| Bioactivity | DN-1289 is an orally active and selective inhibitor of dual leucine zipper kinase (DLK; IC50=17 nM) and leucine zipper-bearing kinase (LZK; IC50=40 nM). DN-1289 results significant attenuation of optic nerve crush (ONC)-induced p-c-Jun in mice model. DN-1289 has excellent in vivo plasma half-life and blood-brain barrier permeability[1]. |
| Target | IC50: 17 nM (DLK), 40 nM (LZK) |
| Invitro | DN-1289 (化合物 14) (0.1, 0.3, 和 1 μM; 0-20 h) 可阻断神经生长因子 (NGF) 戒断诱导的背根节 (DRG) 神经元轴突变性[1]。DN-1289 (0.1, 0.3, 和 1 μM; 0-20 h) 抑制 NGF 戒断诱导的 DRG 神经元中的细胞凋亡蛋白酶激活[1]。 |
| In Vivo | DN-1289 (化合物 14) (100 mg/kg and 150 mg/kg; 腹腔注射; 每日一次, 共 10-15 天) 在小鼠模型中的耐受性良好[1]。DN-1289 (150 mg/kg; 口服给药; 每天 2 次, 共 10 天) 在视神经挤压 (ONC) 急性损伤模型中抑制 c-Jun磷酸化[1]。药代动力学分析[1]Species |
| Name | DN-1289 |
| Formula | C18H19F4N7O2 |
| Molar Mass | 441.38 |
| Transport | Room temperature in continental US; may vary elsewhere. |
| Storage | Please store the product under the recommended conditions in the Certificate of Analysis. |
| Reference | [1]. Craig RA 2nd, et al. Discovery of Potent and Selective Dual Leucine Zipper Kinase/Leucine Zipper-Bearing Kinase Inhibitors with Neuroprotective Properties in In Vitro and In Vivo Models of Amyotrophic Lateral Sclerosis. J Med Chem. 2022 Dec 22;65(24):16290-16312. |