Valspodar
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    WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 558303

CAS#: 121584-18-7

Description: Valspodar, also known as PSC-833, is an analogue of cyclosporin-A. Valspodar inhibits p-glycoprotein, the multidrug resistance efflux pump, thereby restoring the retention and activity of some drugs in some drug-resistant tumor cells. This agent also induces caspase-mediated apoptosis.

Chemical Structure

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Valspodar
CAS# 121584-18-7
Instruction

Theoretical Analysis

MedKoo Cat#: 558303
Name: Valspodar
CAS#: 121584-18-7
Chemical Formula: C63H111N11O12
Exact Mass: 1,213.84
Molecular Weight: 1,214.620
Elemental Analysis: C, 62.30; H, 9.21; N, 12.68; O, 15.81

Price and Availability

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1mg USD 550 2 Weeks
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Synonym: PSC833; PSC833; PSC833; SDZ PSC 833; Sdz-psc-833; Valspodar

IUPAC/Chemical Name: (3S,6S,9S,12R,15S,18S,21S,24S,30S,33S)-6,9,18,24-tetraisobutyl-3,21,30-triisopropyl-1,4,7,10,12,15,19,25,28-nonamethyl-33-((R,E)-2-methylhex-4-enoyl)-1,4,7,10,13,16,19,22,25,28,31-undecaazacyclotritriacontan-2,5,8,11,14,17,20,23,26,29,32-undecaone

InChi Key: YJDYDFNKCBANTM-QCWCSKBGSA-N

InChi Code: InChI=1S/C63H111N11O12/c1-26-27-28-41(16)53(76)52-57(80)67-49(38(10)11)61(84)68(19)33-48(75)69(20)44(29-34(2)3)56(79)66-50(39(12)13)62(85)70(21)45(30-35(4)5)55(78)64-42(17)54(77)65-43(18)58(81)71(22)46(31-36(6)7)59(82)72(23)47(32-37(8)9)60(83)73(24)51(40(14)15)63(86)74(52)25/h26-27,34-47,49-52H,28-33H2,1-25H3,(H,64,78)(H,65,77)(H,66,79)(H,67,80)/b27-26+/t41-,42+,43-,44+,45+,46+,47+,49+,50+,51+,52+/m1/s1

SMILES Code: O=C([C@H](C(C)C)N(C)C([C@H](CC(C)C)N(C)C([C@H](CC(C)C)N(C)C([C@@H](C)NC([C@H](C)NC([C@H](CC(C)C)N(C)C([C@H](C(C)C)NC([C@H](CC(C)C)N(C)C(CN(C)C([C@H](C(C)C)N1)=O)=O)=O)=O)=O)=O)=O)=O)=O)N(C)[C@@H](C([C@H](C)C/C=C/C)=O)C1=O

Appearance: White to beige solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >5 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info: PSC-833 is a non-immunosuppressive cyclosporin derivative that potently and specifically inhibits P-gp.  In vitro experiments indicate that PSC-833 interacts directly with P-gp with high affinity and probably interferes with the ATPase activity of P-gp. Studies in multidrug resistant tumor models confirm P-gp as the in vivo target of PSC-833 and demonstrate the ability of PSC-833 to reverse MDR leukemias and solid tumors in mice. Presently, PSC-833 is being evaluated in the clinic.   According to wikipedia.com. Previous studies in animal models have found it to be effective at preventing cancer cell resistance to chemotherapeutics, but these findings did not translate to clinical success. (http://en.wikipedia.org/wiki/Psc833).        

Biological target:
In vitro activity:
In vivo activity:

Preparing Stock Solutions

The following data is based on the product molecular weight 1,214.62 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
In vitro protocol:
In vivo protocol:

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1: 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 Sep;15(4):568-82. PubMed PMID: 23106959.

2: Binkhathlan Z, Elhasi S, Brocks DR, Lavasanifar A. Characterization of the self assembly of methoxy poly(ethylene oxide)-block-poly(α-benzyl carboxylate-ε-caprolactone) for the solubilization and in vivo delivery of valspodar. Curr Drug Deliv. 2012 Mar;9(2):164-71. PubMed PMID: 22283648.

3: Kuemmerle A, Yan H, Krueger T, Buclin T, Braissant O, Henry H, Ris HB, Decosterd LA. P-glycoprotein modulation by valspodar and cyclosporin does not increase tumor uptake of doxorubicin administered via isolated lung perfusion to rats bearing sarcoma lung metastases. Anticancer Res. 2011 Jun;31(6):2121-8. PubMed PMID: 21737631.

4: Kolitz JE, George SL, Marcucci G, Vij R, Powell BL, Allen SL, DeAngelo DJ, Shea TC, Stock W, Baer MR, Hars V, Maharry K, Hoke E, Vardiman JW, Bloomfield CD, Larson RA; Cancer and Leukemia Group B. P-glycoprotein inhibition using valspodar (PSC-833) does not improve outcomes for patients younger than age 60 years with newly diagnosed acute myeloid leukemia: Cancer and Leukemia Group B study 19808. Blood. 2010 Sep 2;116(9):1413-21. doi: 10.1182/blood-2009-07-229492. Epub 2010 Jun 3. PubMed PMID: 20522709; PubMed Central PMCID: PMC2938834.

5: Binkhathlan Z, Hamdy DA, Brocks DR, Lavasanifar A. Development of a polymeric micellar formulation for valspodar and assessment of its pharmacokinetics in rat. Eur J Pharm Biopharm. 2010 Jun;75(2):90-5. doi: 10.1016/j.ejpb.2010.03.010. Epub 2010 Mar 21. PubMed PMID: 20332028.

6: O'Brien MM, Lacayo NJ, Lum BL, Kshirsagar S, Buck S, Ravindranath Y, Bernstein M, Weinstein H, Chang MN, Arceci RJ, Sikic BI, Dahl GV. Phase I study of valspodar (PSC-833) with mitoxantrone and etoposide in refractory and relapsed pediatric acute leukemia: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2010 May;54(5):694-702. doi: 10.1002/pbc.22366. PubMed PMID: 20209646; PubMed Central PMCID: PMC2838930.

7: Binkhathlan Z, Hamdy DA, Brocks DR, Lavasanifar A. Pharmacokinetics of PSC 833 (valspodar) in its Cremophor EL formulation in rat. Xenobiotica. 2010 Jan;40(1):55-61. doi: 10.3109/00498250903331056. PubMed PMID: 19903013.

8: 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 Aug;330(2):423-9. doi: 10.1124/jpet.109.153551. Epub 2009 May 7. PubMed PMID: 19423841; PubMed Central PMCID: PMC2713081.

9: Binkhathlan Z, Somayaji V, Brocks DR, Lavasanifar A. Development of a liquid chromatography-mass spectrometry (LC/MS) assay method for the quantification of PSC 833 (Valspodar) in rat plasma. J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Jun 15;869(1-2):31-7. doi: 10.1016/j.jchromb.2008.05.003. Epub 2008 May 10. PubMed PMID: 18514043.

10: Lhommé C, Joly F, Walker JL, Lissoni AA, Nicoletto MO, Manikhas GM, Baekelandt MM, Gordon AN, Fracasso PM, Mietlowski WL, Jones GJ, Dugan MH. Phase III study of valspodar (PSC 833) combined with paclitaxel and carboplatin compared with paclitaxel and carboplatin alone in patients with stage IV or suboptimally debulked stage III epithelial ovarian cancer or primary peritoneal cancer. J Clin Oncol. 2008 Jun 1;26(16):2674-82. doi: 10.1200/JCO.2007.14.9807. PubMed PMID: 18509179.