IC50: 45 nM for JNK1 and 160 nM for JNK2 [1]
TCS JNK 6o is a ATP-competitive and selective c-Jun N-terminal kinase (JNK) inhibitor. JNKs belong to the mitogen-activated protein kinase (MAP kinase) family, and are responsive to stress stimuli, including ultraviolet irradiation, cytokines, osmotic shock and heat shock. JNKs also play a role in the cellular apoptosis and T cell differentiation pathway.
In vitro: CS JNK 6o, in a dose-dependent manner, inhibits phosphorylation of c-jun (EC50 = 920 nM) and prevents collagen-induced platelet aggregation. At low collagen concentrations (0.2 and 0.5 μg/ml), platelet aggregation was totally or partially impaired by 10 μM CS JNK 6o, whereas at a high collagen concentration (5 μg/ml), TCS JNK 6o had no effect [2].
In vivo:. Pharmacokinetic profiles were studied for TCS JNK 6o in Sprague-Dawley rats. TCS JNK 6o showed a short half-life of about 1 hour, with barely measurable bioavailability and rapid clearance. Microsomal incubation studies revealed that the oxidative metabolism of TCS JNK 6o was very rapid [1]
Clinical trial: So far, no clinical study has been conducted.
References:
[1] Szczepankiewicz BG1, Kosogof C, Nelson LT, Liu G, Liu B, Zhao H, Serby MD, Xin Z, Liu M, Gum RJ, Haasch DL, Wang S, Clampit JE, Johnson EF, Lubben TH, Stashko MA, Olejniczak ET, Sun C, Dorwin SA, Haskins K, Abad-Zapatero C, Fry EH, Hutchins CW, Sham HL, Rondinone CM, Trevillyan JM. Aminopyridine-based c-Jun N-terminal kinase inhibitors with cellular activity and minimal cross-kinase activity. J Med Chem. 2006 Jun 15;49(12):3563-80.
[2] Kauskot A, Adam F, Mazharian A, Ajzenberg N, Berrou E, Bonnefoy A, Rosa JP, Hoylaerts MF, Bryckaert M. Involvement of the mitogen-activated protein kinase c-Jun NH2-terminal kinase 1 in thrombus formation. J Biol Chem. 2007 Nov 2;282(44):31990-9.