AAK1-IN-4 

AAK1-IN-4 is a highly selective, CNS-penetrable, and orally active adaptor protein-2-associated kinase 1 (AAK1) inhibitor (AAK1 IC₅₀ of 4.6 nM, Filt K_i of 0.9 nM, and cell IC₅₀ of 8.6 nM). AAK1-IN-4 has the potential for the research for neuropathic pain^[1].

IC₅₀: 4.6 nM (AAK1)^[1].
K_i: 0.9 nM (AAK1)^[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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

372.46

C₂₀H₂₈N₄O₃

1815612-79-3

CC(C[C@](N)(COC1=CC=C(C2=CC=NC(NC(OC)=O)=C2)N=C1C)C)C

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Luo G, et al. Discovery and Optimization of Biaryl Alkyl Ethers as a Novel Class of Highly Selective, CNS-Penetrable, and Orally Active Adaptor Protein-2-Associated Kinase 1 (AAK1) Inhibitors for the Potential Treatment of Neuropathic Pain. J Med Chem. 2022;65(6):4534-4564.  [Content Brief]