PF06650833 (Synonyms: PF-06650833) |
Catalog No.GC19287
One-Click Copy Product Info
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PF06650833 (PF-06650833) est un inhibiteur puissant, sélectif et actif par voie orale de la kinase 4 associée au récepteur de l'interleukine-1 (IRAK4) avec des IC50 de 0,2 et 2,4 nM dans le test cellulaire et PBMC, respectivement.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1817626-54-2
Sample solution is provided at 25 µL, 10mM.
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PF06650833 is a potent, selective and orally active inhibitor of interleukin-1 receptor associated kinase 4 (IRAK4) with IC50s of 0.2 and 2.4 nM in the cell and PBMC assay, respectively. PF06650833 is used to treat diseases such as rheumatoid arthritis, lupus, and lymphomas[1][2].
The kinome selectivity profile of PF06650833 (Compound 40) is assessed in a panel of 278 kinases (Invitrogen) at 200 nM inhibitor concentration using the ATP Km for each kinase. Approximately 100% inhibition is observed for IRAK4[1]. Lactam PF06650833 (Compound 40) is assessed in a whole cell functional VEGF2R assay (PAE-KDR cell line). No activity is observed at concentrations up to and including 30 μM. In a voltage clamp assay, PF06650833 inhibits hERG current by 25% at 100 μM[1]. The ability of PF06650833 (Compound 40) to inhibit five major CYP450 enzymes is assessed using pooled human liver microsomes and probe substrates for the CYP450 enzymes. At a concentration of 3 μM of PF06650833, less than 5% inhibition of CYPs 1A2, 2C8, 2C9, 2D6, and 3A4 is observed. Lactam PF06650833 is examined for time dependent inhibition effects on six major CYP450 enzymes (CYP1A2, 2B6, 2C8, 2C9, 2C19, and 2D6) using pooled human liver microsomes and probe substrates. At 100 μM of PF06650833, no time dependent CYP inhibition is observed. The potential induction of CYP3A by PF06650833 is assessed using cryopreserved human hepatocytes and afforded a 4.4-fold increase in mRNA at 10 μM[1].
PF06650833 (Compound 40; 0.3-30 mg/kg; oral administration; for 2.5 hours; male Sprague-Dawley rats) treatment significantly inhibits LPS-induced TNF-α in a dose dependent manner. Mean exposures of PF06650833 in plasma are 2.1 nM, 7.7 nM, 19 nM and 150 nM free, respectively, at 2.5 hours after oral administration of PF06650833 at 0.3, 1, 3, and 30 mg/kg. The fraction unbound in rat plasma of PF06650833 is 0.3[1].
References:
[1]. Lee KL, et al. Discovery of Clinical Candidate 1-{[(2S,3S,4S)-3-Ethyl-4-fluoro-5-oxopyrrolidin-2-yl]methoxy}-7-methoxyisoquinoline-6-carboxamide (PF-06650833), a Potent, Selective Inhibitor of Interleukin-1 Receptor Associated Kinase 4 (IRAK4), by Fragment-Based Drug Design. J Med Chem. 2017 Jul 13;60(13):5521-5542.
[2]. Seganish WM. Inhibitors of interleukin-1 receptor-associated kinase 4 (IRAK4): a patent review (2012-2015). Expert Opin Ther Pat. 2016 Aug;26(8):917-32.
| Cas No. | 1817626-54-2 | SDF | |
| Synonymes | PF-06650833 | ||
| Canonical SMILES | NC(C1=C(OC)C=C2C(C=CN=C2OC[C@@H]3[C@H](CC)[C@H](F)C(N3)=O)=C1)=O | ||
| Formula | C18H20FN3O4 | M.Wt | 361.37 |
| Solubility | DMSO : ≥ 33 mg/mL (91.32 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.7672 mL | 13.8362 mL | 27.6725 mL |
| 5 mM | 553.4 μL | 2.7672 mL | 5.5345 mL |
| 10 mM | 276.7 μL | 1.3836 mL | 2.7672 mL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 40 reference(s) in Google Scholar.)