XL388MTOR inhibitor,highly potent and selective CAS# 1251156-08-7 |
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Quality Control & MSDS
Number of papers citing our products
Chemical structure
3D structure
| Cas No. | 1251156-08-7 | SDF | Download SDF |
| PubChem ID | 59604787 | Appearance | Powder |
| Formula | C23H22FN3O4S | M.Wt | 455.5 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : 50 mg/mL (109.77 mM; Need ultrasonic) | ||
| Chemical Name | [7-(6-aminopyridin-3-yl)-3,5-dihydro-2H-1,4-benzoxazepin-4-yl]-(3-fluoro-2-methyl-4-methylsulfonylphenyl)methanone | ||
| SMILES | CC1=C(C=CC(=C1F)S(=O)(=O)C)C(=O)N2CCOC3=C(C2)C=C(C=C3)C4=CN=C(C=C4)N | ||
| Standard InChIKey | LNFBAYSBVQBKFR-UHFFFAOYSA-N | ||
| Standard InChI | InChI=1S/C23H22FN3O4S/c1-14-18(5-7-20(22(14)24)32(2,29)30)23(28)27-9-10-31-19-6-3-15(11-17(19)13-27)16-4-8-21(25)26-12-16/h3-8,11-12H,9-10,13H2,1-2H3,(H2,25,26) | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | Potent and selective mTOR inhibitor (IC50 = 9.9 nM). Inhibits mTOR activity in an ATP-competitive manner. Exhibits >300-fold selectivity for mTOR over PI 3-K and a range of other kinases. Displays antitumor activity in athymic nude mice implanted with tumor xenografts. |
XL388 Dilution Calculator
XL388 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 2.1954 mL | 10.9769 mL | 21.9539 mL | 43.9078 mL | 54.8847 mL |
| 5 mM | 0.4391 mL | 2.1954 mL | 4.3908 mL | 8.7816 mL | 10.9769 mL |
| 10 mM | 0.2195 mL | 1.0977 mL | 2.1954 mL | 4.3908 mL | 5.4885 mL |
| 50 mM | 0.0439 mL | 0.2195 mL | 0.4391 mL | 0.8782 mL | 1.0977 mL |
| 100 mM | 0.022 mL | 0.1098 mL | 0.2195 mL | 0.4391 mL | 0.5488 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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XL388 is a selective inhibitor of mTOR with IC50 value of 9.9 nM [1].
mTOR, a member of the phosphatidylinositol 3-kinase (PI3K) cell survival pathway, plays an important role in the regulation of cell growth and proliferation by monitoring nutrient availability, cellular energy levels, oxygen levels, and mitogenic signals [1].
In MCF-7 cells, XL388 blocks mTORC1 phosphorylation of p70S6K with an IC50 value of 94 nM and mTORC2 phosphorylation of AKT with an IC50 value of 350 nM. When assayed alone, XL388 inhibits the viability of hematopoietic tumor cell lines in vitro. Also, XL388 synergizes with chemotherapeutics in cell-based assays to block cell viability [1].
XL388 shows robust antitumor activity in multiple xenograft models when dosed orally once daily in mice, especially in the MCF-7 xenograft model it shows > 100% tumor growth inhibition [1]. XL388 displays strong pharmacokinetics and good oral exposure in multiple species. Oral administration of XL388 to athymic nude mice implanted with MCF-7 xenograft tumors afforded significant and dose-dependent antitumor activity, which suggest that block of mTOR signaling is a viable target for antitumor activity [2].
References:
[1]. Nicole Miller. Abstract B146: XL388: A novel, selective, orally bioavailable mTORC1 and mTORC2 inhibitor that demonstrates pharmacodynamic and antitumor activity in multiple human cancer xenograft models. Mol Cancer Ther, 2009, 8(12 Suppl):B146.
[2].Takeuchi CS, Kim BG, Blazey CM, 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, 56(6):2218-34.
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The anti-cancer activity of the mTORC1/2 dual inhibitor XL388 in preclinical osteosarcoma models.[Pubmed:27385099]
Oncotarget. 2016 Aug 2;7(31):49527-49538.
In the present study, we investigated the activity of XL388, a novel mammalian target of rapamycin (mTOR) complex 1/2 (mTORC1/2) dual inhibitor, in preclinical osteosarcoma (OS) models. XL388 was cytotoxic, cytostatic and pro-apoptotic to multiple established OS cell lines and primary human OS cells. XL388 blocked mTORC1/2 activation and downregulated cyclin D1/B1 expressions in OS cells, leaving AKT Thr-308 phosphorylation un-affected. Intriguingly, AKT1 T308A mutation potentiated XL388-induced cytotoxicity in OS cells. XL388 activated cytoprotective autophagy in OS cells. Autophagy inhibition, either pharmacologically or genetically, augmented XL388-induced anti-OS activity. Further, XL388 oral administration inhibited U2OS xenografts growth in severe combined immuno-deficient (SCID) mice. Such activity was enhanced with co-administration of the autophagy inhibitor 3-methyladenine (3-MA). Similarly, Beclin-1-silenced U2OS xenografts were remarkably more sensitive to XL388. Thus, concurrent blockage of mTORC1/2 with XL388 may have therapeutic value for OS.
Discovery of a novel class of highly potent, selective, ATP-competitive, and orally bioavailable inhibitors of the mammalian target of rapamycin (mTOR).[Pubmed:23394126]
J Med Chem. 2013 Mar 28;56(6):2218-34.
A series of novel, highly potent, selective, and ATP-competitive mammalian target of rapamycin (mTOR) inhibitors based on a benzoxazepine scaffold have been identified. Lead optimization resulted in the discovery of inhibitors with low nanomolar activity and greater than 1000-fold selectivity over the closely related PI3K kinases. Compound 28 (XL388) inhibited cellular phosphorylation of mTOR complex 1 (p-p70S6K, pS6, and p-4E-BP1) and mTOR complex 2 (pAKT (S473)) substrates. Furthermore, this compound displayed good pharmacokinetics and oral exposure in multiple species with moderate bioavailability. Oral administration of compound 28 to athymic nude mice implanted with human tumor xenografts afforded significant and dose-dependent antitumor activity.
