Wortmannin

Modify Date: 2024-01-02 14:52:23

Wortmannin Structure
Wortmannin structure
 Common Name Wortmannin
CAS Number 19545-26-7 Molecular Weight 428.432
Density 1.4±0.1 g/cm3 Boiling Point 615.6±55.0 °C at 760 mmHg
Molecular Formula C23H24O8 Melting Point 234-240ºC
MSDS USA Flash Point 326.1±31.5 °C
Symbol GHS06
GHS06		 Signal Word Danger

 Use of Wortmannin


Wortmannin is a multi-target inhibitor of PI3K and MLCK with IC50s of 3 nM and 200 nM, respectively. Wortmannin is also a potent inhibitor of DNA-PK (IC50, 16 nM) and ATM (IC50, 150 nM). Wortmannin is also a potent inhibitor of Polo-like kinase (Plk).

 Names

Name wortmannin
Synonym More Synonyms

 Wortmannin Biological Activity

Description Wortmannin is a multi-target inhibitor of PI3K and MLCK with IC50s of 3 nM and 200 nM, respectively. Wortmannin is also a potent inhibitor of DNA-PK (IC50, 16 nM) and ATM (IC50, 150 nM). Wortmannin is also a potent inhibitor of Polo-like kinase (Plk).
Related Catalog
Target

PI3K:3 nM (IC50)

ATM:150 nM (IC50)

ATR:1.8 μM (IC50)

DNA-PK:16 nM (IC50)

MLCK:200 nM (IC50)

Plk3:48 nM (IC50)

In Vitro 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[1]. In intact A549 lung adenocarcinoma cells, wortmannin inhibits both DNA-PK and ATM at concentrations that correlated closely with those required for radiosensitization. Furthermore, pretreatment of A549 cells with wortmannin results in radioresistant DNA synthesis, a characteristic abnormality of ATM-deficient cells[2]. 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[3]. Wortmannin is also a potent inhibitor of Polo-like kinase 3 (Plk3). Wortmannin potently inhibits the activity of purified Plk3 with an IC50 of 48 nM. Wortmannin is a potent inhibitor of Plk1 and AX7503, a tetramethylrhodamine-Wortmannin conjugate, is an activity-dependent probe for labeling Plk1. Wortmannin inhibits Plk1-AX7503 reactivity with a IC50 of 5.8 nM. Wortmannin inhibits Plk3 reacting with AX7503 in a dose-dependent manner. The IC50 value of Wortmannin for inhibiting labeling of Plk3 by AX7503 is determined to be 49 nM. Wortmannin covalently labels Plk1 and Plk3 by targeting conserved lysine residues in their ATP binding sites. Wortmannin inhibits Plk1 and Plk3 with a potency similar to its inhibition of PI3K. Wortmannin also inhibits Plk2 and Plk4[6].
In Vivo 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 inhibits tumor growth in orthotopic tumor, while both monotherapy can not[4]. Wortmannin (1 mg/kg) inhibits peritoneal metastasis of SW1990 in mice, without any weight loss[5].
Kinase Assay MLCK activity is assayed with peptide substrate (KKRPQRATSNVFS-NH2) or myosin light chain. The peptide substrate (24 μM) is phosphorylated in a reaction mixture containing 25 mM Tris-HC1 (pH 7.5), 0.5 mg/mL bovine serum albumin, 4 mM MgCl2, 0.5 mM CaCl2, 2.6 nM calmodulin, 1.5 nM MLCK, and 400 μM ATP in a final volume of 0.25 mL. After a 10-min preincubation at 28°C without ATP, the reaction is started by addition of ATP at 28°C and terminated by the addition of 0.1 mL of 10% (v/v) acetic acid after 30 min. The mixture is analyzed by high performance liquid chromatography: column, Unisil Pack 5C18 4.6 X 150 mm; solvent, 18% (v/v) acetonitrile, 0.1% (v/v) trifluoroacetic acid in water; flow rate, 1.0 mL/min; temperature, 40°C; detection, absorbance at 220 nm. Percent of reaction is calculated from the ratio of peak areas of phosphorylated form to those of unphosphorylated form. Specific activity measured under the conditions described above is 0.81 μmol/min/mg. Myosin light chain (108 μg/mL) is phosphorylated in a reaction mixture containing 25 mM Tris-HC1 (pH 7.5), 0.5 mg/mL bovine serum albumin, 4 mM MgCl2, 0.5 mM CaCl2, 4.2 nM calmodulin, 0.92 nM enzyme, and 10 μM[γ-32P]ATP (100-900 cpm/pmol) in a final volume of 0.25 mL. After a 3-min preincubation at 30°C without ATP, the reaction is started by the addition of [γ-32P]ATP at 30°C and stopped by the addition of 0.125 mL of trichloroacetic acid after 5 min. The acid-precipitable materials are collected on a nitrocellulose membrane filter and washed with four 1-mL aliquots of 5% (v/v) trichloroacetic acid. The radioactivity on the filter is measured in a toluene scintillation fluid, using a Packard Tri-Carb liquid scintillation spectrometer Model 4530. The specific activity measured under the conditions is 1.23 μmol/min/mg.
Animal Admin Specific pathogen-free athymic BALB/c male mice (5 weeks) are kept under sterile conditions in a laminar flow room in cages with filter bonnets and fed a sterilized mouse diet and water. In order to induce peritoneal metastasis, the mice are anesthetized by inhalation administration of sevoflurane, and SW1990 cells (1×106 cells/mouse) in 100 μL of PBS are injected into the peritoneal cavity using a 23-gauge needle after incubation without FBS for 24 h to inactivate Akt. To examine the effect of PI3K inhibitor, the mice are treated with the intraperitoneal treatment of wortmannin at 1.0, 0.5, or 0.25 mg/kg/day or vehicle (PBS + dimethyl sulfoxide) immediately after cancer cells are inoculated. The treatment is continued for 20 consecutive days. Twenty days later, mice are sacrificed and body weight, ascites, number, and total weight of peritoneal metastatic tumors are examined. The weight exceeding the mean weight of mesenterium and greater omentum of normal nude mice of the same age (in weeks) is regarded as the net weight of metastatic tumors in order to minimize the interfusion of blood or tissues.
References

