Wortmannin (Synonyms: KY 12420) |
| Catalog No.GC12338 |
Wortmannin is a highly potent direct inhibitor of PI3-kinase specificity originally derived from fungi.
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Cas No.: 19545-26-7
Sample solution is provided at 25 µL, 10mM.
Wortmannin is a highly potent direct inhibitor of PI3-kinase specificity originally derived from fungi (1,2). This inhibition is irreversible and non-competitive with an IC50 of 3 nM[2][3]. Wortmannin does not inhibit PI4 kinase, protein kinase C, or protein tyrosine kinases[4].
In Jurkat cell, at the concentrations of wortmannin commonly used to inhibit PI 3-kinases, PLK1 is also significantly inhibited[5]. In Swiss 3T3 cells, Wortmannin is a selective and reversible phosphatidylinositol 3-kinase inhibitor with an IC50 value of 1.9 nM[4].PI3-kinase is involved in the signal transduction pathway responsible for histamine secretion following stimulation of Fc epsilon RI and that wortmannin blocks these responses through direct interaction with the catalytic subunit of this enzyme[1].
Wortmannin treatment significantly slower the growth rate of murine C3H mammary tumor and human MCF-7 breast cancer xenograft. A dose of 1 mg/kg Wortmannin for 7 days decrease the tumor burdens in mice with established murine C3H mammary tumors by 54% relative to controls. Human MCF-7 breast cancer xenograft burdens are decreased by 97% relative to controls after 14 days of 1 mg/kg Wortmannin beginning 1 day after tumor implantation[6]. Wortmannin inhibits myosin light chain phosphorylation and contraction in rat aorta. As an inhibitor of MLCK, wortmannin can be used as a vasodilator and anti-inflammatory agent[7].
References:
[1]: Yano H, Nakanishi S, et,al. Inhibition of histamine secretion by wortmannin through the blockade of phosphatidylinositol 3-kinase in RBL-2H3 cells. J Biol Chem. 1993 Dec 5;268(34):25846-56. PMID: 7503989.
[2]: Moon EK, Kim SH, et,al. Autophagy inhibitors as a potential antiamoebic treatment for Acanthamoeba keratitis. Antimicrob Agents Chemother. 2015 Jul;59(7):4020-5. doi: 10.1128/AAC.05165-14. Epub 2015 Apr 20. PMID: 25896709; PMCID: PMC4468686.
[3]: Liu Y, Jiang N, et,al. Polo-like kinases inhibited by wortmannin. Labeling site and downstream effects. J Biol Chem. 2007 Jan 26;282(4):2505-11. doi: 10.1074/jbc.M609603200. Epub 2006 Nov 29. PMID: 17135248.
[4]: Powis G, Bonjouklian R, et,al. Wortmannin, a potent and selective inhibitor of phosphatidylinositol-3-kinase. Cancer Res. 1994 May 1;54(9):2419-23. PMID: 8162590.
[5]: Liu Y, Shreder KR, et,al. Wortmannin, a widely used phosphoinositide 3-kinase inhibitor, also potently inhibits mammalian polo-like kinase. Chem Biol. 2005 Jan;12(1):99-107. doi: 10.1016/j.chembiol.2004.11.009. PMID: 15664519.
[6]: Lemke LE, Paine-Murrieta GD, et,al. Wortmannin inhibits the growth of mammary tumors despite the existence of a novel wortmannin-insensitive phosphatidylinositol-3-kinase. Cancer Chemother Pharmacol. 1999;44(6):491-7. doi: 10.1007/s002800051123. PMID: 10550570.
[7]: Nakanishi S, Kakita S, et,al.Wortmannin, a microbial product inhibitor of myosin light chain kinase. J Biol Chem. 1992 Feb 5;267(4):2157-63. PMID: 1733924.
