Sobetirome and Sob-AM2 Administration via Subcutaneous Injection

Drugs were prepared to be injected subcutaneously at 5 μL/g body weight concentration. Drug stocks from sobetirome (molecular weight [MV] = 328 g/mol; Sigma; SML1900) and Sob-AM2 (MW = 341 g/mol)^{21 (link),23 (link),30 (link)} were prepared by dissolving sobetirome and Sob-AM2 at 1 mg/mL in a previously prepared vehicle, composed of distilled water, Kolliphor^® (Sigma; C5135), and 1-Methyl-2-pyrrolidinone (Sigma; 328634) in 8:1:1 proportion. Saline was used to dilute the 1 mg/mL drug stocks to the final concentrations of 0.2 mg/mL sobetirome and 0.06 mg/mL Sob-AM2 (corresponding to 1.0 and 0.3 mg/kg dose, respectively). Since treatment with Sob-AM2 results in approximately twofold more sobetirome content in the brain than treatment with its precursor drug sobetirome,¹⁸ the chosen doses were 1.0 and 0.3 mg/kg of sobetirome and Sob-AM2, respectively, to achieve similar content of sobetirome in the brain with both treatments.