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Wortmannin

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Chemical Structure| 19545-26-7 同义名 : SL-2052;KY 12420;NSC 627609;BRN 0067676
CAS号 : 19545-26-7
货号 : A117244
分子式 : C23H24O8
纯度 : 99%+
分子量 : 428.432
MDL号 : MFCD00133927
存储条件：

粉末 Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(116.7 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

5% DMSO+40% PEG 300+5% Tween 80+water 5 mg/mL

生物活性
靶点

  • PI3K

    PI3K, IC50:3 nM

  • ATM

    ATM, IC50:150 nM
描述 Phosphoinositide-3-kinase family (PI3Ks) phosphorylates PtdIns (Phosphatidylinositol), PtdIns4P (Phosphatidylinositol 4-phosphate) and PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role in recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. KY-12420, also termed wortmannin, is a PI3K inhibitor. The IC50 value of KY-12420 against PI3K was 3 nM according to purified calf PI3K assay or cell based immunoprecipitate assay. In intact cells, KY-12420 inhibited PI3K activity with an IC50 of 2 nM[3]. Post 24 h incubation, KY-12420 could sensitize melanoma cell lines A375, Mel-HO, as well as respective TRAIL resistant cell lines, for TRAIL-induced apoptosis at the concentrations of 4 μM or 8 μM, as revealed by a sub-G1 cell analysis, while KY-12420 alone was not effective[4]. In lung cancer cell lines A549 and H1703, KY-12420 at the concentration of 2.5 μM also enhanced cytotoxicity induced by tamoxifen[5]. In an orthotopic pancreatic tumor model established by injection of PK1 cells into the pancreas of SCID mice, KY-12420 plus gemcitabine was administrated via i.p. injection. The dose of KY-12420 was 0.35 mg/kg and the dose of gemcitabine was 80 mg/kg. Both of the agents were injected biweekly for a total treatment period of 5 weeks. The result turned out that KY-12420 plus gemcitabine reduced tumor weights by 5-fold relative to the vehicle control. For comparison, the group of gemcitabine alone at the same dose and schedule reduced tumor weights by 1.4-fold, and the group of KY-12420 alone failed to inhibit tumor growth[6].
作用机制 Based on the X-ray crystallographic structure of KY-12420 bound to PI3Kγ in the kinase’s ATP binding pocket, KY-12420 most closely fits and fills the active site and induces a conformational change in the catalytic domain of the kinase[7].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
5637 10 μM Apoptosis Assay 40 min reverses p21WAF1 expression, CDK expression, and cell inhibition induced by fucoidan 24333868
A-375 4/8 μM Apoptosis Assay 24 h enhances TRAIL-induced apoptosis  24113173
A-375-TS 4/8 μM Apoptosis Assay 24 h enhances TRAIL-induced apoptosis  24113173
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.33mL

0.47mL

0.23mL

11.67mL

2.33mL

1.17mL

23.34mL

4.67mL

2.33mL
参考文献

[1]Carter AN, Born HA, et al. Wortmannin Attenuates Seizure-Induced Hyperactive PI3K/Akt/mTOR Signaling, Impaired Memory, and Spine Dysmorphology in Rats. eNeuro. 2017 Jun 12;4(3). pii: ENEURO.0354-16.2017. .

[2]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.

[3]Yano H, Nakanishi S, Kimura K, Hanai N, Saitoh Y, Fukui Y, Nonomura Y, Matsuda Y. 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.

[4]Quast SA, Berger A, Eberle J. ROS-dependent phosphorylation of Bax by wortmannin sensitizes melanoma cells for TRAIL-induced apoptosis. Cell Death Dis. 2013 Oct 10;4(10):e839.

[5]Ko JC, Chiu HC, Syu JJ, Chen CY, Jian YT, Huang YJ, Wo TY, Jian YJ, Chang PY, Wang TJ, Lin YW. Down-regulation of MSH2 expression by Hsp90 inhibition enhances cytotoxicity affected by tamoxifen in human lung cancer cells. Biochem Biophys Res Commun. 2015 Jan 2;456(1):506-12.

[6]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.

[7]Walker EH, Pacold ME, Perisic O, Stephens L, Hawkins PT, Wymann MP, Williams RL. Structural determinants of phosphoinositide 3-kinase inhibition by wortmannin, LY294002, quercetin, myricetin, and staurosporine. Mol Cell. 2000 Oct;6(4):909-19.