AAK1-IN-4 是一种具有高选择性、可透过血脑屏障以及口服活性的接头蛋白2相关激酶1 (adaptor protein-2-associated kinase 1, AAK1) 抑制剂 (AAK1IC50=4.6 nM, FiltKi=0.9 nM, cellIC50=8.6 nM)。AAK1-IN-4 具有研究神经性疼痛的潜力。

AAK1-IN-4 is a highly selective, CNS-penetrable, and orally active adaptor protein-2-associated kinase 1 (AAK1) inhibitor (AAK1 IC 50 of 4.6 nM, Filt K i of 0.9 nM, and cell IC 50 of 8.6 nM). AAK1-IN-4 has the potential for the research for neuropathic pain [1].

AAK1-IN-4 (compound 43) (0.5 μM, 0-10 min) has good cell potencies of 2.4 in liver microsomes, as well as good metabolic stability (value of 95, 95, 93 for human, rat, and mouse microsomes, respectively) and no issue with CYP inhibitions [1].

AAK1-IN-4 (3 mg/kg; p.o; single) can significantly reduce tactile allodynia with close to 80% inhibition of the pain response in the rat CCI-induced pain model [1]. AAK1-IN-4 (3 mg/kg; p.o; 0-7.5 hours) has good spinal cord penetration and spinal-cord-to-plasma-concentration ratios of 8.8 [1]. AAK1-IN-4 (1-10 mg/kg; p.o.; 0-24.5 hours) can significantly reduces mechanical allodynia with over 80% peak inhibition of the pain response achieved at an oral dose of 10 mg/kg, and over 60% peak inhibition of the pain response at 3 mg/kg [1]. Animal Model: Male Sprague-Dawley rats (chronic constriction injury, CCI) [1] Dosage: 3 mg/kg Administration: p.o, 0-7.5 hours Result: Significantly reduced tactile allodynia with close to 80% inhibition of the pain response, as well as showed good spinal cord penetration and spinal-cord-to-plasma-concentration ratios of 8.8. Animal Model: Male Sprague-Dawley rats (STZ-induced diabetic peripheral neuropathic pain, DPNP) [1] Dosage: 1-10 mg/kg Administration: p.o., 0-24.5 hours Result: Significantly reduced mechanical allodynia with over 80% peak inhibition of the pain response achieved at an oral dose of 10 mg/kg, and over 60% peak inhibition of the pain response at 3 mg/kg.

1815612-79-3

C20H28N4O3

372.46

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years