SR-3306 is a potent and highly inhibitor of brain penetrant JNK.

H9c2 cells treated with H2O2/FeSO4 (100 μM) are ~40% viable, whereas the addition of SR-3306(500 nM) or SR3562(500 nM ) to cells treated with H2O2/FeSO4(100 μM) increases viability to ~90%, and the addition of 10 μM Tat-Sab peptide to cells treated with H2O2/FeSO4 (100 μM) increases viability to ~70% compared with 98% viability in untreated cells [2].

SR-3306 (10 mg/kg/day (s.c.) for 14 days) decreases d-amphetamine-induced circling by 87% compared to 6-hydroxydopamine (6-OHDA)-lesioned animals given vehicle. Steady-state brain levels of SR-3306 at day 14 are 347 nM, approximately 2-fold higher than the cell-based IC50. SR-3306 (10 mg/kg/day (s.c.) for 14 days) increases the number of tyrosine hydroxylase immunoreactive (TH+) neurons in the SNpc by 6-fold and reduces the loss of TH+ terminals in the striatum relative to the corresponding side of 6-OHDA-lesioned rats that receive only vehicle (p<0.05). Immunohistochemical staining for phospho-c-jun (p-c-jun) reveals that SR-3306 (10 mg/kg/day (s.c.) for 14 days) produces a 2.3-fold reduction in the number of immunoreactive neurons in the substantia nigra pars compacta (SNpc) relative to vehicle-treated rats. In lean mice, intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) administration of SR-3306 reduces food intake and body weight. SR11935 (i.p. and i.c.v.) treatment exerts similar anorectic effects as SR-3306, suggesting that JNK2 or JNK3 mediates this effect via pan-JNK inhibition. Furthermore, SR-3306 (daily i.p. injection, 7 days) prevents increases in food intake and weight gain in lean mice on a high-fat diet, and this injection paradigm reduces high-fat intake and obesity in diet-induced obese mice [1][3].