GSK3β inhibitor, ATP-competitive and selective
CAS：487021-52-3
分子式：C12H12N4O4S
分子量：308.31
纯度：98%
存储：Store at -20°C

Background:

IC50: 104 ± 27 nM

Glycogen synthase kinase 3 (GSK3) is a serine/threonine kinase that has been implicated in pathological conditions such as diabetes and Alzheimer’s disease (AD). AR-A014418 is a selective GSK-3 inhibitor.

In vitro: ARA014418 acted as an ATP-competitive manner and did not significantly inhibit cdk2 or cdk5 or 26 other kinases demonstrating high specificity for GSK3. AR-A014418 inhibited tau phosphorylation at a GSK3-specific site (Ser-396) in cells stably expressing human four-repeat tau protein [1].

In vivo: ARA014418 induced behavioural changes that were consistent with the effects of antidepressant drugs. Subacute intraperitoneal injections of AR-A014418 reduced immobility time in rats exposed to the forced swim test, which was a well-established model for antidepressant efficacy. Moreover, the specificity of this effect was supported by our finding that AR-A014418 decreased spontaneous as well as amphetamine-induced activity [2].

Clinical trial: currently no clinical data were available.

参考文献:
[1] Bhat R, Xue Y, Berg S, Hellberg S, Orm M, Nilsson Y, Rades ter AC, Jerning E, Markgren PO, Borgeg rd T, Nyl f M, Giménez-Cassina A, Hernández F, Lucas JJ, Díaz-Nido J, Avila J.  Structural insights and biological effects of glycogen synthase kinase 3-specific inhibitor AR-A014418. J Biol Chem. 2003;278(46):45937-45.
[2] Gould TD, Einat H, Bhat R, Manji HK.  AR-A014418, a selective GSK-3 inhibitor, produces antidepressant-like effects in the forced swim test. Int J Neuropsychopharmacol. 2004;7(4):387-90.