| Hazard Information | Back Directory | [Uses]
JNK3 inhibitor-3 (compound 15g) is a selective, BBB permeable and orally active c-Jun N-terminal kinase 3 (JNK3) inhibitor. JNK3 inhibitor-3 has inhibitory activities to JNK1, JNK2 and JNK3 with IC50 values of 147.8, 44.0 and 4.1 nM, respectively. JNK3 inhibitor-3 significantly improves the memory in mouse dementia model. JNK3 inhibitor-3 can be used for the research of Alzheimer’s disease[1]. | [in vivo]
JNK3 inhibitor-3 (30 and 60 mg/kg; oral administration, once daily for 2 or 2.2 month) improves the memory of 3xTg mouse dementia model[1].
1.19 Pharmacokinetic Properties of JNK3 inhibitor-3 in Rats[1]. | Rats
IV 1 mg/kg | Rats
PO 3 mg/kg | | AUC (hr?ng/mL) | 1085.24 | 2806.77 | | Cmax (ng/mL) | | 1238.85 | | Tmax (hr) | | 0.67 | | T1/2 (hr) | 0.36 | 1.14 | | BA (%) | | 86.21 | |
| Animal Model: | Homozygous 3xTg and APPswe/PS1dE9 double-transgenic mice model of Alzheimer’s disease[1] | | Dosage: | 30 and 60 mg/kg | | Administration: | Oral administration; once daily for 2 or 2.2 month | | Result: | Induced no abnormal symptoms or weight changes, significantly enhanced the spontaneous alteration in APP/PS1 and doses of 30 and 60 mg/kg than that of vehicle group in Y-maze test and showed a significant difference compared to the 3xTg vehicle control in the passive avoidance test.
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| [IC 50]
JNK3: 4.1 nM (IC50); JNK2: 44 nM (IC50); JNK1: 147.8 nM (IC50) | [References]
[1] Jun J, et al. Discovery of novel imidazole chemotypes as isoform-selective JNK3 inhibitors for the treatment of Alzheimer's disease. Eur J Med Chem. 2023 Jan 5;245(Pt 1):114894. DOI:10.1016/j.ejmech.2022.114894 |
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