Wortmannin (Synonyms: KY 12420) |
Catalog No.GC12338
One-Click Copy Product Info
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Wortmannin is a potent, selective, and irreversible PI3K inhibitor with an IC50 value of 4.2nM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 19545-26-7
Sample solution is provided at 25 µL, 10mM.
Wortmannin is a potent, selective, and irreversible PI3K inhibitor with an IC50 value of 4.2nM[1]. Wortmannin is an effective radiosensitizer that irreversibly inhibits DNA-dependent protein kinase (DNA-PK) and ataxia telangiectasia mutated (ATM) with IC50 values of 16nM and 150nM, respectively[2]. By inhibiting the activity of PI3K, Wortmannin regulates the expression of survivin, cyclinD1, PI3K and p-Akt, and reduces cell migration activity and induces the expression of E-cadherin[3]. Wortmannin has been widely used to inhibit the secretion of histamine in cells[4].
In vitro, Wortmannin treatment for 24 hours significantly inhibited the growth of K562 cells, with an IC50 value of 25nM[5]. Treatment with 2µM Wortmannin for 24 hours significantly induced apoptosis in MCF-7 cells, accompanied by chromatin condensation, nuclear fragmentation, reactive oxygen species, and membrane blebbing[6]. Treatment of MDA-MB-231 cells with 200nM Wortmannin for 4 hours significantly inhibited the upregulation of Akt phosphorylation, NF-κB, MMP-9, and IL-8[7].
In vivo, Wortmannin treatment via oral administration at a dose of 1.5mg/kg/day for 22 days reduced insulin signaling and mortality in seizure-prone Pcmt1−/− mice[8]. Daily intraperitoneal injection of Wortmannin at a dose of 1mg/kg/day for 28 days significantly inhibited tumor growth in the Colo-699 xenograft mouse model and prolonged the survival time of the mice[9].
References:
[1] Walker E H, Pacold M E, Perisic O, et al. Structural determinants of phosphoinositide 3-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine[J]. Molecular cell, 2000, 6(4): 909-919.
[2] Sarkaria J N, Tibbetts R S, Busby E C, et al. Inhibition of phosphoinositide 3-kinase related kinases by the radiosensitizing agent wortmannin[J]. Cancer research, 1998, 58(19): 4375-4382.
[3] Bani N, Rahmani F, Shakour N, et al. Wortmannin inhibits cell growth and induces apoptosis in colorectal cancer cells by suppressing the PI3K/AKT pathway[J]. Anti-Cancer Agents in Medicinal Chemistry-Anti-Cancer Agents), 2024, 24(12): 916-927.
[4] Yano H, Nakanishi S, Kimura K, et al. Inhibition of histamine secretion by wortmannin through the blockade of phosphatidylinositol 3-kinase in RBL-2H3 cells[J]. Journal of Biological Chemistry, 1993, 268(34): 25846-25856.
[5] Wu Q, Chen Y, Cui G, et al. Wortmannin inhibits K562 lukemic cells by regulating PI3k/Akt channel in vitro[J]. Journal of Huazhong University of Science and Technology [Medical Sciences], 2009, 29(4): 451-456.
[6] Akter R, Hossain M Z, Kleve M G, et al. Wortmannin induces MCF-7 breast cancer cell death via the apoptotic pathway, involving chromatin condensation, generation of reactive oxygen species, and membrane blebbing[J]. Breast Cancer: Targets and Therapy, 2012: 103-113.
[7] Li J, Li F, Wang H, et al. Wortmannin reduces metastasis and angiogenesis of human breast cancer cells via nuclear factor-κB-dependent matrix metalloproteinase-9 and interleukin-8 pathways[J]. Journal of International Medical Research, 2012, 40(3): 867-876.
[8] MacKay K B, Lowenson J D, Clarke S G. Wortmannin reduces insulin signaling and death in seizure-prone Pcmt1−/− mice[J]. 2012.
[9] Boehle A, Kurdow R, Boenicke L, et al. Wortmannin inhibits growth of human non-small-cell lung cancer in vitro and in vivo[J]. Langenbeck's archives of surgery, 2002, 387(5): 234-239.
| Cell experiment [1]: | |
Cell lines | K562 cells |
Preparation Method | K562 cells were cultured in RPMI-1640 medium supplemented with 10% fetal bovine serum, 100U/ml penicillin, and 100μg/ml streptomycin at 37°C with 5% CO2 and 95% saturated atmospheric humidity. Cells were seeded into 96-well microplates at a density of 5×105 cells/ml for 24h. Various concentrations of Wortmannin (0, 6.25, 12.5, 25, 50, and 100nM) were added to each well. After 24h of incubation, cell viability was analyzed. |
Reaction Conditions | 0, 6.25, 12.5, 25, 50, and 100nM; 24h |
Applications | Wortmannin treatment significantly reduced the cell viability of K562 cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | Female SCID-bg mice |
Preparation Method | Female SCID-bg mice (6 weeks old; 18-20g) were housed under standard laboratory conditions on a 12-hour light/dark cycle (lights on at 7:00 am), constant temperature (23±2°C), and constant humidity (60±5%), ad libitum food and water. For induction of intrapulmonary tumor growth, mice were anesthetized by intraperitoneal injection of 240mg/kg Avertin, and 2×106 Colo-699 cells were introduced below the visceral pleura. Daily intraperitoneal injection of Wortmannin at a dose of 1mg/kg for 28 days was performed, after which the tumor volume was analyzed in mice. |
Dosage form | 1mg/kg/day; 28 days; i.p. |
Applications | Wortmannin treatment inhibited tumor growth in the Colo-699 xenograft mouse models. |
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. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.3341 mL | 11.6705 mL | 23.341 mL |
| 5 mM | 466.8 μL | 2.3341 mL | 4.6682 mL |
| 10 mM | 233.4 μL | 1.1671 mL | 2.3341 mL |
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
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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
Average Rating: 5 (Based on Reviews and 29 reference(s) in Google Scholar.)