N-(3-Cyano-4,5,6,7-tetrahydro-1-benzothien-2-yl)amides as potent, selective, inhibitors of JNK2 and JNK3

Inhibition of JNK2 and JNK3 by JNK inhibitor IX induces prometaphase arrest-dependent apoptotic cell death in human Jurkat T cells

“…Since JNKi is known to target JNK2 and JNK3 [14], these results suggest that the G 2 /M arrest occurred prior to the induction of mitochondrial damage and resultant apoptosis, and was provoked via a JNK2 and/or JNK3-governed mechanism insensitive to the anti-apoptotic effect of Bcl-2. Previous studies have shown that the phosphorylation of Bcl-2 family proteins, such as Bcl-2, Bcl-xL, Mcl-1, and Bim by Cdk1 couples the microtubule inhibitor-induced mitotic arrest to apoptotic cell death [17,[19][20][21].…”

“…In this study, in order to examine how cellular JNK inhibition by a validated JNK inhibitor (JNK inhibitor IX, JNKi), which acts as the ATP binding site-targeting inhibitor of JNK2 and JNK3 [14], cause apoptotic cell death, we investigated the apoptogenic mechanism of JNKi using human Jurkat T cell clone stably transfected with an empty vector (JT/Neo) or a Bcl-2 expression vector (JT/Bcl-2). In addition, to examine the dependency of JNKi-induced apoptotic events on G 2 /M arrest, the effect of aphidicolin (APC), which is known to arrest cell cycle progression at the G 1 /S boundary [15], on the JNKi-induced apoptotic events was investigated.…”

Metal Catalyzed Suzuki-Miyaura Cross-Coupling– Efficient Methodology for Synthesis the Natural and non-Natural biological active Molecules

“…From a chemistry perspective, several JNK selective inhibitors have started to emerge and include compounds from classes such as indazoles, aminopyrazoles, aminopyridines, pyridine carboxamides, benzothien-2-ylamides and benzothiazol-2-yl acetonitriles, [48] quinoline derivatives, and aminopyrimidines. Synthesis of final compound is described in Scheme 38.…”

The effects of short-term JNK inhibition on the survival and growth of aged sympathetic neurons

“…All were used at a final concentration of 10µM, and were included in the culture medium at the time of plating. The choice of concentration was informed by published information about their potency in cell-based assays, as well as precedent (Angell et al, 2007;Bennett et al, 2001;Gao et al, 2013;Holzberg et al, 2003;Salehi et al, 2006;Szczepankiewicz et al, 2006;Vivanco et al, 2007). With competitive inhibitors (e.g.…”