[1]. Yano H, et al. Inhibition of histamine secretion by wortmannin through the blockade of phosphatidylinositol 3-kinase in RBL-2H3 cells. J Biol Chem, 1993, 268(34), 25846-25856.

[2]. Sarkaria JN, et al. Inhibition of phosphoinositide 3-kinase related kinases by the radiosensitizing agent wortmannin. Cancer Res, 1998, 58(19), 4375-4382.

[3]. Nakanishi S, et al. Wortmannin, a microbial product inhibitor of myosin light chain kinase. J Biol Chem, 1992, 267(4), 2157-2163.

[4]. Ng SS, et al. Wortmannin inhibits pkb/akt phosphorylation and promotes gemcitabine antitumor activity in orthotopic human pancreatic cancer xenografts in immunodeficient mice. Clin Cancer Res, 2001, 7(10), 3269-3275.

[5]. Teranishi F, et al. Phosphoinositide 3-kinase inhibitor (wortmannin) inhibits pancreatic cancer cell motility and migration induced by hyaluronan in vitro and peritoneal metastasis in vivo. Cancer Sci. 2009 Apr;100(4):770-7.

[6]. Liu Y, et al. Polo-like kinases inhibited by Wortmannin. Labeling site and downstream effects. J Biol Chem. 2007 Jan 26;282(4):2505-11.

 Chemical & Physical Properties

Density 1.4±0.1 g/cm3
Boiling Point 615.6±55.0 °C at 760 mmHg
Melting Point 234-240ºC
Molecular Formula C23H24O8
Molecular Weight 428.432
Flash Point 326.1±31.5 °C
Exact Mass 428.147125
PSA 109.11000
LogP 0.81
Vapour Pressure 0.0±1.8 mmHg at 25°C
Index of Refraction 1.591
Storage condition 2-8°C
Water Solubility DMSO: soluble

 Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :
CB9641000
CHEMICAL NAME :
Antibiotic SL-2052
CAS REGISTRY NUMBER :
19545-26-7
BEILSTEIN REFERENCE NO. :
0067676
LAST UPDATED :
199612
DATA ITEMS CITED :
2
MOLECULAR FORMULA :
C23-H24-O8
MOLECULAR WEIGHT :
428.47

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :
LDLo - Lowest published lethal dose
ROUTE OF EXPOSURE :
Oral
SPECIES OBSERVED :
Rodent - rat
DOSE/DURATION :
10 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
EXPEAM Experientia. (Birkhaeuser Verlag, POB 133, CH-4010 Basel, Switzerland) V.1- 1945- Volume(issue)/page/year: 30,135,1974
TYPE OF TEST :
LD50 - Lethal dose, 50 percent kill
ROUTE OF EXPOSURE :
Intraperitoneal
SPECIES OBSERVED :
Rodent - mouse
DOSE/DURATION :
18 mg/kg
TOXIC EFFECTS :
Details of toxic effects not reported other than lethal dose value
REFERENCE :
85GDA2 "CRC Handbook of Antibiotic Compounds," Vols.1- , Berdy, J., Boca Raton, FL, CRC Press, 1980- Volume(issue)/page/year: 6,168,1981

