RS-33295-198: a novel, potent modulator of P-glycoprotein-mediated multidrug resistance.

Abstract

A novel multidrug resistance modulator, RS-33295-198, circumvented drug resistance in human, mouse, and Chinese hamster cell lines overexpressing P-glycoprotein. It enhanced the antiproliferative activity of doxorubicin, vincristine, etoposide, and paclitaxel and increased doxorubicin retention in multidrug-resistant hamster CHRC5 cells. RS-33295-198 modulated doxorubicin resistance in a murine P388/ADR leukemia model when administered ip via continuous minipump delivery, ip by bolus injection, and orally; it also improved the efficacy of vincristine toward P388/VCR leukemia when given ip or po. RS-33295-198 showed weak activity in enhancing doxorubicin efficacy against a multidrug-resistant human sarcoma xenograft.

• Authors: D L Slate, N A Bruno, S M Casey, N Zutshi, L J Garvin, H Wu, J R Pfister
• Journal: Anticancer research (Anticancer Res) 1995 May-Jun Vol. 15 Issue 3 Pg. 811-4 ISSN: 0250-7005 [Print] Greece
• PMID: 7645963 (Publication Type: Journal Article)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Antineoplastic Agents
• Dibenzocycloheptenes
• Quinolines
• Vincristine
• Etoposide
• Doxorubicin
• zosuquidar trihydrochloride
• Paclitaxel

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (drug effects, metabolism)
• Animals
• Antineoplastic Agents (toxicity)
• Cell Division (drug effects)
• Cell Line
• Cricetinae
• Cricetulus
• Dibenzocycloheptenes (pharmacology, therapeutic use)
• Doxorubicin (metabolism, toxicity)
• Drug Resistance, Multiple (physiology)
• Drug Synergism
• Etoposide (toxicity)
• Leukemia P388 (drug therapy)
• Mice
• Mice, Nude
• Paclitaxel (toxicity)
• Quinolines (pharmacology, therapeutic use)
• Sarcoma (drug therapy)
• Transplantation, Heterologous
• Vincristine (therapeutic use, toxicity)