CC-401 hydrochloride is a potent inhibitor of all three forms of JNK with Ki of 25 to 50 nM. It exhibits at least 40-fold selectivity for JNK compared with other related kinases, including p38, extracellular signal-regulated kinase (ERK), inhibitor of κB kinase (IKK2), protein kinase C, Lck, and zeta-associated protein of 70 kDa (ZAP70).
- Competitively binds the ATP binding site in JNK.
- Inhibits phosphorylation of the N-terminal activation domain of the transcription factor c-Jun.
- Demonstrates specificity in vitro using osmotic stress of the HK-2 human tubular epithelial cell line.
- Inhibits sorbitol-induced phosphorylation of c-Jun in a dosage-dependent manner.
- Does not prevent sorbitol-induced phosphorylation of JNK, p38, or ERK induced by sorbitol.
- Provides specific JNK inhibition in cell-based assays at 1 to 5 μM.