trials to Flavopiridol evaluate the efficacy of paclitaxel toxicity t In the presence and absence of zosuquidar compare. Should substantially a dose of 225 mg m 2 in the absence of paclitaxel zosuquidar and a dose of 175 mg m 2 in the presence of a lead zosuquidar Hnlichen time when the plasma concentration of paclitaxel remains above 0.1 mmol L 1 and AUC simultaneously. Therefore, these doses are necessary to reduce the likelihood k pharmacodynamic effects of P gp inhibition on the effect of the disease, which simply run pharmacokinetic interactions Nnte define. ABC transporters are membrane proteins Two transmembrane NEN and unique nucleotide binding Dom NEN, the production of energy from ATP hydrolysis composed actively transport a variety of compounds across the membrane.
These vans go Ren to the superfamily of ABC proteins Into seven distinct subfamilies of sequence homology and Dom divided nenorganisation. Among others seem three members of the family of DMXAA ABC transporters ABCB1, ABCC1 and ABCG2, play an r In the development of tuberculosis in cancer cells important. Some members of this family are also active transport a variety of substrates, including normal ions, sugars, amino acids, Lipids, toxins, and cytotoxic drugs. Essentially, if they are over-expressed ABC drug transporters in cancer cells, k They can cross-resistance to multiple drugs of different chemical classes by actively participating lend expiring cytostatics, which entered the cumulative drug under the actual product chlichen level and chemotherapy th MDR.
Zus Tzlich least 15 genetic diseases with defects 20 ABC superfamily, such as cystic fibrosis, Tangier disease, Dubin Johnson syndrome, and pseudoxanthoma elasticum are connected. P-glycoprotein ABCB1 was determined the first drug human ABC transporters and has been studied extensively. He tr # adds a variety of compounds, including some of the most popular anti-cancer drugs such as taxanes, anthracyclines and alkaloids of the periwinkle. have failed because all attempts, crystals suitable for human ABCB1 R ntgenkristallographie obtained so far, the structure of the ABCB1 is provided on the basis of biochemical studies, mutational analysis and structural information such as bacterial counterparts Sav1866.
Although a structure having low Aufl Has been described measurement based on electron microscopy, the predicted structure of human ABCB1 to two H halves Each with a transmembrane Ne transmembrane six helices and one NBD exist, with coils 4, 5 and 6 the N-terminal half of H and propellers 10, 11 and 12 in the C-terminal H half for forming the support site transportation. ABCC1 ABCC1 and ABCG2 was the first member of the family, the MRP was found to MDR by Cole et al zusammenh Nts Structurally ABCC1 is expected to have three transmembrane helices containing17 TMD. Unlike ABCB1 TMD has another five transmembrane helices with