PF-04447943 | Selective PDE9A inhibitor

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PF-04447943 (1082744-20-4) is a potent (IC50 = 8.3 nM) and selective inhibitor of phosphodiesterase 9A (PDE9A) that increases cGMP levels and displays procognitive activity in mice.1,2 It displayed efficacy in the BACHD rat model of Huntington’s disease but not the Q175 mouse model.3 Also reduced the number and size of blood cell aggregates in patients with stable sickle cell disease.4 PF-04447943 attenuated DSS-induced colitis by suppressing oxidative stress, inflammation, and regulating T-cell polarization.5

References/CItations

  1. Verhoest et al. (2012), Design and discovery of 6-[(3S,4S)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (PF-04447943), a selective brain penetrant PDE9A inhibitor for the treatment of cognitive disorders; J. Med. Chem. 55 9045
  2. Hutson et al. (2011), The selective phosphodiesterase 9 (PDE9) inhibitor PF-04447943 (6-[(3S,4S)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one) enhances synaptic plasticity and cognitive function in rats; Neuropharmacology 61 665
  3. Nagy et al. (2015), Application of neurophysiological biomarkers for Huntington’s disease: evaluating a phosphodiesterase 9 inhibitor; Exp. Neurol. 263 122
  4. Charnigo et al. (2019), PF-04447943, A phosphodiesterase 9A Inhibitor, in Stable Sickle Cell Disease Patients: A Phase 1B Randomized, Placebo-Controlled Study; Clin. Transl. Sci. 12 180
  5. Rana et al. (2021), PDE9 Inhibitor PF-04447943 Attenuates DSS-Induced Colitis by Suppressing Oxidative Stress, Inflammation, and Regulating T-Cell Polarization; Front. Pharmacol. 12 643215
1082744-20-4, Edelinotrine supplier, PDE9A inhibitor, PF-04447943, PF-04447943 supplier, PF04447943, selective PDE9A inhibitor
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Edelinontrine

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Materials provided by Focus Biomolecules are for laboratory research use only and are not intended for human or veterinary applications. Please note that we do not sell to individuals and that all orders placed by non-research organizations will incur a $20 restocking/refund fee

PF-04447943 (1082744-20-4) is a potent (IC50 = 8.3 nM) and selective inhibitor of phosphodiesterase 9A (PDE9A) that increases cGMP levels and displays procognitive activity in mice.1,2 It displayed efficacy in the BACHD rat model of Huntington’s disease but not the Q175 mouse model.3 Also reduced the number and size of blood cell aggregates in patients with stable sickle cell disease.4 PF-04447943 attenuated DSS-induced colitis by suppressing oxidative stress, inflammation, and regulating T-cell polarization.5

References/CItations

  1. Verhoest et al. (2012), Design and discovery of 6-[(3S,4S)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one (PF-04447943), a selective brain penetrant PDE9A inhibitor for the treatment of cognitive disorders; J. Med. Chem. 55 9045
  2. Hutson et al. (2011), The selective phosphodiesterase 9 (PDE9) inhibitor PF-04447943 (6-[(3S,4S)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one) enhances synaptic plasticity and cognitive function in rats; Neuropharmacology 61 665
  3. Nagy et al. (2015), Application of neurophysiological biomarkers for Huntington’s disease: evaluating a phosphodiesterase 9 inhibitor; Exp. Neurol. 263 122
  4. Charnigo et al. (2019), PF-04447943, A phosphodiesterase 9A Inhibitor, in Stable Sickle Cell Disease Patients: A Phase 1B Randomized, Placebo-Controlled Study; Clin. Transl. Sci. 12 180
  5. Rana et al. (2021), PDE9 Inhibitor PF-04447943 Attenuates DSS-Induced Colitis by Suppressing Oxidative Stress, Inflammation, and Regulating T-Cell Polarization; Front. Pharmacol. 12 643215