Wortmannin (KY 12420) - Moligand™, 10mM in DMSO , Inhibitor of mechanistic target of rapamycin kinase;Inhibitor of phosphatidylinositol-4;5-bisphosphate 3-kinase catalytic subunit alpha;Inhibitor of phosphatidylinositol-4;5-bisphosphate 3-kinase catalytic, Inhibitor of mechanistic target of rapamycin kinase;Inhibitor of phosphatidylinositol-4;5-bisphosphate 3-kinase catalytic subunit alpha;Inhibitor of phosphatidylinositol-4;5-bisphosphate 3-kinase catalytic subunit beta;Inhibitor of phosphatidylinositol-4;

CAS: 19545-26-7 Cat. No.: W409260 Molecular Weight: 428.43 Beilstein Registry Number: 67676 EC Number: 606-337-5 PubChem CID: 312145

GRADE & PURITY Moligand™, 10mM in DMSO

Synonyms

SL-2052, BRN 0067676, NSC 627609 | 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)-

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Overview

Information

Wortmannin (KY 12420, SL-2052, BRN 0067676, NSC 627609) is the first describedPI3Kinhibitor withIC50of 3 nM in a cell-free assay, with little selectivity within the PI3K family. Wortmannin blocksautophagosomeformation and potently inhibitsDNA-PK/ATMwithIC
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. 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. 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. Wortmannin completely abolishes the insulin-induced hexose uptake in isolated rat adipocytes at 0.1 μM, without impairing isoproterenol-stimulated lipolytic activity. 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. 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 μM. Wortmannin could potentiate ionizing radiation (IR)-induced cytotoxicity with no toxicity by itself. Wortmannin inhibits polo-like kinase (PLK1) activity IC50 of 24 nM in intact G2/M-arrested cells. 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-κB and up-regulates the cytokine mRNA production. 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. Wortmannin suppresses hyaluronan-induced Akt phosphorylation and cell motility/migration in SW1990 cells.

In vivo

Wortmannin inhibits peritoneal metastasis of SW1990 in mice at 1 mg/kg, without any weight loss. 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 LY188011, Wortmannin significantly increases apoptosis and inhibit tumor growth in orthotopic tumor, while both monotherapy could not.
Cell Data

cell lines：HeLa BRCA1-silenced cells

Concentrations：

Incubation Time：

Powder Purity:≥99%

Specifications

Synonyms

SL-2052, BRN 0067676, NSC 627609 | 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)-

Specifications & Purity

Moligand™, 10mM in DMSO

Biochemical and Physiological Mechanisms

Wortmannin (KY 12420, SL-2052, BRN 0067676, NSC 627609) 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/AT

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

This product requires cold chain shipping. Ground and other economy services are not available.

Grade

Moligand™

Action Type

INHIBITOR

Mechanism of action

Inhibitor of mechanistic target of rapamycin kinase;Inhibitor of phosphatidylinositol-4;5-bisphosphate 3-kinase catalytic subunit alpha;Inhibitor of phosphatidylinositol-4;5-bisphosphate 3-kinase catalytic subunit beta;Inhibitor of phosphatidylinositol-4;

Names and Identifiers

• Isomeric SMILES: CC(=O)O[C@@H]1C[C@]2([C@@H](CCC2=O)C3=C1[C@]4([C@H](OC(=O)C5=COC(=C54)C3=O)COC)C)C
• WGK Germany: 3
• RTECS: CB9641000
• PubChem CID: 312145
• UN Number: 3462
• Molecular Weight: 428.43
• Beilstein: 67676

Associated Targets(Human)

PRKDC Tchem DNA-dependent protein kinase catalytic subunit (1 Activities)

Discover Target: PRKDC

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

HSP90AA1 Tchem Heat shock protein HSP 90-alpha (1 Activities)

Discover Target: HSP90AA1

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

PIK3CG Tclin Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform (5 Activities)

Discover Target: PIK3CG

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

PIK3CA Tclin Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (10 Activities)

Discover Target: PIK3CA

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

PIK3CB Tchem Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform (5 Activities)

Discover Target: PIK3CB

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

PIK3CD Tclin Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (5 Activities)

Discover Target: PIK3CD

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

PLK1 Tchem Serine/threonine-protein kinase PLK1 (2 Activities)

Discover Target: PLK1

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

MTOR Tclin Serine/threonine-protein kinase mTOR (1 Activities)

Discover Target: MTOR

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

Chemical and Physical Properties

• Solubility: Solubility (25°C) In vitro
• Melt Point(°C): 237 °C

References

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