PF-04531083 (PF04531083) is a novel, potent and selective NaV1.8 blocker with the potential to be used for neuropathic/inflammatory pain. Voltage-gated sodium channels (Navs) are an important family of transmembrane ion channel proteins and Nav drug discovery is an exciting field. Pharmaceutical investment in Navs for pain therapeutics has expanded exponentially due to genetic data such as SCN10A mutations and an improved ability to establish an effective screen sequence for example IonWorks Barracuda®, Synchropatch® and Qube®. Moreover, emerging clinical data (AZD-3161, XEN402, CNV1014802, PF-05089771, PF-04531083) combined with recent breakthroughs in Nav structural biology pave the way for a future of fruitful prospective Nav drug discovery.
Physicochemical Properties
| Molecular Formula | C17H16CLN5O2 |
| Molecular Weight | 357.794241905212 |
| Exact Mass | 357.099 |
| CAS # | 1079400-07-9 |
| PubChem CID | 57582353 |
| Appearance | Light yellow to yellow solid powder |
| Density | 1.4±0.1 g/cm3 |
| Boiling Point | 471.0±45.0 °C at 760 mmHg |
| Flash Point | 238.7±28.7 °C |
| Vapour Pressure | 0.0±1.2 mmHg at 25°C |
| Index of Refraction | 1.670 |
| LogP | 1.61 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 25 |
| Complexity | 468 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | ZRJGMDIPCQOGNI-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C17H16ClN5O2/c1-23-14(7-8-20-23)17(24)22-15-6-4-11(16(19)21-15)12-9-10(25-2)3-5-13(12)18/h3-9H,1-2H3,(H3,19,21,22,24) |
| Chemical Name | N-[6-amino-5-(2-chloro-5-methoxyphenyl)pyridin-2-yl]-2-methylpyrazole-3-carboxamide |
| Synonyms | PF-04531083; PF04531083; PF 04531083 |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| References |
[1]. Recent progress in sodium channel modulators for pain. Bioorg Med Chem Lett. 2014 Aug 15;24(16):3690-9. |
| Additional Infomation |
Pf-04531083 has been investigated for the treatment of Pain and Chronic Pain. PF-04531083 is a small molecule NaV1.8 selective blocker developed by Pfizer. It has entered Phase I clinical trials for the treatment of neuropathic and inflammatory pain [1] It is administered orally [1] |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~279.49 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.81 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 20.8 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: ≥ 2.08 mg/mL (5.81 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 20.8 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. Solubility in Formulation 3: ≥ 2.08 mg/mL (5.81 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7949 mL | 13.9747 mL | 27.9494 mL | |
| 5 mM | 0.5590 mL | 2.7949 mL | 5.5899 mL | |
| 10 mM | 0.2795 mL | 1.3975 mL | 2.7949 mL |