PG01

SKU: orb1706800

Description

PG01 is a potent CFTR chloride channel potentiator effective against multiple CFTR mutants, including ΔF508, E193K, G970R, and G551D, with sub-micromolar affinity. It corrects gating defects by enhancing forskolin-stimulated chloride currents, making it a valuable research tool for in vitro cystic fibrosis studies and CFTR pharmacology investigations.

Research Area

Pharmacology & Drug Discovery

Key Properties

• CAS Number: 853138-65-5
• MW: 439.55
• Purity: 99.87%
• Formula: C₂₈H₂₉N₃O₂
• SMILES: CC(C)c1ccc(NC(=O)C(N(C)C(=O)Cc2c[nH]c3ccccc23)c2ccccc2)cc1
• Target: CFTR
• Solubility: DMSO:30 mg/mL (68.25 mM)

Bioactivity

• Target IC50:
  CFTR (G551D):1.94 μM(Kd)|G970R:0.45 μM(Kd)|E193K:0.22 μM(Kd)
• In Vivo:
  Microsome metabolism studies and rat pharmacokinetic analysis indicate that PG01 metabolizes significantly faster than SF-03. The pharmacokinetics of PG01 in rats were assessed through serial plasma concentration measurements following single bolus infusions (5 mg/kg), revealing that its pharmacokinetics adhere to a two-compartment model with elimination half-times of less than 5 minutes and 130 minutes, and a distribution volume of 4 L.
• In Vitro:
  PG01 induces significant currents in cells expressing either G551D- or G1349D-CFTR. While PG01 alone does not activate ∆F508-CFTR, it notably enhances ∆F508-CFTR Cl- current in the presence of Forskolin (0.5 and 2 μM). At a concentration of 100 nM, PG01 markedly increases channel activity, evidenced by frequent channel openings. The compound's effectiveness in activating G551D-CFTR, with an apparent Kd of 1 μM, is roughly 100 times greater than that of genistein, and its potency in activating G1349D-CFTR is superior, requiring only 40 nM. These currents are blocked by CFTRinh-172 and absent in nontransfected cells, indicating specificity for CFTR modulation.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

CFTR, F508del-CFTR, PG01, PG-01, PG 01, Phenylglycine-01

Compound Identifiers

PubChem CID

4695397