Small-molecule correctors of defective ΔF508-CFTR cellular processing identified by high-throughput screening

Journal of Clinical Investigation

Volumn 115, Issue 9, 2005, Pages 2564-2571

  Pedemonte, Nicoletta ^a,b   Lukacs, Gergely L ^c   Du, Kai ^c   Caci, Emanuela ^b   Zegarra Moran, Olga ^b   Galietta, Luis J V ^b   Verkman, Alan S ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b G GASLINI INSTITUTE   (Italy)

^c HOSPITAL FOR SICK CHILDREN RESEARCH INSTITUTE   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

BISAMINOMETHYLTHIAZOLE; CHLORIDE; CHLORIDE CHANNEL; DOPAMINE RECEPTOR; HALIDE; IODIDE; PHENYLALANINE; PYRIMIDINONE DERIVATIVE; QUINAZOLINE DERIVATIVE; THIAZOLE DERIVATIVE; TRANSMEMBRANE CONDUCTANCE REGULATOR; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; BRONCHUS MUCOSA; CHLORIDE CURRENT; CONTROLLED STUDY; CYSTIC FIBROSIS; ENDOPLASMIC RETICULUM; EPITHELIUM CELL; GLYCOSYLATION; HIGH THROUGHPUT SCREENING; MEMBRANE CURRENT; NONHUMAN; PRIORITY JOURNAL; PROTEIN FOLDING;

ANIMALS; CELLS, CULTURED; CYSTIC FIBROSIS; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; DRUG DESIGN; ENZYME INHIBITORS; EPITHELIAL CELLS; FORSKOLIN; GENISTEIN; HUMANS; IODIDES; LUMINESCENT PROTEINS; MOLECULAR STRUCTURE; MUTATION; PYRIMIDINONES; RESPIRATORY MUCOSA; THIAZOLES;

EID: 24644464284     PISSN: 00219738     EISSN: None     Source Type: Journal    
DOI: 10.1172/JCI24898     Document Type: Article

References (37)

