GSK356278 是一种有效，选择性，具有口服活性和可透过血脑屏障的磷酸二酯酶 4 (PDE4) 抑制剂，对人 PDE4A，PDE4B 和 PDE4D 的 pIC₅₀ 值分别为 8.6、8.8 和 8.7。GSK356278 具有抗炎活性，并具有抗焦虑和增强认知的作用。

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.

Solid

PDE4A 8.6 (pIC50) PDE4B 8.8 (pIC50

GSK356278 competes with [H]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.
GSK356278 bounds to the HARBS in rats, mice, marmosets, and ferrets with pKis of 7.9, 7.8, 8.4, and 8.5, respectively.
GSK356278 inhibits LPS-induced release of TNF-α in human whole blood, with a pIC50 of 7.6. has not independently confirmed the accuracy of these methods. They are for reference only.

GSK356278 (0.003-30 mg/kg; p.o.) shows anti-inflammatory activity in rodents at exposures that does not induce pica feeding.
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.
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. 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).
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).

Room temperature in continental US; may vary elsewhere.

-20°C, stored under nitrogen In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)

[1]. Rutter AR, et, al. GSK356278, a potent, selective, brain-penetrant phosphodiesterase 4 inhibitor that demonstrates anxiolytic and cognition-enhancing effects without inducing side effects in preclinical species. J Pharmacol Exp Ther. 2014 Jul;350(1):153-6

In Vitro: DMSO : 2.5 mg/mL (5.69 mM; Need ultrasonic)配制储备液