Uses
Tovinontrine (IMR-687) is a highly potent and selective phosphodiesterase-9 (PDE9) inhibitor specifically for the treatment of sickle cell disease. IC50s are 8.19 nM and 9.99 nM for PDE9A1 and PDE9A2, respectively[1].
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)[1].
| Animal Model: | HbSS-Townes mice on a 129/B6 background (10-12 weeks old) [1] |
| Dosage: | 30 mg/kg |
| Administration: | Dosed daily by gavage for 30 days |
| Result: | Resulted in fetal hemoglobin (HbF) induction, reduced hemolysis and reduced reticulocytosis. |
IC 50
PDE9A1: 8.19 nM (); PDE9A2: 9.99 nM (); PDE1A3: 88.4 nM (); PDE1B: 8.48 nM (); PDE1C: 12.2 nM (); PDE5A2: 81.9 nM ()
References
[1] James G McArthur, et al. A novel, highly potent and selective phosphodiesterase-9 inhibitor for the treatment of sickle cell disease. Haematologica. 2020 Mar;105(3):623-631. DOI:
10.3324/haematol.2018.213462
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