DCLK1-IN-1

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]。