[CAS NO. 720704-34-7] GSK356278
PRODUCTS SPECIFICATIONS [720704-34-7]
DESCRIPTION [720704-34-7]
Overview
| MDL | MFCD27987927 |
|---|---|
| Molecular Weight | 439.53 |
| Molecular Formula | C21H25N7O2S |
| SMILES | CCN1C2=NC=C(C3=NN=C(CC4=C(C)N=C(C)S4)O3)C(NC5CCOCC5)=C2C=N1 |
Summary
GSK356278 is a potent, selective, orally bioavailable and brain-penetrant inhibitor of phosphodiesterase 4 (PDE4) , with pIC 50 s 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] .
IC50 & Target
|
PDE4A 8.6 (pIC 50 ) |
PDE4B 8.8 (pIC 50 ) |
PDE4D 8.7 (pIC 50 ) |
In Vitro
GSK356278 competes with [
3
H]rolipram for the high affinity rolipram binding site (HARBS) with a pK
i
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 pK
i
s 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 pIC
50
of 7.6
[1]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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 C
max
(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]
.
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| 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 ED 50 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%), C max (205 nM), T 1/2 (2.2 h). |
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date | Phase |
|---|---|---|---|---|
| NCT01031186 | GlaxoSmithKline |
Depressive Disorder and Anxiety Disorders
|
November 23, 2009 | Phase 1 |
| NCT01602900 | GlaxoSmithKline |
Huntington Disease
|
November 22, 2011 | Phase 1 |
| NCT01573819 | GlaxoSmithKline |
Huntington Disease
|
November 24, 2011 | Phase 1 |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
-20°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
Solvent & Solubility
DMSO : 2.5 mg/mL ( 5.69 mM ; Need ultrasonic)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 2.2752 mL | 11.3758 mL | 22.7516 mL |
| 5 mM | 0.4550 mL | 2.2752 mL | 4.5503 mL |
| 10 mM | --- | --- | --- |
