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Small molecule-facilitated anion transporters in cells for a novel cystic fibrosis therapeutic approach.

BACKGROUND AND PURPOSE: Cystic fibrosis (CF) is a lethal autosomal recessive genetic disease that originates from the defective function of the CFTR protein, a cAMP-dependent anion channel involved in fluid transport across epithelium. Due to their capability to replace the ion transport independently from the genetic mutation that affects the CFTR, small synthetic transmembrane anion transporters, named anionophores, are candidates as new potential CF therapeutics.

EXPERIMENTAL APPROACH: With the aim of evaluating their impact on cell physiology, we have analysed the transport properties of five compounds, three prodigiosines and two tambjamines.

KEY RESULTS: All studied compounds are capable of transporting halides and bicarbonate across the cell membrane, with a higher transport capacity at acidic pH. Interestingly, the presence of these anionophores do not interfere with the activation of CFTR, and do not modify the action of the lumacaftor and ivacaftor, a CFTR-corrector and -potentiator, respectively.

CONCLUSION AND IMPLICATIONS: Their ability to transport chloride and bicarbonate when applied at low concentration take shape as a promising starting point for the development of novel CF-therapy drug candidates.

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