 Safety Information

Symbol GHS06
GHS06
Signal Word Danger
Hazard Statements H300-H310-H330
Precautionary Statements P260-P264-P280-P284-P302 + P350-P310
Personal Protective Equipment Eyeshields;Faceshields;full-face particle respirator type N100 (US);Gloves;respirator cartridge type N100 (US);type P1 (EN143) respirator filter;type P3 (EN 143) respirator cartridges
Hazard Codes T+: Very toxic;T: Toxic;
Risk Phrases R26/27/28
Safety Phrases 28-36/37-45
RIDADR UN 3462
WGK Germany 3
RTECS CB9641000
Packaging Group I
Hazard Class 6.1

 Synthetic Route

 Articles289

More Articles
Pro-apoptotic and pro-autophagic effects of the Aurora kinase A inhibitor alisertib (MLN8237) on human osteosarcoma U-2 OS and MG-63 cells through the activation of mitochondria-mediated pathway and inhibition of p38 MAPK/PI3K/Akt/mTOR signaling pathway.

Drug Des. Devel. Ther. 9 , 1555-84, (2015)

Osteosarcoma (OS) is the most common malignant bone tumor occurring mostly in children and adolescents between 10 and 20 years of age with poor response to current therapeutics. Alisertib (ALS, MLN823...

SUMO1 promotes Aβ production via the modulation of autophagy.

Autophagy 11(1) , 100-12, (2015)

Autophagy is one of the main mechanisms in the pathophysiology of neurodegenerative disease. The accumulation of autophagic vacuoles (AVs) in affected neurons is responsible for amyloid-β (Aβ) product...

Unmethylated CpG motifs in the L. donovani DNA regulate TLR9-dependent delay of programmed cell death in macrophages.

J. Leukoc. Biol. 97(2) , 363-78, (2015)

Regulation of macrophage PCD plays an important role in pathogenesis of leishmaniasis. However, the precise involvement of any parasite molecule in this process remains uncertain. In the current study...

 Synonyms

EINECS 214-538-0
Wartmannin
MFCD00133927
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)-
(1S,6BR,9AS,11R,11BR)-9A,11B-DIMETHYL-1-[(METHYLOXY)METHYL]-3,6,9-TRIOXO-1,6,6B,7,8,9,9A,10,11,11B-DECAHYDRO-3H-FURO[4,3,2-DE]INDENO[4,5-H][2]BENZOPYRAN-11-YL ACETATE
Wortmannin
SL-2052
Antibiotic SL-2052
(1S,6bR,9aS,11R,11bR)-1-(Methoxymethyl)-9a,11b-dimethyl-3,6,9-trioxo-1,6,6b,7,8,9,9a,10,11,11b-decahydro-3H-furo[4,3,2-de]indeno[4,5-h]isochromen-11-yl acetate
Top Suppliers:I want be here

Get all suppliers and price by the below link:

Wortmannin suppliers

Price: $106/10mM*1mLinDMSO

Reference only. check more Wortmannin price

Related Compounds: More...
17-OH wortmannin
58053-83-1
17-Hydroxywortmannin
108740-89-2
11-desacetoxywortmannin
31652-69-4
Wortmannin-Rapamycin Conjugate
1067892-47-0
4-((Cyclohexylamino)methyl)benzoic acid hydrochloride
1158522-08-7
1-[(2,4-Dichlorophenyl)methyl]-N-(1,1-dimethylethyl)-2-methyl-1H-indole-3-methanamine
940364-43-2
2-Methoxy-6-(pyrazol-1-yl)-benzonitrile
134104-43-1
1H-3-Benzazepin-7-ol, 8-chloro-2,3,4,5-tetrahydro-5-(3-iodophenyl)-3-methyl-, (S)-
131615-57-1
4-[(1,2,4-Oxadiazol-3-yl)methyl]piperidine hydrochloride
2126176-79-0
(4-Methyl-tetrahydro-furan-2-yl)-methanol
6906-52-1
N-(1-cyanocyclopentyl)-2-[4-(4-fluorobenzenesulfonyl)-1,4-diazepan-1-yl]acetamide
930439-75-1
4-Amino-8-iodo-1,2,3,4-tetrahydroquinolin-3-ol
1823324-05-5
1-[4-(4-Methoxybenzyloxy)-3-nitrophenyl]ethanone
2204588-03-2
4,5,6,7-Tetrahydrobenzo[d]isoxazole-3-carbaldehyde
1018584-77-4
Chemsrc provides Wortmannin(CAS#:19545-26-7) MSDS, density, melting point, boiling point, structure, formula, molecular weight etc. Articles of Wortmannin are included as well.>> amp version: Wortmannin

Home | MSDS/SDS Database Search | Journals | Product Classification | Biologically Active Compounds | Selling Leads | About Us | Disclaimer

Copyright © 2024 ChemSrc All Rights Reserved