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pegylated liposomal doxorubicin + valspodar
- Development stage
- Unknown
- Lead developer
- Washington University School of Medicine
- Modality
- Lipid-based Nanoparticles → Nanoparticles → Drug Delivery Systems, Small Molecules
- Administration
- Intravenous
01
Overview
A combination therapy consisting of pegylated liposomal doxorubicin (Doxil) and the P-glycoprotein (P-gp) inhibitor valspodar (PSC 833). Doxorubicin is an anthracycline chemotherapy agent that works by intercalating DNA and inhibiting topoisomerase II, leading to cell death. Valspodar is a non-immunosuppressive cyclosporine D derivative that acts as a potent inhibitor of the MDR1 efflux pump (P-glycoprotein). The rationale for this combination is to overcome multidrug resistance in tumors like Kaposi's sarcoma and advanced solid tumors, where P-gp expression often limits the efficacy of doxorubicin by pumping the drug out of the cells. This specific combination was investigated in a Phase 1 study by Washington University School of Medicine to determine the maximum tolerated dose and toxicity profile.
- Brand names
- Doxil
- Other names
- pegylated liposomal doxorubicin hydrochloridevalspodar
02
Targets
ABCB1 (P-glycoprotein)DNATOP2A (DNA topoisomerase II)
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