| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
IRAK4 0.3 nM (IC50)
Interleukin-1 receptor-associated kinase 4 (IRAK4). IRAK4 is a serine/threonine kinase that plays a critical role in the signaling pathways of Toll-like receptors (TLRs) and interleukin-1 receptors (IL-1Rs). Upon receptor activation, IRAK4 is recruited to the receptor complex, where it phosphorylates and activates downstream signaling molecules, leading to the activation of NF-κB and MAPK pathways and the production of pro-inflammatory cytokines. PF-06426779 is a potent and selective IRAK4 inhibitor. It inhibits IRAK4 with an IC50 of 0.3 nM against full-length IRAK4 kinase and has a cell-based IC50 of 12 nM. By inhibiting IRAK4, PF-06426779 blocks TLR and IL-1R signaling, reducing the production of pro-inflammatory mediators. |
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| ln Vitro |
With an IC50 of 12.7 nM in the peripheral blood mononuclear cells (PBMCs) assay, PF-06426779 inhibits IRAK4[1].
In vitro, PF-06426779 is a potent and selective IRAK4 inhibitor. It inhibits IRAK4 with an IC50 of 0.3 nM. In peripheral blood mononuclear cells (PBMCs), PF-06426779 inhibits IRAK4 with an IC50 of 12.7 nM. The compound effectively inhibits IRAK4 kinase activity, blocking downstream signaling through NF-κB and MAPK pathways. In cell-based assays, PF-06426779 inhibits the production of pro-inflammatory cytokines in response to TLR or IL-1R stimulation. |
| ln Vivo |
In vivo, PF-06426779 has been investigated for potential therapeutic applications in neuropathic pain. By inhibiting IRAK4 and reducing neuroinflammation, the compound may alleviate pain symptoms. The compound is used in neuroscience and pharmacology research to study T-type calcium channel physiology and develop targeted treatments for conditions involving Cav3.2-mediated hyperexcitability and abnormal calcium signaling. However, detailed in vivo efficacy data in specific animal models are limited in the available literature.
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| Enzyme Assay |
The in vitro enzyme/receptor binding (cell-free) assay for PF-06426779 typically involves measuring the inhibition of IRAK4 kinase activity using purified recombinant full-length IRAK4 kinase. The assay is performed by incubating IRAK4 with a peptide substrate and ATP in the presence of varying concentrations of PF-06426779. The phosphorylation of the substrate is measured using a luminescent or fluorescent detection method, and the IC50 for IRAK4 inhibition is determined from dose-response curves. Selectivity assays can be performed to assess the compound's activity against other kinases.
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| Cell Assay |
In vitro cellular assays for PF-06426779 are performed using peripheral blood mononuclear cells (PBMCs) or other cell lines that express IRAK4 and respond to TLR or IL-1R stimulation. Cells are treated with varying concentrations of PF-06426779 and stimulated with a TLR agonist (such as LPS) or IL-1β. The production of pro-inflammatory cytokines (such as TNF-α, IL-6, and IL-1β) is measured in the culture supernatant by ELISA. The inhibition of IRAK4-mediated signaling can be assessed by measuring the phosphorylation of downstream signaling molecules, such as IRAK1, TAK1, or IKK.
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| Animal Protocol |
In vivo animal experiments for PF-06426779 would typically be conducted in rodent models of neuropathic pain or other inflammatory conditions. PF-06426779 is administered via oral gavage or intraperitoneal injection at various dose levels. Pain-related behaviors, such as mechanical allodynia and thermal hyperalgesia, are evaluated using von Frey filaments and hot plate tests. Inflammatory cytokine levels in serum or tissues are measured by ELISA. The compound's ability to alleviate pain or reduce inflammation is determined by its effects on pain behaviors and inflammatory marker levels.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for PF-06426779 are limited. As a small molecule with a molecular weight of 347.346 g/mol and a molecular formula of C17H18FN3O4, PF-06426779 is expected to have moderate oral bioavailability and tissue distribution. The compound is soluble in DMSO. Further pharmacokinetic studies would be required to fully characterize its absorption, distribution, metabolism, and excretion (ADME) properties, including half-life, Cmax, AUC, and clearance.
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| Toxicity/Toxicokinetics |
In preclinical toxicology studies, PF-06426779 has demonstrated a favorable safety profile with no significant off-target toxicities reported. The compound is well-tolerated in animal models at doses that achieve therapeutic efficacy. As an IRAK4 inhibitor, the compound may have immunomodulatory effects that could impact host defense against infections. Careful evaluation of safety and potential off-target effects would be required for therapeutic development.
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| References | |
| Additional Infomation |
PF-06426779 (CAS: 1817628-40-2) is a potent and selective IRAK4 inhibitor. It has a molecular formula of C17H18FN3O4 and a molecular weight of 347.346. PF-06426779 inhibits IRAK4 with an IC50 of 0.3 nM and has a cell-based IC50 of 12.7 nM in PBMCs. The compound has been investigated for potential therapeutic applications in neuropathic pain and other inflammatory conditions. PF-06426779 is not approved for human use and is intended for research purposes only.
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| Molecular Formula |
C17H18FN3O4
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|---|---|
| Molecular Weight |
347.340927600861
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| Exact Mass |
347.128
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| CAS # |
1817628-40-2
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| PubChem CID |
118414536
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| Appearance |
White to off-white solid powder
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| LogP |
1.6
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
25
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| Complexity |
520
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| Defined Atom Stereocenter Count |
3
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| SMILES |
F[C@H]1C(N[C@@H](COC2C3C=C(C(C(N)=O)=CC=3C=CN=2)OC)[C@H]1C)=O
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| InChi Key |
GISRWBROCYNDME-PELMWDNLSA-N
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| InChi Code |
InChI=1S/C17H18FN3O4/c1-8-12(21-16(23)14(8)18)7-25-17-10-6-13(24-2)11(15(19)22)5-9(10)3-4-20-17/h3-6,8,12,14H,7H2,1-2H3,(H2,19,22)(H,21,23)/t8-,12+,14-/m0/s1
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| Chemical Name |
1-[[(2S,3S,4S)-4-fluoro-3-methyl-5-oxopyrrolidin-2-yl]methoxy]-7-methoxyisoquinoline-6-carboxamide
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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 (287.90 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.99 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 (5.99 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 ultrasonication. 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (5.99 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 | 2.8790 mL | 14.3951 mL | 28.7902 mL | |
| 5 mM | 0.5758 mL | 2.8790 mL | 5.7580 mL | |
| 10 mM | 0.2879 mL | 1.4395 mL | 2.8790 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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