PG01 is a potentCFTRCl^-channel potentiator. PG01 can correct gating defects ofCFTRmutants, is effective on b>E193K,G970RandG551D(CFTR mutants) withK_dvalues of 0.22 μM, 0.45 μM and 1.94 μM, respectively. PG01 is also effective onΔF508(K_aof 0.3 μM). PG01 increasesΔF508-CFTRCl^-current after adding Forskolin^[1][2].

CFTR^[1]

PG01 itself does not activate ?F508-CFTR, produces substantial ?F508-CFTR Cl^-current after the addition of 0.5 and 2 μM Forskolin. PG01 at 100 nM strongly stimulates channel activity with multiple channel openings observed. The apparent K_dfor PG01 for G551D-CFTR activation is 1 μM, approximately 100-fold better than that of genistein. The potency for activation G1349D-CFTR by PG01 is even better at 40 nM. PG01 produces large currents in both G551D- and G1349D-CFTR expressing cells. The currents are sensitive to CFTRinh-172 and are not seen in nontransfected cells^[1].

Pharmacokinetic analysis of PG01 in rats is done by serial measurements of plasma concentrations after single bolus infusions (5 mg/kg). PG01 pharmacokinetics fitted a two-compartment model with half-times of ＜5 min and 130 min with volume of distribution 4 L. Microsome metabolism studies and rat pharmacokinetic analysis suggests significantly more rapid metabolism of PG01 than SF-03^[1].

439.55

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C₂₈H₂₉N₃O₂

853138-65-5

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