产品说明书

XL388

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Chemical Structure| 1251156-08-7 同义名 : -
CAS号 : 1251156-08-7
货号 : A210267
分子式 : C23H22FN3O4S
纯度 : 99%+
分子量 : 455.502
MDL号 : MFCD24386875
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(109.77 mM)，配合低频超声助溶，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：

30% PEG400+0.5% Tween80+5% propylene glycol+water 30 mg/mL suspension

生物活性
靶点

  • mTORC1

    mTORC1, IC50:8 nM

  • mTORC2

    mTORC2, IC50:166 nM

  • mTOR

    mTOR, IC50:9.9 nM
描述 The mammalian target of rapamycin (mTOR) is a large protein kinase that integrates both extracellular and intracellular signals of cellular growth, proliferation, and survival, which lies in two different multi-protein complexes, including mTOR complex 1(mTORC1) and mTORC2. XL388 is an orally bioavailable inhibitor of the mTOR that inhibits cellular phosphorylation of mTOR complex 1 (p-p70S6K, pS6, and p-4E-BP1) and mTOR complex 2 (pAKT (S473)) substrates, with IC50 value of 9.9 nM[4]. XL388(5-200nM)-treated MG-63 cells showed increased percentage of G1 phase and decreased S phase and G2-M phase compared with untreated cells. Oral administration of XL388 (20 mg/kg body weight, every three days, × 7 times) significantly inhibited human osteosarcoma cell line U2OS xenograft growth in severe combined immuno-defcient mice more than 40%[5]. XL388 (10-1000 nM, 24-96 h) dose- and time-dependently induced renal cell carcinoma cell line 786-0 cell death. Consistently, oral administration of XL388 (20 mg/kg, every three days, × 7 times) dramatically inhibited 786-0 tumor growth in nude mice more than 60%[6].
作用机制 XL388 inhibits mTOR activity in an ATP-competitive manner.
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.20mL

0.44mL

0.22mL

10.98mL

2.20mL

1.10mL

21.95mL

4.39mL

2.20mL
参考文献

[1]Takeuchi CS, Kim BG, et al. Discovery of a novel class of highly potent, selective, ATP-competitive, and orally bioavailable inhibitors of the mammalian target of rapamycin (mTOR). J Med Chem. 2013 Mar 28;56(6):2218-34.

[2]Zhu YR, Zhou XZ, et al. The anti-cancer activity of the mTORC1/2 dual inhibitor XL388 in preclinical osteosarcoma models. Oncotarget. 2016 Aug 2;7(31):49527-49538.

[3]Yu K, Toral-Barza L, et al. Biochemical, cellular, and in vivo activity of novel ATP-competitive and selective inhibitors of the mammalian target of rapamycin. Cancer Res. 2009 Aug 1;69(15):6232-40.

[4]Takeuchi CS, Kim BG, Blazey CM, Ma S, Johnson HW, Anand NK, Arcalas A, Baik TG, Buhr CA, Cannoy J, Epshteyn S, Joshi A, Lara K, Lee MS, Wang L, Leahy JW, Nuss JM, Aay N, Aoyama R, Foster P, Lee J, Lehoux I, Munagala N, Plonowski A, Rajan S, Woolfrey J, Yamaguchi K, Lamb P, Miller N. Discovery of a novel class of highly potent, selective, ATP-competitive, and orally bioavailable inhibitors of the mammalian target of rapamycin (mTOR). J Med Chem. 2013 Mar 28;56(6):2218-34. doi: 10.1021/jm3007933. Epub 2013 Mar 7. PMID: 23394126.

[5]Zhu YR, Zhou XZ, Zhu LQ, Yao C, Fang JF, Zhou F, Deng XW, Zhang YQ. The anti-cancer activity of the mTORC1/2 dual inhibitor XL388 in preclinical osteosarcoma models. Oncotarget. 2016 Aug 2;7(31):49527-49538. doi: 10.18632/oncotarget.10389. PMID: 27385099; PMCID: PMC5226526.

[6]Xiong Z, Zang Y, Zhong S, Zou L, Wu Y, Liu S, Fang Z, Shen Z, Ding Q, Chen S. The preclinical assessment of XL388, a mTOR kinase inhibitor, as a promising anti-renal cell carcinoma agent. Oncotarget. 2017 May 2;8(18):30151-30161. doi: 10.18632/oncotarget.15620. PMID: 28404914; PMCID: PMC5444733.