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Pulmonary disease

Cystic fibrosis (CF)

Poly(ADP-ribose) polymerase-3 (PARP-3)

Cell culture and mouse studies suggest antagonizing PARP-3 could be useful for treating CF. In a cell culture screen for small molecules that improved the function of the ΔF508 variant of cystic fibrosis transmembrane conductance regulator (CFTR), a common cause of CF, the sea sponge-derived compound latonduine increased surface expression and function of CFTR compared with vehicle. In both
ex vivo murine intestinal tissue and an in vivo salivation assay, latonduine increased CFTR function compared with vehicle. Next steps include SAR studies to identify more potent and selective PARP-3 inhibitors.
Vertex Pharmaceuticals Inc.'s VX-809, a small molecule corrector of CFTR ΔF508, is in Phase II testing for CF.

SciBX 5(45); doi:10.1038/scibx.2012.1186
Published online Nov. 15, 2012

Patented; available for licensing

Carlile, G.W. et al. Chem. Biol.; published online Oct. 26, 2012;
Contact: Graeme W. Carlile, McGill University, Montreal, Quebec, Canada