| Kinase experiment [1]: | |
Preparation Method | For studies of the kinetics of inhibition of PtdIns-3-kinase by wortmannin, bovine brain enzyme was incubated with 0 to 14 nM wortmannin with varying ATP concentrations from 2.5 to 20 μM. For studies of the time course of PtdIns-3-kinase inhibition, wortmannin 0 to 14 nM, enzyme, and PtdIns were incubated for various times at room temperature before adding [γ-32P]ATP to start the reaction. |
Reaction Conditions | 0-14 nM wortmannin |
Applications | Kinetic analysis demonstrates that wortmannin is a noncompetitive, irreversible inhibitor of phosphatidylinositol-3-kinase, with inactivation being both time- and concentration-dependent. |
| Cell experiment [2]: | |
Cell lines | Jurkat cells |
Preparation Method | Jurkat-soluble fractions were treated with AX7503 (50 nM) for 60 min with or without preincubation with various concentrations of wortmannin (0.25-50 nM) or LY294002 (10-50,000 nM) for 10 min. |
Reaction Conditions | Wortmannin (0.25-50 nM) for 10 min |
Applications | PLK1 activity was inhibited by wortmannin with an IC50 value of 24 nM. |
| Animal experiment [3]: | |
Animal models | Scid mice |
Preparation Method | Oral gavage; daily; in Scid mice; one group of eight mice is dosed with Wortmannin 1 mg/kg for all 14 days. The second group of eight mice is dosed with Wortmannin 1.5 mg/kg for the first 5 days and the dose is decreased to 1 mg/kg for the remaining treatment period. |
Dosage form | 1 mg/kg for 14 days; 1.5 mg/kg for 5 days + 1.0 mg/kg for 9 days. |
Applications | Wortmannin treatment significantly slower the growth rate of murine C3H mammary tumor and human MCF-7 breast cancer xenograft. A dose of 1 mg/kg Wortmannin for 7 days decrease the tumor burdens in mice with established murine C3H mammary tumors by 54% relative to controls. Human MCF-7 breast cancer xenograft burdens are decreased by 97% relative to controls after 14 days of 1 mg/kg Wortmannin beginning 1 day after tumor implantation. |
References: | |
| Cas No. | 19545-26-7 | SDF | |
| Synonyms | KY 12420 | ||
| Chemical Name | (1S,6bR,9aS,11R,11bR)-1-(methoxymethyl)-9a,11b-dimethyl-3,6,9-trioxo-3,6,6b,7,8,9,9a,10,11,11b-decahydro-1H-furo[4,3,2-de]indeno[4,5-h]isochromen-11-yl acetate | ||
| Canonical SMILES | O=C1[C@](C([H])([H])[C@@]2([H])OC(C([H])([H])[H])=O)(C([H])([H])[H])[C@](C([H])([H])C1([H])[H])([H])C(C3=O)=C2[C@]4(C([H])([H])[H])C5=C3OC([H])=C5C(O[C@]4([H])C([H])([H])OC([H])([H])[H])=O | ||
| Formula | C23H24O8 | M.Wt | 428.43 |
| Solubility | ≥ 21.42mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.3341 mL | 11.6705 mL | 23.341 mL |
| 5 mM | 0.4668 mL | 2.3341 mL | 4.6682 mL |
| 10 mM | 0.2334 mL | 1.1671 mL | 2.3341 mL |
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- Purity: >99.50%
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Related Biological Data
Megakaryopoiesis of CD34+CD90+ HSCs also required the activation of the PI3K- HSCB signaling axis. (E) Western blotting analyses demonstrated that both knocking down HSCB and wortmannin treatment could increase the protein level of TACC3 while reduce FOG1 nuclear translocation.
After the FBS deprivation treatment, K562 cells were incubated for 48 hours with 300 nM ruxolitinib, 200 nM wortmannin (GlpBio), 2 μM lonafarnib dissolved in dimethylsulfoxide (DMSO) and 10 μM MG132 dissolved.
Elife 13 (2024): RP95815. PMID: 38757931 -
Related Biological Data
Isolation and evaluation of properties of M2-EVs in vitro.(E)Representative images of M2-EVs uptake in PMφ stained with FITC Phalloidin(Green) and DAPI(Blue).Cells were pre-treated with DMSO, Baf-A1, Cyto D or Wtmn(Wortmannin) for 15 min,and the incubated PKH26-labeled M2-EVs (Red) for 4 h.
To determine the cellular uptake mechanism of M2-EVs,cells were pretreated with inhibitors including Bafilomycin A1(10nM),Cytochalasin D(0.5μM),and Wortmannin(0.5μM,Glpbio) for 30 min,and then incubated with PKH26-labeled EVs.
J Control Release 349 (2022): 118-132. PMID: 35792186
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