [1], 0.17 uM [1]
In vitro
The inhibition of MLCK by Wortmannin is not affected by calmodulin or peptide substrat, while reduced by high concentration of ATP. Wortmannin directly interacts with the catalytic domain of MLCK and leads to an irreversible loss of the enzyme activity. Wortmannin has no inhibitory to cAMP-dependent protein kinase, cGMP-dependent protein kinase, and calmodulin-dependent protein kinase II, and has little effect on protein kinase C activity. [1] Wortmannin inhibits N-formylmethionyl-leucylphenylalanine (fMLP)-stimulated PtdInsP3 (phosphatidylinositol 3, 4, 5-trisphosphate) formation with IC50 of 5 nM and this inhibition is completely abolished when pretreated with 100 nM Wortmannin in human neutrophils, with increased PtdInsP2 levels and no effects on cellular PtdInsP and PtdIns contents. Wortmannin could develop oscillatory changes in F-actin content and does not inhibit fMLP-stimulated actin polymerization in neutrophils. [2] Wortmannin irreversibly inhibits phosphatidylinositol 3-kinase (PI3-kinase) activity with binding to the 110-kDa protein (IC50 of 3 nM) and has no effect PI4-kinase in RBL-2H3 cells. Wortmannin also inhibits both Fc epsilon RI-mediated histamine secretion and leukotriene release, with no effect on the activation of the tyrosine kinase Lyn. [3] Wortmannin completely abolishes the insulin-induced hexose uptake in isolated rat adipocytes at 0.1 uM, without impairing isoproterenol-stimulated lipolytic activity., [4] Wortmannin suppresses insulin-induced production of nitric oxide by 50% at 500 nM in human umbilical vein endothelial cells, which is in response to IGF-1. [5] Wortmannin suppresses DNA double strand break (DSB) repair and has no effect on DSB levels or the kinetics of single strand break (SSB) repair in Chinese hamster ovary cells at 50 uM. Wortmannin could potentiate ionizing radiation (IR)-induced cytotoxicity with no toxicity by itself. [6] Wortmannin inhibits polo-like kinase (PLK1) activity IC50 of 24 nM in intact G2/M-arrested cells. [7] Wortmannin increases Toll-like receptor (TLR)-mediated accumulation of IL-6 in human macrophages with EC50 of 50 nM. Meanwhile Wortmannin significantly enhances TLR-mediated inducible nitric-oxide synthase (iNOS) expression and nitrite accumulation in mouse macrphages. Wortmannin activates the nuclear factor-kappaB and up-regulates the cytokine mRNA production. [8] Wortmannin also inhibits Polo-like kinase (PlK) 1 and PlK3, which play important roles in mitosis. Wortmannin treatment could lead to a reduction in phosphorylation of p53 on serine 20 induced by DNA damage. [9] Wortmannin suppresses hyaluronan-induced Akt phosphorylation and cell motility/migration in SW1990 cells. [10]
In vivo
Wortmannin inhibits peritoneal metastasis of SW1990 in mice at 1 mg/kg, without any weight loss. [10], Wortmannin inhibits phosphatidylinositide 3-kinase-protein kinase B (PKB)/Akt phosphorylation in both normal tissues (lung, heart and brain homogenates) and tumor tissue in mice, without mortality or acute toxicity at 0.7 mg/kg. Combination with gemcitabine, Wortmannin significantly increases apoptosis and inhibit tumor growth in orthotopic tumor, while both monotherapy could not. [11]
Solubility (25C)
DMSO 86 mg/mL, Water <1 mg/mL, Ethanol <1 mg/mL
Information
Wortmannin is the first described PI3K inhibitor with IC50 of 3 nM in a cell-free assay, with little selectivity within the PI3K family. Wortmannin blocks autophagosome formation and potently inhibits DNA-PK/ATM with IC50 of 16 nM and 150 nM in cell-free assays. Wortmannin also inhibits PLK1 activity.
Chemical Name
3H-Furo[4, 3, 2-de]indeno[4, 5-h]-2-benzopyran-3, 6, 9-trione, 11-(acetyloxy)-1, 6b, 7, 8, 9a, 10, 11, 11b-octahydro-1-(methoxymethyl)-9a, 11b-dimethyl-, (1S, 6bR, 9aS, 11R, 11bR)-

Hinweis: Die dargestellten Informationen und Dokumente (Bedienungsanleitung, Produktdatenblatt, Sicherheitsdatenblatt und Analysezertifikat) entsprechen unserem letzten Update und sollten lediglich der Orientierung dienen. Wir übernehmen keine Garantie für die Aktualität. Für spezifische Anforderungen bitten wir Sie, uns eine Anfrage zu stellen.

Alle Produkte sind nur für Forschungszwecke bestimmt. Nicht für den menschlichen, tierärztlichen oder therapeutischen Gebrauch.

Menge: 20 mg
Lieferbar: In stock
lieferbar

Vergleichen

Auf den Wunschzettel

Angebot anfordern

Lieferzeit anfragen

Technische Frage stellen

Bulk-Anfrage stellen

Fragen zum Produkt?