Wortmannin
Wortmannin is a selective and irreversible inhibitor of phosphatidylinositol-3-kinase with IC50 value of 1.9nM [1].
Wortmannin is a microbial product. It is produced by a fungal strain, Talaromyces wortmannin KY12420 and is screened out as a potent inhibitor of myosin light chain kina (MLCK). Wortmannin inhibits MLCK as directly interacting with the catalytic domain but not the calmodulin or the regulatory domains. It is found to be a non-competitive inhibitor. The IC50 value of wortmannin for MLCK is 1.9μM. Wortmannin inhibits the phosphorylation and contraction of myosin light chain in rat aort. As an inhibitor of MLCK, wortmannin is developed as vasodilators and anti-inflammatory agent [2].
Wortmannin is also found to be an inhibitor of PI3K with IC50 of 1.9nM in antiphosphotyrosine immunoprecipitates from Swiss 3T3 cells. The inhibition mode is noncompetitive with respect to ATP. Wortmannin is a highly selective inhibitor of PI3K. It has no inhibition effect on Ptdlns-4-kinase, protein kinase C, c-src protein tyrosine kinase and phosphoinositide-specific phospholipase C [1].
References:
[1] Powis G, Bonjouklian R, Berggren M M, et al. Wortmannin, a potent and selective inhibitor of phosphatidylinositol-3-kinase. Cancer Research, 1994, 54(9): 2419-2423.
[2] Nakanishi S, Kakita S, Takahashi I, et al. Wortmannin, a microbial product inhibitor of myosin light chain kinase. Journal of Biological Chemistry, 1992, 267(4): 2157-2163.
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| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 428.43 |
| Cas No. | 19545-26-7 |
| Formula | C23H24O8 |
| Solubility | ≥21.42 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH |
| 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 |
| SDF | Download SDF |
| 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 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
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Cell lines |
v-sis NIH 3T3 cells |
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Preparation method |
The solubility of this compound in DMSO is >21.4 mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37°C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below - 20°C for several months. |
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Reacting condition |
1.3 μM |
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Applications |
In PDGF-stimulated v-sis NIH 3T3 cells, Wortmannin almost completely inhibited the formation of Ptdlns-3-phosphates. However, in resting cells, Wortmannin showed no effect on the pattern of phospholipids. |
| Animal experiment [2]: | |
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Animal models |
Immunodeficient mice bearing orthotopic human pancreatic cancer xenografts |
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Dosage form |
0-0.7 mg/kg; i.v.; 0-4 hrs |
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Applications |
In orthotopic human pancreatic cancer xenografts, PKB/Akt phosphorylation was inhibited by Wortmannin in a time- and dose-dependent manner, and reached a plateau at 4 hrs and at 0.7 mg/kg. Meanwhile, the levels of PKB/Akt phosphorylation were decreased maximally by ~50%. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Powis G, Bonjouklian R, Berggren M M, et al. Wortmannin, a potent and selective inhibitor of phosphatidylinositol-3-kinase. Cancer Research, 1994, 54(9): 2419-2423. [2]. Ng SS, Tsao MS, Nicklee T, Hedley DW. Wortmannin inhibits pkb/akt phosphorylation and promotes gemcitabine antitumor activity in orthotopic human pancreatic cancer xenografts in immunodeficient mice. Clin Cancer Res. 2001 Oct;7(10):3269-75. |
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| Description | Wortmannin is an inhibitor of PI3K with an IC50 value of 3 nM. | |||||
| Targets | PI3K | DNA-PK | ATM | MLCK | ATR | |
| IC50 | 3 nM | 16 nM | 150 nM | 170 nM | 1.8 μM | |
Quality Control & MSDS
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