Tovinontrine (IMR-687) is a highly potent and selective phosphodiesterase-9 (PDE9) inhibitor specifically for the treatment of sickle cell disease. IC 50 s are 8.19 nM and 9.99 nM for PDE9A1 and PDE9A2, respectively In Vitro IMR-687 inhibits PDE9A with more than 800-fold greater potency than PDE1A3, PDE1B, PDE1C, PDE5A2, with IC 50 values of 88.4 μM, 8.48 μM, 12.2 μM, and 81.9 μM, respectively. IMR-687 (0.1-10 μM) treatment in erythroid K562 cells for 72 hours induces hemoglobin (HbF) in a dose-dependent manner. IMR-687 (0.03-10 μM) treatment for 6 hours in erythroid K562 cells increases cGMP in a dose-dependent manner. MCE has not independently confirmed the accuracy of these methods. They are for reference only. In Vivo IMR-687 (30 mg/kg/day; after 30 days of treatment) shows a greater than 3-fold in the percent of HbF + F-cells (8.4% in vehicle treated and 27.3% in IMR-687 treated) and a corresponding 2-fold decrease in sickled red blood cells (56.3% in vehicle treated and 24.4% in IMR-687 treated) . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: HbSS-Townes mice on a 129/B6 background (10-12 weeks old) Dosage: 30 mg/kg Administration: Dosed daily by gavage for 30 days Result: Resulted in fetal hemoglobin (HbF) induction, reduced hemolysis and reduced reticulocytosis. Form:Solid IC50& Target:PDE9A1 8.19 nM () PDE9A2 9.99 nM () PDE1A3 88.4 nM () PDE1B 8.48 nM () PDE1C 12.2 nM () PDE5A2 81.9 nM ()