Clofutriben

Clofutriben (ASP3662) is a selective, orally active and brain-penetrant 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor with K_i values of 5.3 nM (human), 2.6 nM (mouse), and 23 nM (rat). Clofutriben inhibits conversion of inactive glucocorticoids to active glucocorticoids, reducing intracellular glucocorticoid exposure. Clofutriben ameliorates neuropathic pain, and restores muscle pressure thresholds in rodent models, while lacking effects in inflammatory pain^[1][2]. In Vitro:Clofutriben (6-15 nM) potently and competitively inhibits human, mouse, and rat recombinant 11β-HSD1 with K_i values of 5.3 nM, 2.6 nM, and 23 nM respectively^[2].
Clofutriben (30 μM) does not inhibit human HEK293-EBNA cell-expressed 11β-HSD2 even at concentrations up to 30 μM^[2].
Clofutriben (0.03-10 μM; 30 min before Cortisone) concentration-dependently inhibits Cortisone (HY-17461)-to-Cortisol (HY-N0583) conversion in ex vivo rat prefrontal cortex and spinal cord tissue, with near-complete inhibition at 10 μM^[2]. In Vivo:Clofutriben (0.03-0.3 mg/kg; p.o.; single dose; 0.03-0.3 μg per animal; i.t.; single dose) dose-dependently ameliorates mechanical allodynia in rats, with an oral ED₅₀ of 0.087 mg/kg and a maximum improvement rate of 80% at 0.3 mg/kg^[2].
Clofutriben (0.1-1 mg/kg; p.o.; single dose) at 0.3 and 1 mg/kg significantly ameliorates thermal hyperalgesia in rats, with a maximum improvement rate of 61% at 1 mg/kg^[2].
Clofutriben (0.1-1 mg/kg; p.o.; single dose) at 0.3 and 1 mg/kg significantly ameliorates mechanical allodynia in STZ (HY-13753)-induced diabetic rats, with a maximum improvement rate of 52% at 1 mg/kg^[2].
Clofutriben (0.1-1 mg/kg; p.o.; single dose) dose-dependently restores muscle pressure thresholds in rats, with an ED₅₀ of 0.31 mg/kg and a maximum improvement rate of 82% at 1 mg/kg^[2].
Clofutriben (0.1-1 mg/kg; p.o.; single dose) at doses up to 1 mg/kg has no effect on hot-plate test latency and only a weak effect on tail pinch test latency, indicating minimal activity against acute pain^[2].
Clofutriben (0.3-3 mg/kg; p.o.; single dose) at doses up to 3 mg/kg does not impair motor coordination in healthy rats^[2].