of Ransporters, the pharmacokinetics and efficacy of medicines. Thus m Possible drug compounds usually examined to determine whether it is substrates for ABC transporters. Therefore mediates the synthesis of drugs are medicinal chemists analogues multidrug resistance of ABC transporters deal. For example, camptothecin analogues were con ABCG2 substrate specificity and tested us t. Less polar WYE-354 compounds have to be used as substrates for ABCB1 or ABCG2. It also develops drugs for longer substrates for the transport of dissolved Most substances, proteins A superfamily of membrane transport shown recently, that play an r Can facilitate important in the pharmacokinetics of drugs to prevent the adoption of chemotherapy drugs and MDR. R Solute the Tr hunters in cancer chemotherapy has been recently discussed elsewhere.
However, Fasudil there is no conclusive evidence yet experimental overexpression of gel Most transporters in resistant tumor tissue. Develop compounds specifically target cancer cells multidrug Despite considerable efforts, inhibitors and modulators to discover natural products drug ABC transporters, there are no inhibitors currently used in clinical treatment. Verapamil, a first ABCB1 modulators present effectively reverse MDR mediated by ABCB1 was also one of the first compounds have a high toxicity t guarantees overexpress ABCB1 in Chinese hamster ovary cells. This sensitivity or hypersensitivity warranty provides researchers with an alternative approach to hedge against MDR induced by the overexpression of ABC transporters drugs k Can fight.
Many research groups are compounds whose toxicity t Substantial warranty MDR cell lines, can induce apoptosis specifically looking at MDR cell lines. These compounds have potential applications exist in the clinic, either alone or in combination with cancer chemotherapeutic agents already. Examples of compounds having a weight sensitivity Hrleistet are listed in Table 2. In 1987, Cano Gauci and Riordan found that overexpression of ABCB1 hypersensitive in the Chinese hamster were on calcium channel blockers such as verapamil, nifedipine and the calmodulin inhibitor trifluoperazine. This hypersensitivity is both independently Ngig and calcium-independent-Dependent intracellular Re accumulation of verapamil. Subsequent studies by Warr et al.
in 1988 showed that in addition to calcium channel blockers, vincristine-resistant CHO cells are also hypersensitive active on membrane agents quinidine, suggesting that calcium-channels the main objective of this hypersensitivity or toxicity t warranty. More recently Karwatsky et al. observed concentrated on mechanistic aspects of hypersensitivity MDR CHO cells verapamil. It was concluded that apoptosis is caused by the increase in the production of reactive oxygen species in the MDR cells. Furthermore, this toxicity T guarantee with increased FITTINGS ATPase activity T correlated independently Ngig of the activity t of p53 and