What Is Valspodar? Definition and What Research Reports

Definition

Valspodar (also written PSC 833 or SDZ PSC 833) is a semi-synthetic cyclic peptide derived from cyclosporin D, one of the cyclosporin family of cyclic undecapeptides originally isolated from fungal sources. Unlike cyclosporin A, valspodar is generally described as lacking meaningful immunosuppressive activity, and it was developed instead as a so-called "second-generation" inhibitor of P-glycoprotein (P-gp, encoded by the ABCB1/MDR1 gene), the ATP-binding cassette efflux pump associated with multidrug resistance in tumour cells and with drug transport at biological barriers. In the published literature the word "valspodar" almost always signals a transporter-inhibition context: it names a reference compound used to test whether a molecule of interest is handled by P-glycoprotein. This page is for educational purposes only and is not medical advice; consult a licensed physician for any question about health, treatment or medication.

What Class of Molecule Is It?

Valspodar sits in the peptide world by structure rather than by signalling biology. Cyclosporins are cyclic undecapeptides — eleven amino acid residues, several of them N-methylated and non-proteinogenic, closed into a ring. That ring structure makes them unusually membrane-permeable and metabolically stable for peptides, which is why cyclosporin analogues appear repeatedly in pharmacology as orally available scaffolds. Valspodar is a chemically modified cyclosporin D analogue. It is therefore not a "peptide hormone," a growth-hormone secretagogue, or a receptor agonist of the kind usually catalogued on peptide reference pages; it belongs instead to the macrocyclic peptide natural-product class, and its recorded activity is on a membrane transporter rather than a hormone receptor.

How the term is used

• As a pharmacological tool. Researchers add valspodar to cell-based assays to block P-glycoprotein, then ask whether accumulation, toxicity or permeability of a test compound changes.
• As a comparator. When a new or natural-product inhibitor is characterised, valspodar frequently appears as the established reference against which reversal of resistance is judged.
• As a historical clinical-development term. Valspodar was investigated in oncology trials during the era when P-gp inhibition was pursued as a resistance-reversal strategy; compendia of drug development, such as the "Gateways to clinical trials" series, catalogued agents in development across therapeutic areas (PMID 21225019).

What the Published Literature Reports

Multidrug resistance and transporter pharmacology

The bulk of the valspodar literature is in vitro transporter work. A 2017 ethnopharmacology paper examined reversal of multidrug resistance by Marsdenia tenacissima and its main active polyoxypregnane constituents, the classic experimental design in which a candidate resistance-reversing agent is assessed against established P-glycoprotein inhibition (PMID 28363522). A 2023 comparative study reported on ABCB1-dependent efflux of anthracyclines and their metabolites and discussed the consequences for cancer resistance (PMID 37753851). A 2014 investigation asked whether PARP inhibitors behave as P-glycoprotein substrates, using transporter assays to make that determination (PMID 24700236). A 2023 preprint reported that the multidrug resistance transporter P-glycoprotein conferred resistance to ferroptosis inducers, extending the efflux question to a newer class of cell-death-inducing compounds (PMID 36945397).

Related work has looked at what happens to cells when the pump is blocked. A 2014 study in Molecules examined the effects of P-glycoprotein and its inhibitors on apoptosis in K562 leukaemia cells (PMID 25157469). A 2024 screening paper surveyed interactions between photosensitisers and ATP-binding cassette transporters in vitro, the kind of survey in which established transporter inhibitors are used to assign substrate status (PMID 39403604).

Barriers, absorption and toxicology models

Because P-glycoprotein also sits at the intestine, skin and other barriers, valspodar-era transporter methods appear outside oncology. A 2020 paper verified P-glycoprotein function at the dermal barrier using both static diffusion cells and a dynamic "skin-on-a-chip" microfluidic device (PMID 32854319). A 2016 study characterised intestinal permeability and P-glycoprotein-mediated efflux transport of ticagrelor in Caco-2 monolayers (PMID 27416295). In food toxicology, a 2018 paper investigated the role of P-glycoprotein in deoxynivalenol-mediated toxicity in vitro (PMID 29174985). A 2020 pharmaceutics study reported that an excipient boosted drug bioavailability in men but not in women, a result discussed in the context of efflux-transporter modulation (PMID 32710919).

