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| 5mg |
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| 25mg |
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Purity: ≥98%
PF-05180999 is a phosphodiesterase 2A (PDE2A) inhibitor, with an IC50 of 1.6 nM. PF-05180999 was identified as a preclinical candidate targeting cognitive impairment associated with schizophrenia. PF-05180999 demonstrated potent binding to PDE2A in brain tissue, dose responsive mouse brain cGMP increases, and reversal of N-methyl-d-aspartate (NMDA) antagonist-induced (MK-801, ketamine) effects in electrophysiology and working memory models in rats. Preclinical pharmacokinetics revealed unbound brain/unbound plasma levels approaching unity and good oral bioavailability resulting in an average concentration at steady state (Cav,ss) predicted human dose of 30 mg once daily (q.d.). Modeling of a modified release formulation suggested that 25 mg twice daily (b.i.d.) could maintain plasma levels of PF-05180999 at or above targeted efficacious plasma levels for 24 h, which became part of the human clinical plan.
| ln Vitro |
The phosphodiesterase 2A (PDE2A) inhibitor PF-05180999 has an IC50 of 1.6 nM. With Kis of 4.2, 8.4, and 5.5 nM and IC50 of 2.6, 5.2, and 3.4 nM, respectively, PF-05180999 binds to PDE2A in rats, dogs, and monkeys. With an IC50 of 2.03 μM (PDE10A1), 26.969 μM (PDE7B), 50.09 μM (PDE11A4), and >56.25 μM (PDE1B1, PDE3A1, PDE4D3, PDE5A1, PDE6 (bovine), PDE8B, and PDE9A1), respectively, PF-05180999 shows limited activity against PDEs. In addition to not directly inhibiting human recombinant cytochrome P450 (CYP) enzymes (1A2, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A), PF-05180999 is a modest inducer of CYP3A4 and does not stimulate CYP1A2 [1].
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| ln Vivo |
PF-05180999 (Compound 30; 0.032-0.32 mg/kg mg/kg, subcutaneous injection) significantly lowers ketamine-produced working memory mistakes in the rat radial arm maze (RAM) model of working memory. PF-05180999 induces an acute and exposure-dependent rise in the accumulation of global levels of cGMP in the cortex, striatum, and hippocampus, but without changes in cAMP and the related downstream phosphorylated cAMP response element binding protein (p-CREB). mice[1].
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| References |
[1]. Helal CJ, et al. Identification of a Potent, Highly Selective, and Brain Penetrant Phosphodiesterase 2A Inhibitor Clinical Candidate. J Med Chem. 2018 Feb 8;61(3):1001-1018
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| Molecular Formula |
C19H17F3N8
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|---|---|
| Molecular Weight |
414.387092351913
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| CAS # |
1394033-54-5
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| SMILES |
FC(C1=CN=C(C2=C(C3=C4C(N5CCC5)=NC=NN4C(C)=N3)C=NN2C)C=C1)(F)F
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| InChi Key |
CLGCHUKGBICQTE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C19H17F3N8/c1-11-27-15(17-18(29-6-3-7-29)24-10-26-30(11)17)13-9-25-28(2)16(13)14-5-4-12(8-23-14)19(20,21)22/h4-5,8-10H,3,6-7H2,1-2H3
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| Chemical Name |
4-(1-Azetidinyl)-7-methyl-5-[1-methyl-5-[5-(trifluoromethyl)-2-pyridinyl]-1H-pyrazol-4-yl]-imidazo[5,1-f][1,2,4]triazine
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| Synonyms |
PF 5180999; PF999; PF-999; PF 999; PF05180999; PF-05180999; PF 5180999; PF5180999; PF-5180999;
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~120.66 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.03 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.03 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.03 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.4132 mL | 12.0659 mL | 24.1319 mL | |
| 5 mM | 0.4826 mL | 2.4132 mL | 4.8264 mL | |
| 10 mM | 0.2413 mL | 1.2066 mL | 2.4132 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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