TC ASK 10

TC ASK 10 (Compound 10) is a potent, selective and orally active apoptosis signal-regulating kinase 1 (ASK1) inhibitor with an IC50 of 14 nM. The inhibitory activities of TC ASK 10 towards other representative panel of kinases are less than 50%, except for ASK2 (IC50 of 0.51 μM)[1].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> MAPK/ERK Pathway >> MAP3K

ASK1:14 nM (IC50)

TC ASK 10 (Compound 10; 0-10 μM; 1 hour; INS-1 cells) treatment inhibits streptozotocin (STZ)-induced JNK in INS-1 pancreatic β cells from 0.3 μM. Phosphorylation of p38 is also inhibited in a dosedependent manner[1]. Western Blot Analysis[1] Cell Line: INS-1 cells Concentration: 0 μM, 0.3 μM, 1 μM, 3 μM, 10 μM Incubation Time: 1 hour Result: Was found to inhibit streptozotocin (STZ)-induced JNK in INS-1 pancreatic β cells from 0.3 μM. Phosphorylation of p38 was also inhibited in a dosedependent manner.

Pharmacokinetic profiles in rats are tested. TC ASK 10 (Compound 10•HCl; rat cassette doing at 0.1 mg/kg, iv and 1 mg/kg, po.) has a good oral bioavailability. The Cmax, Tmax and AUCpo,0-8h are 285.1 ng/mL, 1.67 h and 275.4 ng.h/mL, respectively for TC ASK 10[1].

[1]. Terao Y, et al. Design and biological evaluation of imidazo[1,2-a]pyridines as novel and potent ASK1 inhibitors. Bioorg Med Chem Lett. 2012 Dec 15;22(24):7326-9.