An antiviral report

Outside the resistance field, a 2021 study in Antiviral Research reported that valspodar limited human cytomegalovirus infection and dissemination, placing the compound in a virology rather than an oncology context (PMID 34197862). That paper is the single most direct valspodar-titled entry in the set summarised here; the other reports are transporter studies in which P-glycoprotein inhibition is the shared subject matter.

Where Valspodar Appears: Summary Table

Tolerability and Adverse Events: What Studies Report

The verified papers summarised on this page are predominantly laboratory studies — cell monolayers, isolated transporter assays, diffusion cells and microfluidic barrier models — rather than clinical safety trials. The dermal-barrier work used diffusion cells and a skin-on-a-chip device (PMID 32854319), the intestinal work used Caco-2 monolayers (PMID 27416295), and the apoptosis work used K562 cells (PMID 25157469). None of these designs generates human adverse-event data, and no human tolerability figures are stated here because the cited set does not contain them. One drug-development compendium in the cited set catalogued agents moving through clinical trials across indications (PMID 21225019), but a catalogue entry is not a safety dataset. Readers comparing sources should note that transporter inhibition by design alters how co-administered substrates are handled, which is the mechanistic point of the assays described above (PMID 24700236).

Terms Commonly Confused With Valspodar

• Cyclosporin A — the immunosuppressant parent scaffold; valspodar is a distinct cyclosporin D analogue described as non-immunosuppressive.
• P-glycoprotein / ABCB1 / MDR1 — the transporter, not the inhibitor. Papers on efflux of substrates such as anthracyclines describe the transporter's behaviour (PMID 37753851).
• Tariquidar, elacridar, verapamil — other compounds catalogued in the P-gp inhibitor literature; they are chemically unrelated to the cyclic peptide scaffold.
• "Peptide therapeutics" — valspodar is a peptide by chemistry but is not part of the metabolic or regenerative peptide categories that term usually implies.

Research Status

Valspodar is discussed in the scientific record as an investigational compound and laboratory reagent. It is not an approved therapeutic product in the United States, and materials of this type are typically handled under research-use-only labelling in laboratory settings. This entry is definitional: it records what the term means and what the cited reports examined, and it does not describe administration, quantities, schedules or outcomes in people.

References

• Valspodar limits human cytomegalovirus infection and dissemination (Antiviral Research, 2021)
• Comparative study on ABCB1-dependent efflux of anthracyclines and their metabolites: consequences for cancer resistance (Xenobiotica, 2023)
• Reversal of multidrug resistance by Marsdenia tenacissima and its main active ingredients polyoxypregnanes (Journal of Ethnopharmacology, 2017)
• PARP Inhibitors as P-glycoprotein Substrates (Journal of Pharmaceutical Sciences, 2014)
• The Multidrug Resistance Transporter P-glycoprotein Confers Resistance to Ferroptosis Inducers (bioRxiv, 2023)
• Screening of photosensitizers-ATP binding cassette (ABC) transporter interactions in vitro (Cancer Drug Resistance, 2024)
• Verification of P-Glycoprotein Function at the Dermal Barrier in Diffusion Cells and Dynamic "Skin-On-A-Chip" Microfluidic Device (Pharmaceutics, 2020)
• Intestinal permeability and P-glycoprotein-mediated efflux transport of ticagrelor in Caco-2 monolayer cells (Fundamental & Clinical Pharmacology, 2016)
• Role of P-glycoprotein in deoxynivalenol-mediated in vitro toxicity (Toxicology Letters, 2018)
• Boosting drug bioavailability in men but not women through the action of an excipient (International Journal of Pharmaceutics, 2020)
• Effects of P-glycoprotein and its inhibitors on apoptosis in K562 cells (Molecules, 2014)
• Gateways to clinical trials (Methods and Findings in Experimental and Clinical Pharmacology, 2010)