CP-628006 (CP628006) is a small molecule CFTR potentiator, potentiates low temperature-rescued F508del-CFTR with EC50 of 0.4 uM.
CP-628006 potentiated wild-type (EC50=24 nM), F508del-CFTR (EC500=400 nM), and G551D-CFTR (EC50=380 nM) by increasing the frequency and duration of channel openings in excised inside-out membrane patches assays.
CP-628006 efficaciously potentiated CFTR function in epithelia from cultured hBE cells. Its effects on the predominant CFTR variant F508del-CFTR were larger than those with the gating variant G551D-CFTR.
Combinations of CP-628006 and ivacaftor enhances the potentiation of G551D-CFTR, but not F508del-CFTR.
CP-628006 restores ATP-dependent channel gating to G551D-CFTR.
CP-628006 efficaciously potentiated the CFTR-mediated Cl− currents of plasma membrane-rescued F508del- and G551D-CFTR.
