XL-888 (Synonyms: Xl 888, Xl888) |
| カタログ番号GC16892 |
口内で利用可能なHsp90阻害剤
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1149705-71-4
Sample solution is provided at 25 µL, 10mM.
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XL-888 is a novel and orally-bioavailable inhibitor of heat shock protein 90 (HSP90) that selectively inhibits HSP90α and HSP90β with values of 50% inhibition concentration IC50 of 22 nM and 44 nM respectively. It also exerts considerably weaker inhibition against a range of other diverse kinases with IC50 more than 3600 nM for all. X-ray crystallographic analysis reveals that the XL-888 binds to HSP90 through the formation of H-bonding between the N-(R)-sec-butylanthranilamide moiety of XL-888 and ASP93 of HSP90. In recent studies, XL-888 has exhibits strong anti-proliferative activities in a panel of tumor cells with values of IC50 ranging from 0.1 nM to 45.5 nM.
Reference
[1].Paraiso KH, Haarberg HE, Wood E, Rebecca VW, Chen YA, Xiang Y, Ribas A, Lo RS, Weber JS, Sondak VK, John JK, Sarnaik AA, Koomen JM, Smalley KS. The HSP90 inhibitor XL888 overcomes BRAF inhibitor resistance mediated through diverse mechanisms. Clin Cancer Res. 2012; 18(9):2502-2514
[2].Bussenius J, Blazey CM, Aay N, Anand NK, Arcalas A, Baik T, Bowles OJ, Buhr CA, Costanzo S, Curtis JK, DeFina SC, Dubenko L, Heuer TS, Huang P, Jaeger C, Joshi A, Kennedy AR, Kim AI, Lara K, Lee J, Li J, Lougheed JC, Ma S, Malek S, Manalo JC, Martini JF, McGrath G, Nicoll M, Nuss JM, Pack M, Peto CJ, Tsang TH, Wang L, Womble SW, Yakes M, Zhang W, Rice KD. Discovery of XL888: a novel tropane-derived small molecule inhibitor of HSP90. Bioorg Med Chem Lett. 2012; 22(17): 5396-5404.
| Cell experiment [1]: | |
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Cell lines |
Vemurafenib-resistant melanoma cell lines |
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Preparation method |
The solubility of this compound in DMSO is > 10 mM. 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. |
|
Reaction Conditions |
300 nM; 72 or 144 hrs |
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Applications |
In Vemurafenib-resistant melanoma cell lines, XL888 (300 nM) induced high levels (> 66%) of apoptosis and loss of mitochondrial membrane potential. |
| Animal experiment [1]: | |
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Animal models |
Mice bearing M229R xenografts |
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Dosage form |
100 mg/kg; p.o.; 3 times per week, for 15 days |
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Applications |
XL888 (100 mg/kg) significantly induced the regression of established M229R xenografts in SCID mice. |
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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]. Paraiso KH, Haarberg HE, Wood E, Rebecca VW, Chen YA, Xiang Y, Ribas A, Lo RS, Weber JS, Sondak VK, John JK, Sarnaik AA, Koomen JM, Smalley KS. The HSP90 inhibitor XL888 overcomes BRAF inhibitor resistance mediated through diverse mechanisms. Clin Cancer Res. 2012; 18(9):2502-2514. | |
| Cas No. | 1149705-71-4 | SDF | |
| 同義語 | Xl 888, Xl888 | ||
| Chemical Name | 2-(butan-2-ylamino)-4-N-[(1R,5S)-8-[5-(cyclopropanecarbonyl)pyridin-2-yl]-8-azabicyclo[3.2.1]octan-3-yl]-5-methylbenzene-1,4-dicarboxamide | ||
| Canonical SMILES | CCC(C)NC1=CC(=C(C=C1C(=O)N)C)C(=O)NC2CC3CCC(C2)N3C4=NC=C(C=C4)C(=O)C5CC5 | ||
| Formula | C29H37N5O3 | M.Wt | 503.64 |
| 溶解度 | ≥ 18.2mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9855 mL | 9.9277 mL | 19.8555 mL |
| 5 mM | 397.1 μL | 1.9855 mL | 3.9711 mL |
| 10 mM | 198.6 μL | 992.8 μL | 1.9855 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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