PG01 is effective on ΔF508 (Ka of 0.3 μM). PG01 is also an effective CFTR Cl- channel potentiator. PG01 increases ΔF508-CFTR Cl- current after adding Forskolin. PG01 can correct gating defects of CFTR mutants, is effective on b>E193K, G970R, and G551D (CFTR mutants) with Kd values of 0.22 μM, 0.45 μM and 1.94 μM, respectively.

PG01 produces large currents in both G551D- and G1349D-CFTR expressing cells. PG01 itself does not activate ?F508-CFTR, produces substantial ?F508-CFTR Cl- current after the addition of 0.5 and 2 μM Forskolin. PG01 (100 nM) strongly stimulates channel activity with multiple channel openings observed. The apparent Kd for 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. The currents are sensitive to CFTRinh-172 and are not seen in nontransfected cells[1].

Microsome metabolism studies and rat pharmacokinetic analysis suggest a significantly more rapid metabolism of PG01 than SF-03. 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 the volume of distribution 4 L [1].

853138-65-5

C28H29N3O2

439.55

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years