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Chemical Structure| 1251156-08-7 Chemical Structure| 1251156-08-7

Structure of XL388
CAS No.: 1251156-08-7

Chemical Structure| 1251156-08-7

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XL388 is a potent and selective ATP-competitive mTOR inhibitor with IC50 value of 9.9 nM.

4.5 *For Research Use Only !

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Product Details of XL388

CAS No. :1251156-08-7
Formula : C23H22FN3O4S
M.W : 455.50
SMILES Code : O=C(N1CCOC2=CC=C(C3=CC=C(N)N=C3)C=C2C1)C4=CC=C(S(=O)(C)=O)C(F)=C4C
MDL No. :MFCD24386875
InChI Key :LNFBAYSBVQBKFR-UHFFFAOYSA-N
Pubchem ID :59604787

Safety of XL388

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319-H335
Precautionary Statements:P280-P304+P340+P312-P305+P351+P338-P337+P313

Related Pathways of XL388

PI3K-AKT

Isoform Comparison

Biological Activity

Target
  • mTORC1

    mTORC1, IC50:8 nM

  • mTORC2

    mTORC2, IC50:166 nM

  • mTOR

    mTOR, IC50:9.9 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
LN-18 cells 300 and 1000 nM 24 hours XL388 modestly suppressed cell growth only at the higher dose of 1,000 nM. Int J Oncol. 2021 Oct;59(4):83
LN-18 cells 100, 500, 1000, 1500, 2000 nM 24 hours XL388 completely inhibited phosphorylation of PRAS40 only at higher doses of 1,500 and 2,000 nM, a modest suppression was observed at 1,000 nM, and no changes in the levels of PRAS40 phosphorylation was noted at 100 and 500 nM. Int J Oncol. 2021 Oct;59(4):83
LN-18 cells 50, 300 and 1000 nM 3 days Treatment with XL388 failed to suppress GB cell migration at all doses as compared to the controls. Int J Oncol. 2021 Oct;59(4):83
LN-18 cells 500 nM 4 hours XL388 resulted in the least suppression of S‑phase entry, showing 12% of total cells in S‑phase. Int J Oncol. 2021 Oct;59(4):83

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Sprague-Dawley rats Nerve injury-induced chronic pain model External carotid artery injection 500 nM Single administration To observe the effects of mTOR inhibition on brain activity in chronic pain rats, results showed that XL388 significantly reduced signal intensity in pain-related brain regions. Mol Brain. 2020 Nov 23;13(1):158

Protocol

Bio Calculators
Preparing Stock Solutions 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

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

[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.

 

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