GSK256066 - 10mM in DMSO , Phosphodiesterase 4 inhibitor, CAS No.801312-28-7, Phosphodiesterase 4 inhibitor

CAS: 801312-28-7 Cat. No.: G408704 Summenformel: C₂₇H₂₆N₄O₅S Molekulargewicht: 518.58 EG-Nummer: 629-882-0

GRADE & PURITY 10mM in DMSO

Synonyms

6-(3-(dimethylcarbamoyl)phenylsulfonyl)-4-(3-methoxyphenylamino)-8-methylquinoline-3-carboxamide

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Übersicht

Information

GSK256066 is a selectivePDE4B(equal affinity to isoforms A-D) inhibitor withIC50of 3.2 pM, >380,000-fold selectivity versus PDE1/2/3/5/6 and >2500-fold selectivity against PDE4B versus PDE7.Phase 2.
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 pIC50 of 11.0 and IC50 of 10 pM and human whole-blood cultures with pIC50 of 9.90 and IC50 of 126 pM. GSK256066 is highly selective for PDE4 (>3.8 × 10⁵-fold versus PDE1, PDE2, PDE3, PDE5, and PDE6 and >2.5 × 10³-fold against PDE7). GSK256066 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. GSK256066 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. 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.
Cell Data

cell lines：NR6, NR6M and NR6W cells

Concentrations：

Incubation Time：

Powder Purity:≥97%

Specifications

Synonyme

6-(3-(dimethylcarbamoyl)phenylsulfonyl)-4-(3-methoxyphenylamino)-8-methylquinoline-3-carboxamide

Spezifikationen & Reinheit

10mM in DMSO

Biochemische und physiologische Mechanismen

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.

Storage

Store at -80°C

Verschickt in

Dry ice packs + Cold packs

Dieses Produkt erfordert Kühlkettenversand. Grundversand und andere Economy-Optionen sind nicht verfügbar.

Aktionsart

INHIBITOR

Mechanismus der Wirkung

Phosphodiesterase 4 inhibitor

Namen und Kennungen

Isomere 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

Molekulargewicht

518.58

Reaxy-Rn

12158339

Reaxys-RN_link_address

https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=12158339&ln=

Chemische und physikalische Eigenschaften

• Löslichkeit: Solubility (25°C) In vitro DMSO: 74 mg/mL (199.83 mM)

Häufig gestellte Fragen

How should this product be stored?

Store at ?80 °C. Ultra-low temperature storage is required to maintain the specified shelf life.

How is this product shipped?

This product ships frozen with dry ice and cold packs. Unpack on arrival and transfer it to the storage condition stated above; handle dry ice with insulated gloves in a ventilated area.

What are the CAS number, molecular formula and molecular weight?

The CAS Number is 801312-28-7, the molecular formula is C27H26N4O5S, and the molecular weight is 518.58 g/mol.

What documentation is provided?

Available product documentation, including Certificates of Analysis (COA), Safety Data Sheets (SDS), and specification sheets, is shown in the product document area. Document availability and access follow the current site policy.