Home Metabolism PDE inhibitor GSK256066

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GSK256066 PDE inhibitor

Cat.No.S2620

GSK256066 is a selective PDE4B(equal affinity to isoforms A-D) inhibitor with IC50 of 3.2 pM, >380,000-fold selectivity versus PDE1/2/3/5/6 and >2500-fold selectivity against PDE4B versus PDE7. Phase 2.
GSK256066 PDE inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 518.58

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Quality Control

Batch: S262001 4-Methylpyridine]11 mg/mL]true]DMSO]Insoluble]false]Water]Insoluble]false Purity: 99.31%
99.31

Solubility

In vitro
Batch:

4-Methylpyridine : 11 mg/mL

DMSO : Insoluble
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Water : Insoluble

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In vivo
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Chemical Information, Storage & Stability

Molecular Weight 518.58 Formula

C27H26N4O5S

 Storage (From the date of receipt)
CAS No. 801312-28-7 Download SDF Storage of Stock Solutions

Synonyms N/A Smiles CC1=CC(=CC2=C(C(=CN=C12)C(=O)N)NC3=CC(=CC=C3)OC)S(=O)(=O)C4=CC=CC(=C4)C(=O)N(C)C

Mechanism of Action

Targets/IC50/Ki
PDE4B
3.2 pM
In vitro
GSK256066 is a slow and tight binding inhibitor of PDE4B with apparent IC50 of 3.2 pM. This compound is an extremely potent inhibitor of LPS-stimulated TNFα production in PBMCs with pIC50 of 11.0 and IC50 of 10 pM and human whole-blood cultures with pIC50 of 9.90 and IC50 of 126 pM. It is highly selective for PDE4 (>3.8 × 105-fold versus PDE1, PDE2, PDE3, PDE5, and PDE6 and >2.5 × 103-fold against PDE7). This chemical inhibits PDE4 isoforms A-D with equal affinity.
In vivo
GSK256066 inhibits 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. This compound inhibits the LPS-induced pulmonary neutrophilia with ED50 of 2.9 μg/kg, achieving maximal inhibition of 62% when given in the dry powder formulation. It 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. This chemical 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. It (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. This compound (0.3–100 μg/kg) inhibits LPS-induced increases in exhaled nitric oxide with ED50 of 35 μg/kg in rat. It (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. This chemical 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.
References

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT00612118 Completed
Allergic Rhinitis|Rhinitis Allergic Seasonal
GlaxoSmithKline
 February 2008 Phase 2
NCT00612820 Completed
Rhinitis Allergic Seasonal
GlaxoSmithKline
 January 2008 Phase 2
NCT00549744 Completed
Asthma
GlaxoSmithKline
 November 16 2007 Phase 2
NCT00549679 Completed
Pulmonary Disease Chronic Obstructive
GlaxoSmithKline
 October 4 2007 Phase 2
NCT00515268 Completed
Pulmonary Disease Chronic Obstructive
GlaxoSmithKline
 September 27 2007 Phase 1
NCT00464568 Completed
Rhinitis Allergic Seasonal
GlaxoSmithKline
 March 28 2007 Phase 2

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