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| Targets |
5-lipoxygenase (5-LOX). PF-4191834 is a selective, non-redox, non-iron chelating competitive inhibitor of 5-lipoxygenase with a Ki of 10 nM. It shows no activity toward cyclooxygenase enzymes.
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| ln Vitro |
PF-4191834 (PF-04191834) prevents the synthesis of 5-LOX products 5-HETE, 5-oxo-ETE, LTB4, and LTE4 at concentrations up to 30 μM, but does not prevent the synthesis of 5-LOX products at estimated IC50 values between 100 and 190 nM. With an IC50 value of 130 nM and an IC80 value of 370 nM, PF-4191834 (PF-04191834) strongly inhibits COX-1/2 enzymes or 12- or 15-LOX enzymes[1]. It also exerts concentration-regulated inhibition of human 5-LOX.
PF-4191834 is a potent and selective 5-LOX inhibitor with an IC50 of 229 nM and an IC50 of 130 nM for human 5-LOX. It is a non-iron chelating and non-redox inhibitor. It shows no activity toward the cyclooxygenase enzymes. |
| ln Vivo |
PF-4191834 is an orally active 5-LOX inhibitor. It is effective in inflammation and pain. It exhibits good potency in enzyme- and cell-based assays, as well as in a rat model of acute inflammation.
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| Enzyme Assay |
5-LOX enzyme inhibition assays are performed using recombinant human 5-LOX enzyme. The enzyme is incubated with the substrate arachidonic acid in assay buffer (50 mM Tris-HCl pH 7.5, 2 mM CaCl2, 2 mM ATP). The reaction product 5-HETE is quantified by HPLC or by ELISA. PF-4191834 is serially diluted and added to the reaction mixture. IC50 and Ki values are determined by non-linear regression analysis. Each concentration is tested in duplicate. Iron chelation and redox activity are assessed using appropriate control assays.
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| Cell Assay |
Cellular 5-LOX inhibition is evaluated in cell lines expressing 5-LOX (e.g., mast cells, leukocytes). Cells are cultured in appropriate media and stimulated to produce leukotrienes (e.g., by calcium ionophore). PF-4191834 is added at various concentrations. Leukotriene B4 (LTB4) and cysteinyl leukotrienes (LTC4, LTD4, LTE4) levels in the culture supernatant are measured by ELISA. Cell viability is assessed using MTT or LDH assays. Each experiment includes known 5-LOX inhibitors as positive controls and vehicle controls.
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| Animal Protocol |
In vivo efficacy is evaluated in rat models of acute inflammation (e.g., carrageenan-induced paw edema) and pain. PF-4191834 is administered orally at doses determined by preclinical studies. Paw swelling is measured by plethysmometry. Pain responses are assessed by the paw pressure test or hot plate test. Inflammatory mediators (LTB4) are measured in paw tissue or exudates. Sample sizes typically range from 6-10 animals per group.
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| ADME/Pharmacokinetics |
Molecular Weight: 393.50. Formula: C22H23N3O2S. CAS No.: 1029317-21-2. Target: Lipoxygenase. Purity: Typically ≥98%. For research use only.
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| Toxicity/Toxicokinetics |
No comprehensive toxicology data are publicly available. As a 5-LOX inhibitor, potential adverse effects may include gastrointestinal disturbances and effects on leukotriene-mediated immune functions. Standard toxicity studies would include acute and subchronic toxicity in rodents, genotoxicity screening, and evaluation of effects on the gastrointestinal and immune systems. No clinical trials have been reported for this compound. The compound is intended for research use only.
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| References | |
| Additional Infomation |
PF-4191834 has been used in basic science research on asthma.
PF-4191834 is also known as PF-04191834. It is an orally active, non-iron chelating, and non-redox inhibitor of 5-LOX with a Ki of 10 nM. It is effective in inflammation and pain. No clinical trials or regulatory approvals have been reported. The compound is for research use only. |
| Molecular Formula |
C22H23N3O2S
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|---|---|
| Molecular Weight |
393.51
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| Exact Mass |
393.151
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| CAS # |
1029317-21-2
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| PubChem CID |
24986635
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| Appearance |
White to yellow solid powder
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| LogP |
4.921
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
28
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| Complexity |
532
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
DVNQWYLVSNPCJZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H23N3O2S/c1-25-20(9-12-24-25)16-5-7-18(8-6-16)28-19-4-2-3-17(15-19)22(21(23)26)10-13-27-14-11-22/h2-9,12,15H,10-11,13-14H2,1H3,(H2,23,26)
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| Chemical Name |
4-[3-[4-(2-methylpyrazol-3-yl)phenyl]sulfanylphenyl]oxane-4-carboxamide
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| Synonyms |
PF 04191834; PF04191834; PF-04191834
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| HS Tariff Code |
2934.99.9001
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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 : ~100 mg/mL (~254.13 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (6.35 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
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. Solubility in Formulation 2: ≥ 2.5 mg/mL (6.35 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 25.0 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 | 2.5412 mL | 12.7062 mL | 25.4123 mL | |
| 5 mM | 0.5082 mL | 2.5412 mL | 5.0825 mL | |
| 10 mM | 0.2541 mL | 1.2706 mL | 2.5412 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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