1. Metabolic Enzyme/Protease
  2. Phosphodiesterase (PDE)
  3. PF-04447943

PF-04447943 

Cat. No.: HY-15441 Purity: 99.97%
Handling Instructions

PF-04447943 is a potent inhibitor of human recombinant PDE9A (IC50=12 nM) with >78-fold selectivity, respectively, over other PDE family members (IC50>1000 nM).

For research use only. We do not sell to patients.

PF-04447943 Chemical Structure

PF-04447943 Chemical Structure

CAS No. : 1082744-20-4

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Free Sample (0.5-1 mg)   Apply Now  
Solution
10 mM * 1 mL in DMSO USD 176 In-stock
Estimated Time of Arrival: December 31
Solid + Solvent
10 mM * 1 mL
ready for reconstitution
USD 176 In-stock
Estimated Time of Arrival: December 31
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5 mg USD 160 In-stock
Estimated Time of Arrival: December 31
10 mg USD 290 In-stock
Estimated Time of Arrival: December 31
25 mg USD 610 In-stock
Estimated Time of Arrival: December 31
50 mg USD 990 In-stock
Estimated Time of Arrival: December 31
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Customer Review

Based on 4 publication(s) in Google Scholar

Top Publications Citing Use of Products

    PF-04447943 purchased from MCE. Usage Cited in: Acta Pharmacol Sin. 2017 Sep;38(9):1257-1268.

    C33(S) can alleviate cardiac hypertrophic responses in vitro. Cardiomyocytes are pre-incubated by C33(S) and PF-7943 for 1 h followed by PE treatment or not. The protein levels of fetal genes are measured. C33(500): C33(S) 500 nM, C33(50): C33(S) 50 nM, PF-7943(2): PF-7943 (2 μM).
    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    Description

    PF-04447943 is a potent inhibitor of human recombinant PDE9A (IC50=12 nM) with >78-fold selectivity, respectively, over other PDE family members (IC50>1000 nM).

    IC50 & Target

    IC50: 12 nM (PDE9A)[1]

    In Vitro

    Using recombinant human, rhesus, and rat PDE9A2 in a cell free assay PF-04447943 is shown to have a Ki of 2.8±0.26, 4.5±0.13, and 18.1±1.9 nM (n=4, 11 and 9 respectively). PF-04447943 is found to be highly selective over other PDE enzymes (PDE1, Ki=8600±2121 nM, n = 5; PDE2A3, Ki>99,000 nM; PDE3A, Ki>50,000 nM; PDE4A, Ki>29,000 nM; PDE5A, Ki=14,980±5025 nM, n=5; PDE6C, Ki=5324±2612 nM, n=4; PDE7A2, Ki>75,000 nM; PDE8A, Ki>50,000 nM; PDE10, Ki>51,250±20,056 nM, n=4; PDE11, Ki>80,000 nM) and no other significant activity at ~60 other receptors/enzymes. In HEK whole cells expressing rhesus PDE9A2, PF-04447943 inhibits ANP (0.3 μM) stimulated cGMP with an IC50 of 375±36.9 nM (n=16)[2].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    In Vivo

    Based on i.v. and p.o. dosing, pharmacokinetic studies with PF-04447943 in the rat indicates a Tmax of 0.3 h, T1/2 of 4.9 h, Cl of 21.7 mL/min/kg and an oral bioavailability of 47%. Thirty minutes following oral administration in rats (1-30 mg/kg), PF-04447943 concentrations dose-dependently increase in blood, brain and cerebrospinal fluid (CSF). The brain:plasma exposure ratios 30 min after dosing range from 0.13 at the 1 mg/kg dose to 0.33 at the 30 mg/kg dose. CSF levels are approximately 50% of brain levels. In mice, PF-04447943 (3, 10, 30 mg/kg p.o.) dose-dependently increases plasma and brain concentrations of PF-04447943 while the brain to plasma ratio ranged from 0.26 to 0.7 although this is not entirely dose dependent. CSF cGMP levels increase in a dose-dependent manner from a basal level of 3 pmol/mL to 13.3 pmol/mL (3.5-fold) at the 30 mg/kg dose. CSF cGMP levels also increase in a dose-dependent manner from a basal level of 3 pmol/mL in vehicle treated animals to 13.3 pmol/mL (3.5-fold) at the 30 mg/kg dose. CSF cGMP levels are elevated at all doses tested with a maximal effect of 3.5 fold increase above controls at 30 mg/kg[2].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Clinical Trial
    Molecular Weight

    395.46

    Formula

    C₂₀H₂₅N₇O₂

    CAS No.
    Shipping

    Room temperature in continental US; may vary elsewhere.

    Storage
    Powder -20°C 3 years
    4°C 2 years
    In solvent -80°C 6 months
    -20°C 1 month
    Solvent & Solubility
    In Vitro: 

    DMSO : ≥ 54.6 mg/mL (138.07 mM)

    *"≥" means soluble, but saturation unknown.

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.5287 mL 12.6435 mL 25.2870 mL
    5 mM 0.5057 mL 2.5287 mL 5.0574 mL
    10 mM 0.2529 mL 1.2644 mL 2.5287 mL
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 1.

      Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% saline

      Solubility: ≥ 2.5 mg/mL (6.32 mM); Clear solution

    • 2.

      Add each solvent one by one:  10% DMSO    90% (20% SBE-β-CD in saline)

      Solubility: ≥ 2.5 mg/mL (6.32 mM); Clear solution

    • 3.

      Add each solvent one by one:  10% DMSO    90% corn oil

      Solubility: ≥ 2.5 mg/mL (6.32 mM); Clear solution

    *All of the co-solvents are provided by MCE.
    References
    Cell Assay
    [2]

    The rhesus PDE9A2 construct is subcloned into a pcDNA3.3 TOPO vector and HEK 293 cells, stably transfected to constitutively express rhesus PDE9A2 and hNPR1, are incubated with PF-04447943 (30 μM to 1.5 nM) in assay media at a density of 10,000 cells/well, for 30 min at 37°C. Cyclic GMP formation is stimulated by incubation with 0.3 μM ANP (Atrial Natriuretic Peptide) for another 30 min at 37°C. Following incubation, cells are lysed with Antibody/Lysis buffer and ED Reagent for 1 h at room temperature. After a subsequent incubation with EA Reagent for 30 min at room temperature, followed by incubation with Substrate Reagent for 1 h at room temperature, cGMP concentrations are determined by measuring luminescence on the Envision Microplate Luminometer. The maximal inhibition (100% activity) in the cell based assay is determined using 30 μM PF-04447943 and 0% activity is defined by the DMSO control. PF-04447943 is titrated in quadruplicate, in a 10 point titration. Percentage inhibition is calculated using the maximal inhibition value and IC50 values are calculated from concentration response curves using Prism software[2].

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [2]

    Mice and Rats[2]
    For the mouse studies, male C57Bl/6J mice are administered PF-04447943 (3, 10, 30 mg/kg p.o.). For the rat studies rats (strain, weight range and supplier as described in the novel object recognition study below) are administered PF-04447943 10 mg/kg i.v. and p.o.. At various times after administration the animals are anesthetized with isoflurane; blood samples are withdrawn via cardiac puncture and placed in EDTA tubes on ice. Plasma is separated and frozen at -70°C until assayed for drug concentration. PF-04447943 and the internal standard are monitored in the positive ion mode at the transition from m/z 396.2 to 203.1 and m/z 477.3 to 266.2, respectively. Quantification is performed using Analyst 1.4 based on duplicate standard curves.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    References

    Purity: 99.97%

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