GSK256066

SKU: orb1301115

Description

GSK256066

Research Area

Metabolism Research

Key Properties

• CAS Number: 801312-28-7
• MW: 518.58
• Purity: 99.60%
• Formula: C₂₇H₂₆N₄O₅S
• SMILES: N(C=1C2=C(C(C)=CC(S(=O)(=O)C3=CC(C(N(C)C)=O)=CC=C3)=C2)N=CC1C(N)=O)C4=CC(OC)=CC=C4
• Target: PDE
• Solubility: DMSO:10 mg/mL (19.28 mM)

Bioactivity

• Target IC50:
  PDE4B:3.2 pM
• In Vivo:
  GSK256066 inhibit the LPS-induced pulmonary neutrophilia with an ED50 of 1.1 μg/kg, achieving maximal Inhibition of 72% at 30 μg/kg when given in the aqueous suspension. GSK256066 inhibit the LPS-induced pulmonary neutrophilia with ED50 of 2.9 μg/kg, achieving maximal Inhibition of 62% when given in the dry powder formulation. GSK256066 shows a moderate plasma clearance of 39 mL/min/kg, a moderate volume of distribution of 0.8 L/kg, and a relatively short half-life of 1.1 hour in the Male CD rat. GSK256066 sustains at a high lung concentration of 2.6 μg/g after intra-tracheal administration as an aqueous suspension at a dose of 30 μg/kg in rats. GSK256066 (10 μg/kg) is administered intratracheally at different times (2, 6, 12, 18, 24, and 36 hours) before LPS administration, inhibiting LPS-Induced Pulmonary Neutrophilia in rat lipopolysaccharide (LPS)-induced models of acute pulmonary inflammation. GSK256066 (0.3–100 μg/kg) inhibits LPS-induced increases in exhaled nitric oxide with ED50 of 35 μg/kg in rat. GSK256066 (10 μg/kg) is administered half a hour before OVA administration in rat, inhibiting OVA-induced pulmonary eosinophilia with ED50 of 0.4 μg/kg. GSK256066 administered intratracheally as a dry powder blended in respiratory-grade lactose at doses of 3 to 100 μg/kg 2 hours before inhaled LPS challenge in ferrets, inhibiting LPS-induced pulmonary neutrophilia with ED50 of 18 μg/kg without inducing emetic episodes.
• In Vitro:
  GSK256066 is a slow and tight binding inhibitor of PDE4B with apparent IC50 of 3.2 pM. GSK256066 is an extremely potent inhibitor of LPS-stimulated TNFα production in PBMCs with IC50 of 11.0 and IC50 of 10 pM and human whole-blood cultures with IC50 of 9.90 and IC50 of 126 pM. GSK256066 is highly Selective for PDE4 (>3.8 x 105-fold versus PDE1, PDE2, PDE3, PDE5, and PDE6 and >2.5 x 103-fold against PDE7). GSK256066 inhibits PDE4 isoforms A-D with equal affinity.

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Disclaimer: For research use only

Alternative Names

GSK-256066, GSK 256066, GSK256066, Inhibitor, high-affinity, inhibit, obstructive, PDE4B, PDE, disease, chronic, Phosphodiesterase (PDE), phosphodiesterase, pulmonary

Compound Identifiers

PubChem CID

9827968