Valspodar (Synonyms: Valspodar) |
| Catalog No.GC16677 |
Valspodar is a potent inhibitor of P-glycoprotein (P-gp) widely used in preclinical and clinical studies [1].
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 121584-18-7
Sample solution is provided at 25 µL, 10mM.
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Valspodar is a potent inhibitor of P-glycoprotein (P-gp) widely used in preclinical and clinical studies [1].
P-gp is a transmembrane glycoprotein which is located on cell membrane. P-gp distributes extensively and is expressed in certain cell types primarily containing liver, colon, kidney and pancreas. It also is known as multidrug resistance protein 1 (MDR1) which is pumps foreign substances out of cells. P-gp decreases the net uptake of cytotoxic drugs into the cells and mediats the efflux of these agents out of the cells, which is ATP-dependent. P-gp also overexpress in some cancer cells. P-gp plays an important role in mediating resistance to anticancer drugs and decreasing drug accumulation in multidrug-resistant cancer cells.[1]
Valspodar can reverse the resistance to mitoxantrane which is due to the expression of P-gp. The IC50 of mitoxantrane decreased from 1.6 ± 0.13 μM to 0.4 ± 0.02
μM in MDA-MB-435mdr cells pretreated with 3 mg/ml PSC. Valspodar increase the mitoxantrane intracellular accumulation by decreasing drug efflux and increasing mitoxantrone net uptake in cells.[1] The cytotoxicity was significant greater in T47D/TAMR-6 cells treated with doxorubicin and valspodar than doxorubicin only. Co-encapsulation of doxorubicin and valspodar presents a promising anticancer effect.[2] Valspodar was rapid absorpted and reachs the peak within 2 hnafter an oral dose. Valspodar showed properties of wide distribution, low hepatic extraction and mean bioavailability of 42.8% in rat.[3]
References:
[1]. Shen F, Bailey BJ, Chu S, Bence AK, Xue X, Erickson P, Safa AR, Beck WT, Erickson LC: Dynamic assessment of mitoxantrone resistance and modulation of multidrug resistance by valspodar (PSC833) in multidrug resistance human cancer cells. J Pharmacol Exp Ther 2009, 330(2):423-429.
[2]. Bajelan E, Haeri A, Vali AM, Ostad SN, Dadashzadeh S: Co-delivery of doxorubicin and PSC 833 (Valspodar) by stealth nanoliposomes for efficient overcoming of multidrug resistance. J Pharm Pharm Sci 2012, 15(4):568-582.
[3]. Binkhathlan Z, Hamdy DA, Brocks DR, Lavasanifar A: Pharmacokinetics of PSC 833 (valspodar) in its Cremophor EL formulation in rat. Xenobiotica 2010, 40(1):55-61.
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Cell experiment: |
The in vitro cytotoxicity of various formulations against T47D/TAMR-6 cells is investigated by MTT assay. A 104 T47D/TAMR-6 cells are cultured in 96-well plate containing RPMI medium and incubated overnight to allow cell attachment. After 48 hours incubation, fresh medium containing serial concentration of various drug formulations, including free DOX, DOX-L, mixture of DOX-L and free Valspodar (PSC 833), mixture of DOX-L and PSC-L and DOX/PSC-L are added. The plates are then incubated for an additional 48 hours before washing with normal saline followed by adding MTT solution (0.5 mg/mL) to each well, and incubated for 4 h at 37°C. Then, the medium is removed, and DMSO is added to dissolve the formazan crystals. The plates are mildly shaken for 10 min to ensure the dissolution of formazan. The formazan dye is measured spectrophotometrically using microplate reader at 570 nm with reference standard of 690 nm as described before. |
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Animal experiment: |
Male Sprague–Dawley rats (250-350 g) are housed in temperature-controlled rooms with 12 h of light per day. The animals had free access to food and water prior to experimentation. Rats are divided into two groups: one group (n=6) receives intravenous dose (5 mg/kg) of valspodar and the other group administered valspodar orally (10 mg/kg). Stereoselective pharmacokinetics of desbutylhalofantrine, a metabolite of halofantrine, in the rat after administration of the racemic metabolite or parent drug. After surgery, the rats are transferred to their regular holding cages and allowed free access to water, but food is withheld overnight. The next morning, rats are transferred to the metabolic cages and dosed with valspodar. |
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References: [1]. Bajelan E, et al. Co-delivery of doxorubicin and PSC 833 (Valspodar) by stealth nanoliposomes for efficient overcoming of multidrug resistance. J Pharm Pharm Sci. 2012 Sep;15(4):568-82. |
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| Cas No. | 121584-18-7 | SDF | |
| Synonyms | Valspodar | ||
| Chemical Name | PSC 833;PSC-833;PSC833 | ||
| Canonical SMILES | CC=CCC(C)C(=O)C1C(=O)NC(C(=O)N(CC(=O)N(C(C(=O)NC(C(=O)N(C(C(=O)NC(C(=O)NC(C(=O)N(C(C(=O)N(C(C(=O)N(C(C(=O)N1C)C(C)C)C)CC(C)C)C)CC(C)C)C)C)C)CC(C)C)C)C(C)C)CC(C)C)C)C)C(C)C | ||
| Formula | C63H111N11O12 | M.Wt | 1214.62 |
| Solubility | DMF: 20 mg/mL,DMF:PBS (pH 7.2)(1:3): 0.25 mg/mL,DMSO: 3 mg/mL,Ethanol: 14 mg/mL | 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 | 0.8233 mL | 4.1165 mL | 8.233 mL |
| 5 mM | 0.1647 mL | 0.8233 mL | 1.6466 mL |
| 10 mM | 0.0823 mL | 0.4117 mL | 0.8233 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
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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
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- Purity: >98.00%
- 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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