SR-3306

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

SR-3306 是一种高选择性、脑渗透性、有效的 JNK 抑制剂，对 JNK1、JNK2 和 JNK3 的 IC50 分别为 67、283 和 159 nM。

SR-3306 is a highly selective, brain penetrant, potent inhibitor of JNK with IC50 of 67, 283 and 159 nM for JNK1, JNK2 and JNK3, >100-fold selectivity over p38; shows cell-based IC50 of 216 nM, protects dopaminergic neurons against MPTP neurotoxicity in vitro and in vivo, achieves dopaminergic neuronal survival in the 6-OHDA model; also prevents ROS increases and mitochondrial dysfunction.

The effect of SR-3306 or Tat-Sab on cell viability in response to oxidative stress is measured by an MTT assay. H9c2 cells treated with 100 μM H2O2/FeSO4 are ~40% viable, whereas the addition of 500 nM SR-3306 or 500 nM SR3562 to cells treated with 100 μM H2O2/FeSO4 increases viability to ~90%, and the addition of 10 μM Tat-Sab peptide to cells treated with 100 μM H2O2/FeSO4 increases viability to ~70% compared with 98% viability in untreated cells. Similar results are found for primary human cardiomyocytes .

Administration of 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 the TH+ terminals in the striatum relative to the corresponding side of 6-OHDA-lesioned rats that receive only vehicle (p<0.05). In addition, 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, which is approximately 2-fold higher than the cell-based IC50 for this compound. Finally, 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 of 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. Moreover, i.p. and i.c.v. administrations of SR11935 exert similar anorectic effects as SR3306, which suggests JNK2 or JNK3 mediates aspect of the anorectic effect by pan-JNK inhibition. Furthermore, daily i.p. injection of SR-3306 (7 days) prevents the increases in food intake and weight gain in lean mice upon high-fat diet feeding, and this injection paradigm reduced high-fat intake and obesity in diet-induced obese (DIO) mice.

SR3306

MAPK/ERK Signaling

JNK

JNK

Neurological Disease

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1128096-91-2

490.5591

C28H26N8O

>98% (HPLC)

10 mM in DMSO

CC1=CC=C(C2=NN(C3=CC=C(NC4=NC=CC(C5=CC=CC(N6CCOCC6)=C5)=N4)C=C3)C=N2)C=N1

2-Pyrimidinamine, N-[4-[3-(6-methyl-3-pyridinyl)-1H-1,2,4-triazol-1-yl]phenyl]-4-[3-(4-morpholinyl)phenyl]-

(-20℃)

With Ice Pack

≥ 2 years