DCLK1-IN-1 is a highly selective inhibitor of DCLK1 and DCLK2 with IC50 values of 9.5nM and 31nM respectively in the KINOMEscan binding assay, and IC50 values of 57nM and 103nM respectively in the ATP kinase assay[1].
DCLK1-IN-1 potently binds DCLK1 in HCT116 cells with IC50 of 279nM[1]. DCLK1-IN-1(5μM and 10μM, 1h) mitigates NF-κB activation and inflammatory response in oxLDL-challenged macrophages[2].
DCLK1-IN-1(2mg/kg, i.v.) has a favorable pharmacokinetic profile in mice, with a half-life of 2.09h, an area under the curve of 5,506h·ng−1ml−1 and 81% oral bioavailability[1]. DCLK1-IN-1 had no discernable effect on thezebrafish central nervous system or rat hippocampal neurons[1]. DCLK1-IN-1(10mg/kg/2 days, 8 weeks, p.o.) prevents atherosclerotic progression and inflammation in mice[2].
References:
[1]. Ferguson F M, Nabet B, Raghavan S, et al. Discovery of a selective inhibitor of doublecortin like kinase 1[J]. Nature chemical biology, 2020, 16(6): 635-643.
[2]. Huang Z, Shen S, Han X, et al. Macrophage DCLK1 promotes atherosclerosis via binding to IKKβ and inducing inflammatory responses[J]. EMBO Molecular Medicine, 2023, 15(5): e17198.
DCLK1-IN-1是DCLK1和DCLK2的高选择性抑制剂，在KINOMEscan结合试验中对DCLK1和DCLK2的IC50分别为9.5nM和31nM。在ATP激酶实验中的IC50分别为57nM和103nM[1]。
DCLK1-IN-1可有效结合HCT116细胞中的DCLK1，IC50=279nM[1]。DCLK1-IN-1（5μM和10μM，1h）可减轻氧化低密度脂蛋白刺激的巨噬细胞中的NF-κB激活和炎症反应[2]。
DCLK1-IN-1（2mg/kg，i.v.）在小鼠中具有良好的药代动力学特征，半衰期为2.09h，曲线下面积为5,506h·ng−1ml−1，口服生物利用度为81%[1]。DCLK1-IN-1对斑马鱼中枢神经系统或大鼠海马神经元没有明显影响[1]。DCLK1-IN-1（10mg/kg/2 days；8 weeks；p.o.）可预防小鼠动脉粥样硬化进展和炎症[2]。