Therapeutics: c-jun N-terminal kinase (JNK); caspase recruitment domain family member 11 (CARD11)

Mouse and patient sample studies suggest JNK inhibitors could help treat a subtype of diffuse large B-cell lymphoma (DLBCL). Gain-of-function mutations in CARD11 are associated with poor outcomes in the active B cell-like subtype of DLBCL (ABC-DLBCL). In transgenic mice, expression of a human gain-of-function CARD11 mutant increased JNK signaling in B cells compared with expression of human wild-type CARD11 and was lethal to all mice within six days of birth. Levels of activated JNK were higher in primary B cells from ABC-DLBCL patients than in B cells from patients with another DLBCL subtype. In the cells from ABC-DLBCL patients, a tool compound that inhibits JNK increased cell death compared with vehicle. Next steps could include testing therapeutic JNK inhibitors in ABC-DLBCL cells.

Xigen S.A. has XG-102, a JNK inhibitor, in Phase I and Phase III testing to treat inflammation, pain and stroke. Xigen and Auris Medical Holding AG also have the compound in Phase III testing to treat hearing loss. ...