720704-34-7
720704-34-7 structure
- Name: GSK-356278
- Chemical Name: 5-[5-[(2,4-dimethyl-1,3-thiazol-5-yl)methyl]-1,3,4-oxadiazol-2-yl]-1-ethyl-N-(oxan-4-yl)pyrazolo[3,4-b]pyridin-4-amine
- CAS Number: 720704-34-7
- Molecular Formula: C21H25N7O2S
- Molecular Weight: 439.53400
- Catalog: Signaling Pathways Metabolic Enzyme/Protease Phosphodiesterase (PDE)
- Create Date: 2016-07-15 20:53:53
- Modify Date: 2024-01-14 09:19:14
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GSK356278 is a potent, selective, orally bioavailable and brain-penetrant inhibitor of phosphodiesterase 4 (PDE4), with pIC50s of 8.6, 8.8, and 8.7 for human PDE4A, PDE4B, and PDE4D, respectively. GSK356278 has anti-inflammatory activity, and exhibits anxiolytic and cognition-enhancing effects[1].
| Name | 5-[5-[(2,4-dimethyl-1,3-thiazol-5-yl)methyl]-1,3,4-oxadiazol-2-yl]-1-ethyl-N-(oxan-4-yl)pyrazolo[3,4-b]pyridin-4-amine |
|---|---|
| Synonyms | unii-1qta9p992c |
| Description | GSK356278 is a potent, selective, orally bioavailable and brain-penetrant inhibitor of phosphodiesterase 4 (PDE4), with pIC50s of 8.6, 8.8, and 8.7 for human PDE4A, PDE4B, and PDE4D, respectively. GSK356278 has anti-inflammatory activity, and exhibits anxiolytic and cognition-enhancing effects[1]. |
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| Related Catalog | |
| Target |
PDE4A:8.6 (pIC50) PDE4B:8.8 (pIC50) PDE4D:8.7 (pIC50) |
| In Vitro | GSK356278 competes with [3H]rolipram for the high affinity rolipram binding site (HARBS) with a pKi of 8.6 in a competitive filtration-binding assay to the recombinant human PDE4B2B enzyme expressed in yeast membranes[1]. GSK356278 bounds to the HARBS in rats, mice, marmosets, and ferrets with pKis of 7.9, 7.8, 8.4, and 8.5, respectively[1]. GSK356278 inhibits LPS-induced release of TNF-α in human whole blood, with a pIC50 of 7.6[1]. |
| In Vivo | GSK356278 (0.003-30 mg/kg; p.o.) shows anti-inflammatory activity in rodents at exposures that does not induce pica feeding[1]. GSK356278 (0.1-0.1 mg/kg; p.o.) demonstrates efficacy in a nonhuman primate model of anxiety at exposures that do not induce emesis[1]. GSK356278 (4 doses at 0.03, 0.1, 0.3, and 1.0 mg/kg for 6 weeks; p.o.) enhances performance in a nonhuman primate object retrieval test[1].GSK356278 exhibits oral bioavailability (rat 91%, monkey 23%) and Cmax (rat 205, monkey 41 nM) following oral administration (rat 1, monkey 0.2 mg/kg)[1]. GSK356278 exhibits terminal elimination half-lives (rat 2.2, monkey 1.5 h) due to moderate blood clearance (rat 40, monkey 16 mL/min/kg) combined with volumes of distribution (rat 6.3, monkey 2.1 L/kg) following intravenous administration (rat 1, monkey 0.2 mg/kg)[1]. Animal Model: Male Lewis rats (320-400 g) are treated with lipopolysaccharide (LPS)[1] Dosage: 0.003-3 mg/kg Administration: P.o. administration 30 minutes prior to the LPS challenge Result: Reduced the level of neutrophilia in a dose-dependent manner, with an ED50 of 0.09 mg/kg. Animal Model: Male CD rats[1] Dosage: 1 mg/kg (Pharmacokinetic Analysis) Administration: I.v. and p.o. administration Result: Oral bioavailability (91%), Cmax (205 nM), T1/2 (2.2 h). |
| References |
| Molecular Formula | C21H25N7O2S |
|---|---|
| Molecular Weight | 439.53400 |
| Exact Mass | 439.17900 |
| PSA | 132.02000 |
| LogP | 3.82920 |