The analogs showed an unique conduct toward cells with acquired resistance against the pure solution disorazole C1, which owe their resistance phenotype a minimum of partly to overexpression of the ABCB1 p glycoprotein pump. Dictyostatins absence cross resistance to paclitaxel, epothilone B, and disorazole C1 Drug resistance is an issue with MT perturbing MAPK assay agents in clinical use. One clinically important resistance mechanism is overexpression of p glycoprotein efflux pumps. In cultured cells, additional resistance mechanisms have been observed that contain tubulin mutations induced by longterm culture of cell lines in the existence of MT perturbing agencies, while such drug induced mutations have not been present in clinical samples. In three such mobile types with mutant tubulin, the newest analogs seemed less cross resistant than the natural product, and retained activity against both paclitaxel and epothilone W resistant cells. The 1A9/PTX10 cell line contains a Phe270 Val mutation that’s found inside the taxane binding site and confers 49 fold resistance to paclitaxel. Consistent with our previous studies with dictyostatin and 6 epi dictyostatin, cross resistance was reduced to 10 fold with the new analogs. Needlessly to say, no cross resistance was Organism present in the 1A9/PTX22 cell line, which has a Ala364 Thr mutation that is next to the taxane binding pocket. In epothilone W resilient A 549 cells with a 292Gln Glu mutation, which will be located at the periphery of the taxane pocket and makes contact with epothilone however not paclitaxel, the analogs showed just a 12 18 collapse combination resistance compared with epothilone B. The data suggest that reduction of the terminal double bond doesn’t change the function of tubulin binding. They are consistent with a function of binding to tubulin as proposed by Canales et al. Cyclopamine molecular weight that involves the taxane binding pocket but not residues away from pocket that make contact with the taxane side chain. All agencies were subnanomolar inhibitors of wild type HeLa cells. Paclitaxel and vinblastine were 502 and 1395 fold less-active, respectively, in the immune cells. Knockdown of the Pglycoprotein push, ABCB1, restored many, of their activity. In comparison, the HeLa/DZR cells showed only minor cross resistance to the dictyostatin analogs which was completely reversed by ABCB1 knockdown. The data suggest the dictyostatins may be only weak substrates for ABCB1. Moreover, since the HeLa/DZR cells were generated by just one exposure to the mutagen ethyl methane sulfonate followed by a step-wise increased disorazole C1 exposure, it’s likely that resistance mechanisms other than elevated ABCB1 exist, but these do not appear to influence cellular sensitivity to the dictyostatin analogs.