Comparison

Wortmannin European Partner

Item no. S2758-5
Manufacturer Selleckchem
CASRN 19545-26-7
Amount 5 mg
Quantity options 10 mg 100 mg 1 g 10 g 10 mM/1 mL 20 mg 5 mg 5 g
Category
Type 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
Available
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)-

Note: The presented information and documents (Manual, Product Datasheet, Safety Datasheet and Certificate of Analysis) correspond to our latest update and should serve for orientational purpose only. We do not guarantee the topicality. We would kindly ask you to make a request for specific requirements, if necessary.

All products are intended for research use only (RUO). Not for human, veterinary or therapeutic use.

Amount: 5 mg
Available: In stock
available

Compare

Add to wishlist

Get an offer

Request delivery time

Ask a technical question

Submit a bulk request

Questions about this Product?