CFTR-F508del Corrector II, Corr-4a

A cell-permeable bisaminomethylbithiazole compound that is reported to rescue/correct the folding defect of CFTR ΔF508 mutant via direct interaction and promote proper trafficking/glycosylation and surface expression in both transfected cells and primary airway epithelial cells from ΔF508-homozygous patients, while exhibiting little correcting effect toward N1303K-CFTR, P574H-CFTR, M345T-DRD4 (dopamine receptor 4), or G268V-ABCA1/CD243 /MDR1/ P-gp mutant. Reported to enhance the folding efficiency of both ΔF508 (by 3-fold at 10µM in FRT cells) and wild-type CFTR (by up to 70%), delay the ER-associated degradation of the core-glycosylated ΔF508 (by 30% at 10µM in FRT cells), and increase the stability of low-temperature resuced ΔF508 mutant on the plasma membrane (by 1.7-fold at 10µM in FRT cells). Corr-4a is shown to be more effective than VRT-325/CFcor-325 n restoring forskolin-stimulated CFTR activity in FRT and A549 ΔF508-CFTR transfectants. Unlike VRT-532 Corr-4a does not affect mutant CFTR channel gating activity.

Toxicity: Standard Handling (A)

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Pedemonte, N., et al. 2010. Am. J. Physiol. Cell Physiol.298, C866.
Young, A., et al. 2009. Biochem. J.421, 377.
Wang, Y., et al. 2007. J. Biol. Chem.282, 33247.
Wang, Y., et al. 2007. Mol. Pharmacol.71, 751.
Wang, Y., et al. 2007. Biochem. J.406, 257.
Pedemonte, N., et al. 2005. J. Clin. Invest.115, 2564.

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany