Valspodar

Description

PSC 833 is a non-immunosuppressant derivative of cyclosporine and potent multidrug-resistance (MDR) modulator. It restores sensitivity of MDR-P388 murine leukemia cells to cytostatic agents when used at concentrations of 70, 33, 45, 34, and 26 nM in combination with colchicine, vincristine , daunorubicin , doxorubicin , and etoposide , respectively. PSC 833 inhibits basal-to-apical transport and increases apical-to-basal transport of [¹⁴C]docetaxel in LLC-GA5-COLO150 cells that overexpress human P-glycoprotein (P-gp). In vivo, PSC 833 increases survival time in MDR-P388 tumor-bearing mice and in an MDR-L1210 leukemia mouse xenograft model when administered in combination with doxorubicin. PSC 833 also prolongs the anti-hyperalgesic effects of intraperitoneally administered pregabalin in a mouse model of cold stress-induced central pain.

Chemical properties

White Solid

The Uses of Valspodar

Valspodar/ PSC-833 has been used as a ABCB1 (P-glycoprotein) inhibitor.

The Uses of Valspodar

Antineoplastic adjunct (chemosensitizer).

The Uses of Valspodar

Valspodar(PSC-833), a 2nd-generation ABC transporter inhibitor, limits HCMV infection as demonstrated by the decrease in IE2 expression of virus-infected cells. As a cyclosporin D analog, it has been shown to be a much more effective inhibitor of MDR than cyclosporin A and to be less toxic[1-2].

What are the applications of Application

PSC 833 is a P-glycoprotein (P-gp, Mdr-1) modulator shown to inhibit P-gp-mediated multidrug-resistance (MDR).

Definition

ChEBI: SDZ PSC 833 is a homodetic cyclic peptide.

brand name

Amdray (Novartis).

Biochem/physiol Actions

Valspodar is a nonimmunosuppressive cyclosporin analog and potent P-glycoprotein (MDR1) inhibitor. Valspodar reverses multidrug resistance (MDR) by inhibiting cellular drug efflux mediated by P-glycoprotein.

Cytotoxicity

Cells treated with increasing concentrations of valspodar over a 9-day period show minimal cytotoxicity. It appears to be neither immunosuppressive nor nephrotoxic with the ability to achieve levels in the blood (1 μm) capable of reversing drug resistance without excessive toxicity[1].

Storage

Store at -20°C

References

[1] Friedenberg W, et al. Phase III study of PSC-833 (valspodar) in combination with vincristine, doxorubicin, and dexamethasone (valspodar/VAD) versus VAD alone in patients with recurring or refractory multiple myeloma (E1A95). Cancer, 2006; 106: 830-838.
[2] Parsons J, et al. Valspodar limits human cytomegalovirus infection and dissemination. Antiviral Research, 2021; 193: 105124.