LY335979 (Zosuquidar 3HCL) (Synonyms: RS 33295-198; Zosuquidar trihydrochloride; LY335979; LY-335979) |
| رقم الكتالوجGC16609 |
Zosuquidar (LY335979) ثلاثي هيدروكلوريد هو مثبط P-glycoprotein (P-gp) (Ki = 59 نانومتر). يُظهر LY335979 (Zosuquidar 3HCL) أنشطة مضادة للأورام ، ويمكن استخدامه في أبحاث ابيضاض الدم النقوي الحاد (AML).
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 167465-36-3
Sample solution is provided at 25 µL, 10mM.
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LY335979 is a selective inhibitor of P-Gp with IC50 value of 1.2 nM [1, 2].
P-gp (P-glycoprotein) is a member of ATP-binding cassette (ABC) transporters and plays a pivotal role in pumping many foreign substances out of cells. It has been reported that abnormal expression of P-Gp is correlated with the multidrug resistance of tumor cells [3].
LY335979 is a potent P-Gp inhibitor and has a different selectivity with the reported P-Gp inhibitor cyclosporin A or verapamil. In drug-resistant cell line HL60/VCR with highly expression of P-Gp, LY335979 exhibited highly restore ability of P-Gp than cyclosporin A or verapamil and the IC 50 value of 1.2 nM [1]. When tested with a panel of cell lines over-expressed P-Gp (CEM/VLB100, MCF-7/ADR, 2780AD, P388/ADR, and UCLA-P3.003VLB), administration of LY335979 reversed the cells resistance to Vinblastine, Doxorubicin, Btoposide and Taxol by inhibiting P-Gp activity [2].
In female nude mice model with UCLA-P3.003VLB MDR tumor cells subcutaneous xenograft, pre-treated with LY335979 (30mg/kg) restored tumor cells sensitivity to Taxol (20 mg/kg) which combination markedly suppressed solid tumor growth compared with control group [2].
References:
1. Green, L.J., P. Marder, and C.A. Slapak, Modulation by LY335979 of P-glycoprotein function in multidrug-resistant cell lines and human natural killer cells. Biochem Pharmacol, 2001. 61(11): p. 1393-9.
2. Dantzig, A.H., et al., Reversal of P-glycoprotein-mediated multidrug resistance by a potent cyclopropyldibenzosuberane modulator, LY335979. Cancer Res, 1996. 56(18): p. 4171-9.
3. Hu, T., et al., Reversal of P-glycoprotein (P-gp) mediated multidrug resistance in colon cancer cells by cryptotanshinone and dihydrotanshinone of Salvia miltiorrhiza. Phytomedicine, 2014. 21(11): p. 1264-72.
| Kinase experiment [1]: | |
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ATPase assay |
P-Glycoprotein ATPase activity was measured by the liberation of inorganic phosphate from ATP. The assay was measured in a 96-well plate for 90 mins at 37 °C. Membranes (8 ~ 10 μg protein) were incubated in a total volume of 100 μL of buffer A containing 5 mM sodium azide, 1 mM ouabain, 1 mM EGTA, 3 mM ATP, an ATP regenerating system composed of 5 mM phosphoenolpyruvate, and 3.6 units/mL pyruvate kinase in the presence and absence of 1 mM sodium vanadate. Pgp-ATPase activity was defined as the vanadate-sensitive portion of the total ATPase activity. Plates were read 3 mins after the addition of the detection solution. The absorbance was measured at 690 nm by a microtiter dish reader. A phosphate standard curve was used to calculate the μmol of phosphate formed. Samples were measured in triplicate. |
| Cell experiment [1]: | |
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Cell lines |
CEM/VLB100, MCF-7/ADR, 2780AD, P388/ADR and UCLA-P3.003VLB cells |
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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. |
|
Reacting condition |
0.1 ~ 2 μM |
|
Applications |
LY335979 was an effective modulator, with maximal activity in reversing the sensitivity of resistant cells to the various anticancer drugs (Vinblastine, Doxorubicin, Btoposide and Taxol) at the concentrations of 0.1 ~ 2 μM. At the concentration of 0.05 μM, the modulator activity of LY335979 was diminished by about 50%. |
| Animal experiment [1]: | |
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Animal models |
Nude mice bearing UCLA-P3.003VLB tumor cells |
|
Dosage form |
30 mg/kg; i.p. |
|
Applications |
In a Pgp-expressing human non-small cell lung carcinoma xenograft model, the combination therapy of 20 mg/kg Taxol and 30 mg/kg LY335979 significantly suppressed solid tumor growth at days 12 and 19. In addition, no increased weight loss was observed. |
|
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. |
|
References: [1]. Dantzig, A.H., et al., Reversal of P-glycoprotein-mediated multidrug resistance by a potent cyclopropyldibenzosuberane modulator, LY335979. Cancer Res, 1996. 56(18): p. 4171-9. | |
| Cas No. | 167465-36-3 | SDF | |
| المرادفات | RS 33295-198; Zosuquidar trihydrochloride; LY335979; LY-335979 | ||
| Chemical Name | (R)-1-(4-((1aR,6s,10bS)-1,1-difluoro-1,1a,6,10b-tetrahydrodibenzo[a,e]cyclopropa[c][7]annulen-6-yl)piperazin-1-yl)-3-(quinolin-5-yloxy)propan-2-ol trihydrochloride | ||
| Canonical SMILES | FC1([C@H](C2=CC=CC=C23)[C@@H]1C4=CC=CC=C4[C@H]3N5CCN(C[C@H](COC6=C7C(N=CC=C7)=CC=C6)O)CC5)F.Cl.Cl.Cl | ||
| Formula | C32H34Cl3F2N3O2 | M.Wt | 637 |
| الذوبان | ≥ 17.1mg/mL in DMSO | Storage | Store at -20°C,unstable in solution, ready to use. |
| 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 | 1.5699 mL | 7.8493 mL | 15.6986 mL |
| 5 mM | 0.314 mL | 1.5699 mL | 3.1397 mL |
| 10 mM | 0.157 mL | 0.7849 mL | 1.5699 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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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 38 reference(s) in Google Scholar.)
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