1. Bobadilla, J.L., Macek, M., Jr., Fine, J.P., and Fartell, P.M. 2002. Cystic fibrosis: a worldwide analysis of CFTR mutations - correlation with incidence data and application to screening [review]. Hum. Mutat. 19:575-606.
2. Pilewski, J.M., and Frizzell, R.A. Role of CFTR in airway disease. 1999. Physiol. Rev. 79:S215-S255.
3. Sheppard, D.N., and Welsh, M.J. 1999. Structure and function of the CFTR chloride channel. Physiol. Rev. 79:S23-S45.
4. Denning, G.M., et al. 1992. Processing of mutant cystic fibrosis transmembrane conductance regulator is temperature-sensitive. Nature. 358:761-764.
5. Lukacs, G.L., et al. 1994. Conformational maturation of CFTR but not its mutant counterpart (ΔF508) occurs in the endoplasmic reticulum and requires ATP. EMBO J. 13:6076-6086.
6. Kopito, R.R. 1999. Biosynthesis and degradation of CFTR. Physiol. Rev. 79:S167-S173.
7. Du, K., Sharma, M., and Lukacs, G.L. 2005. The ΔF508 cystic fibrosis mutation impairs domain-domain interactions and arrests post-translational folding of CFTR. Nat. Struct. Mol. Biol. 12:17-25.
8. Sharma, M., Benharouga, M., Hu, W., and Lukacs, G.L. 2001. Conformational and temperature-sensitive stability defects of the ΔF508 cystic fibrosis transmembrane conductance regulator in post-endoplasmic reticulum compartments. J. Biol. Chem. 276:8942-8950.
9. Gentzsch, M., et al. 2004. Endocytic trafficking routes of wild type and ΔF508 cystic fibrosis transmembrane conductance regulator. Mol. Biol. Cell. 5:2684-2696.
10. Sato, S., Ward, C.L., Krouse, M.E., Wine, J.J., and Kopito, R.R. 1996. Glycerol reverses the misfolding phenotype of the most common cystic fibrosis mutation. J. Biol. Chem. 271:635-658.
11. Rubenstein, R.C., Egan, M.E., and Zeitlin, P.L. 1997. In vitro pharmacologic restoration of CFTR-mediated chloride transport with sodium 4-phenylbutyrate in cystic fibrosis epithelial cells containing ΔF508-CFTR. J. Clin. Invest. 100:2457-2465.
12. Dalemans, W., et al. 1991. Altered chloride ion channel kinetics associated with the ΔF508 cystic fibrosis mutation. Nature. 354:526-528.
13. Haws, C.M., et al. 1996. ΔF508-CFTR channels: kinetics, activation by forskolin, and potentiation by xanthines. Am. J. Physiol. 270:C1544-C1555.
14. Drumm, M.L., et al. 1991. Chloride conductance expressed by ΔF508 and other mutant CFTRs in Xenopus oocytes. Science. 254:1797-1799.
15. Hwang, T.C., Wang, F., Yang, I.C., and Reenstra, W. W. 1997. Genistein potentiates wild-type and ΔF508-CFTR channel activity. Am. J. Physiol. 273:C988-C998.
16. Al-Nakkash, L., and Hwang, T.C. 1999. Activation of wild-type and ΔF508-CFTR by phosphodiesterase inhibitors through cAMP-dependent and -independent mechanisms. Pflügers Arch. 437:553-561.
17. - channel. Trends Pharmacol. Sci. 20:448-453.
18. Yang, H., et al. 2003. Nanomolar affinity small molecule correctors of defective ΔF508-CFTR chloride channel gating. J. Biol. Chem. 278:35079-35085.
19. Pedemonte, N., et al. 2005. Phenylglycine and sulfonamide correctors of defective ΔF508- and G551D-CFTR chloride channel gating. Mol. Pharmacol. 67:1797-1807.
20. Ma, T., et al. 2002. Thiazolidinone CFTR inhibitor identified by high-throughput screening blocks cholera toxin-induced intestinal fluid secretion. J. Clin. Invest. 110:1651-1658. doi:10.1172/JCI200216112.
21. Muanprasat, C., et al. 2004. Discovery of glycine hydrazide pore-occluding CFTR inhibitors: mechanism, structure-activity analysis, and in vivo efficacy. J. Gen. Physiol. 124:125-137.
22. Ma, T., et al. 2002. High-affinity activators of cystic fibrosis transmembrane conductance regulator (CFTR) chloride conductance identified by high-throughput screening. J Biol. Chem. 277:37235-37241.
23. Kozutsumi, Y., Segal, M., Normington, K., Gething, M.J., and Sambrook, J. 1988. The presence of malfolded proteins in the endoplasmic reticulum signals the induction of glucose-regulated proteins, Nature. 332:462-464.
24. Sharma, M., et al. 2004. Misfolding diverts CFTR from recycling to degradation: quality control at early endosomes. J. Cell Biol. 164:923-933.
25. Ward, C.L., and Kopito, R.R. 1994. Intracellular turnover of cystic fibrosis transmembrane conductance regulator. Inefficient processing and rapid degradation of wild-type and mutant proteins. J. Biol. Chem. 269:25710-25718.
26. Ostedgaard, L.S., Zeihet, B., and Welsh, M.J. 1999. Processing of CFTR bearing the P574H mutation differs from wild-type and ΔF508-CFTR. J. Cell Sci. 112:2091-2098.
27. Sheppard, D.N., Ostedgaard, L.S., Winter, M.C., and Welsh, M.J. 1995. Mechanism of dysfunction of two nucleotide binding domain mutations in cystic fibrosis transmembrane conductance regulator that are associated with pancreatic sufficiency. EMBO J. 14:876-883.
28. Van Craenenbroeck, K., et al. 2005. Folding efficiency is rate-limiting in dopamine D4 receptor biogenesis. J. Biol. Chem. 280:19350-19357.
29. Gregoty, RJ., et al. 1991. Maturation and function of cystic fibrosis transmembrane conductance regulator variants beating mutations in putative nucleotide-binding domains 1 and 2. Mol. Cell. Biol. 11:3886-3893.
30. Galietta, L.J., Haggle, P.M., and Verkman, A.S. 2001. Green fluorescent protein-based halide indicators with improved chloride and iodide affinities. FEBS Lett. 499:220-224.
31. Chen, E.Y., Bartlett, M.C., Loo, T.W., and Clarke, D.M. 2004. The ΔF508 mutation disrupts packing of the transmembrane segments of the cystic fibrosis transmembrane conductance regulator. J. Biol. Chem. 279:39620-39627
32. Johnson, L.G., et al. 1992. Efficiency of gene transfer for restoration of normal airway epithelial function in cystic fibrosis. Nat. Genet. 2:21-25.
33. Cohen, F.E., and Kelly, J.W. 2003. Therapeutic approaches to protein-misfolding diseases. Nature. 426:905-909.
34. Selkoe, D.J. 2004. Cell biology of protein misfolding: the examples of Alzheimer's and Parkinson's diseases [review]. Nat. Cell Biol. 3:1054-1056.
35. Galietta, L.J., et al. 2001. Novel CFTR chloride channel activators identified by screening of combinatorial libraries based on flavone and benzoquinolizinium lead compounds. J. Biol. Chem. 276:19723-19728.
36. Galietta, L.J., et al. 1998. An electrogenic amino acid transporter in the apical membrane of cultured human bronchial epithelial cells. Am. J. Physiol. 276:L917-L923.
37. Zhang, J.H., Chung, T.D., and Oldenburg, K.R. 1999. A simple statistical parameter for use in valuation and validation of high throughput screening assays. J. Biomol. Screen. 4:67-73.