Studies with RP 56976 (taxotere): a semisynthetic analogue of taxol.
RP 56976 (taxotere), a new semisynthetic analogue of taxol, is a potentially important chemotherapeutic agent for the treatment of cancer. We report here that this drug is a potent inhibitor of cell replication and, like taxol, promotes the in vitro assembly of stable microtubules in the absence of guanosine triphosphate and induces microtubule-bundle formation in cells. Compared with taxol, RP 56976 is slightly more active as a promoter of tubulin polymerization. As an inhibitor of cell replication, RP 56976 is 2.5-fold more potent than taxol in J774.2 and P388 cells and at least 5-fold more potent in taxol-resistant cells.
Ringel
I
I
Department of Pharmacology, Hadassah Medical School, Hebrew University, Jerusalem, Israel.
Horwitz
S B
SB
D000470:Alkaloids / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D000077143:Docetaxel; D006160:Guanosine Triphosphate / Q000378:metabolism; D007945:Leukemia, Lymphoid / Q000188:drug therapy / Q000473:pathology; D008870:Microtubules / Q000187:drug effects; D017239:Paclitaxel; D013329:Structure-Activity Relationship; D043823:Taxoids; D014407:Tumor Cells, Cultured
D000470:Alkaloids; D043823:Taxoids; D000077143:Docetaxel; D006160:Guanosine Triphosphate; D017239:Paclitaxel