Novel microtubule-targeting agents - the XXXX .

@entity18553 @entity1262 @entity6023 @entity21597 @entity137 @entity0 @entity5 @entity416 @entity72397 @entity19878 @entity294 @entity3907 @entity72396 @entity57117 @entity14514
@entity21597 are a new class of antimicrotubule agents currently in clinical trials. Their chemical structures are distinct from @entity6023 and are more amenable to synthetic modification. Six @entity21597 have been studied in preclinical and clinical trials: @entity14514 ( @entity14514 ), @entity19878 ( @entity19878 ), @entity72396 , @entity18553 (ZK-EPO), @entity57117 ( @entity57117 ), and @entity72397 . In vitro data have shown increased potency in @entity3907 -sensitive and @entity3907 -resistant @entity5 cell lines. This enhanced cytotoxic effect has been attributed to epothilone being a poor substrate for @entity1262 drug resistance protein and having high affinity to the various beta tubulin isoforms. Phase I clinical data have shown different dose-limiting @entity137 for each of the @entity21597 . These effects are drug specific, dose specific, and schedule of administration specific. While @entity294 and myelosuppression are the dose-limiting @entity137 for @entity14514 and @entity72396 , respectively, @entity137 , as seen with @entity6023 , is the dose-limiting @entity137 of @entity19878 , @entity18553 , and @entity57117 . In an effort to decrease @entity137 , investigators have modified dosing schedules with limited success. @entity19878 has the most mature clinical results with published phase II and III data, and regulatory approval for clinical use in the treatment of @entity0 . @entity19878 has also been combined with other anticancer agents and has regulatory approval in combination with @entity416 for heavily treated @entity0 .
