Derand, Renaud; Bulteau-Pignoux, Laurence; Mettey, Yvette; Zegarra-Moran, Olga; Howell, L. Daniel; Randak, Christoph; Galietta, Luis J. V.; Cohn, Jonathan A.; Norez, Caroline; Romio, Leila; Vierfond, Jean-Michel; Joffre, Michel; Becq, Frederic published the artcile< Activation of G551D CFTR channel with MPB-91: regulation by ATPase activity and phosphorylation>, Synthetic Route of 2905-54-6, the main research area is cystic fibrosis transmembrane conductance regulator mutant activation MPB91 preparation; benzoquinolizinium derivative preparation activation CFTR chloride channel mutant.
We have designed and synthesized benzo[c]quinolizinium derivatives and evaluated their effects on the activity of G551D cystic fibrosis transmembrane conductance regulator (CFTR) expressed in Chinese hamster ovary and Fisher rat thyroid cells. We demonstrated, using iodide efflux, whole cell patch clamp, and short-circuit recordings, that 5-butyl-6-hydroxy-10-chlorobenzo[c]quinolizinium chloride (MPB-91) restored the activity of G551D CFTR (EC50 = 85 μM) and activated CFTR in Calu-3 cells (EC50 = 47 μM). MPB-91 has no effect on the ATPase activity of wild-type and G551D NBD1/R/GST fusion proteins or on the ATPase, GTPase, and adenylate kinase activities of purified NBD2. The activation of CFTR by MPB-91 is independent of phosphorylation because (1) kinase inhibitors have no effect and (2) the compound still activated CFTR having 10 mutated protein kinase A sites (10SA-CFTR). The new pharmacol. agent MPB-91 may be an important candidate drug to ameliorate the ion transport defect associated with CF and to point out a new pathway to modulate CFTR activity.
American Journal of Physiology published new progress about CFTR (cystic fibrosis transmembrane conductance regulator) Role: BSU (Biological Study, Unclassified), PRP (Properties), BIOL (Biological Study). 2905-54-6 belongs to class chlorides-buliding-blocks, and the molecular formula is C8H6Cl2O2, Synthetic Route of 2905-54-6.
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