RS-33295-198: a novel, potent modulator of P-glycoprotein-mediated multidrug resistance.
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.
Slate
D L
DL
Institute of Biochemistry and Cell Biology, Palo Alto, CA, USA.
Bruno
N A
NA
Casey
S M
SM
Zutshi
N
N
Garvin
L J
LJ
Wu
H
H
Pfister
J R
JR
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D003986:Dibenzocycloheptenes / Q000494:pharmacology* / Q000627:therapeutic use; D004317:Doxorubicin / Q000378:metabolism / Q000633:toxicity; D018432:Drug Resistance, Multiple / Q000502:physiology*; D004357:Drug Synergism; D005047:Etoposide / Q000633:toxicity; D007941:Leukemia P388 / Q000188:drug therapy*; D051379:Mice; D008819:Mice, Nude; D017239:Paclitaxel / Q000633:toxicity; D011804:Quinolines / Q000494:pharmacology* / Q000627:therapeutic use; D012509:Sarcoma / Q000188:drug therapy; D014183:Transplantation, Heterologous; D014750:Vincristine / Q000627:therapeutic use / Q000633:toxicity
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D003986:Dibenzocycloheptenes; D011804:Quinolines; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; C095179:zosuquidar trihydrochloride; D017239:Paclitaxel