Zimlovisertib
Based on 7 publication(s) in Google Scholar
Zimlovisertib (PF-06650833) 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. Zimlovisertib is used to treat diseases such as rheumatoid arthritis, lupus, and lymphomas.
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研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- 純度: 99.94%
- CAS 番号: 1817626-54-2
- 分子式: C18H20FN3O4
- 分子量:361.37
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保管条件:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 1 year , -20°C, 6 months
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- 純度とドキュメンテーション
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MedChemExpress（MCE）の使用を引用している文献 Zimlovisertib
More- Nature. 2024 Jul;631(8021):635-644. [Abstract]
- Nat Immunol. 2024 Jun;25(6):969-980. [Abstract]
- Cell Rep. 2024 Oct 8;43(10):114827. [Abstract]
- Inflammation. 2024 Sep 20. [Abstract]
- Molecules. 2024 Apr 16;29(8):1803. [Abstract]
- Exp Neurol. 2024 Jul:377:114794. [Abstract]
- bioRxiv. 2026 May 22:2026.05.20.726507. [Abstract]
Customer Validation & Images
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RT-PCR
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ELISA
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WB
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In Vivo Efficacy Study
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In Vivo Efficacy Study
生物活性
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IRAK4 .2 nM (IC50) |
The kinome selectivity profile of Zimlovisertib (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 Zimlovisertib 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, Zimlovisertib inhibits hERG current by 25% at 100 μM[1].
The ability of Zimlovisertib 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 Zimlovisertib, less than 5% inhibition of CYPs 1A2, 2C8, 2C9, 2D6, and 3A4 is observed. Lactam Zimlovisertib 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 Zimlovisertib, no time dependent CYP inhibition is observed. The potential induction of CYP3A by Zimlovisertib is assessed using cryopreserved human hepatocytes and afforded a 4.4-fold increase in mRNA at 10 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Male Sprague-Dawley rats[1]
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Dosage:0.1 mg/kg, 1 mg/kg, 3 mg/kg, 30 mg/kg
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Administration:Oral administration; for 2.5 hours
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Result:Significantly inhibited LPS-induced TNF-α in a dose dependent manner.
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
化学情報
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CAS 番号 1817626-54-2
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性状 Solid
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分子量 361.37
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分子式 C18H20FN3O4
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Color Off-white to yellow
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SMILES
NC(C1=C(OC)C=C2C(C=CN=C2OC[C@@H]3[C@H](CC)[C@H](F)C(N3)=O)=C1)=O
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別名
PF-06650833
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Powder -20°C 3 years 4°C 2 years In solvent -80°C 1 year -20°C 6 months
Publications (7)
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Journal Impact Factor
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Most Recent
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Nature
2024 Jul;631(8021):635-644. PMID: 38961291 -
Nat Immunol
2024 Jun;25(6):969-980. PMID: 38831104
Zimlovisertib purchased from MedChemExpress. Usage Cited in: Nat Immunol. 2024 Jun;25(6):969-980. [Abstract]
RT–qPCR analysis of IFIT1 and TNF expression in the indicated THP-1 cell lines, stimulated by R848 for 24 h after being incubated with Zimlovisertib (IRAK4 inh.; 0, 10, 20, 50 nM) for 30 min.
Zimlovisertib purchased from MedChemExpress. Usage Cited in: Nat Immunol. 2024 Jun;25(6):969-980. [Abstract]
Production of IL-6 and IL-8 in the supernatant of the indicated THP-1 cell lines, stimulated by R848 for 24 h after being incubated with Zimlovisertib (IRAK4 inh.; 0, 10, 20, 50 nM) for 30 min.
Zimlovisertib purchased from MedChemExpress. Usage Cited in: Nat Immunol. 2024 Jun;25(6):969-980. [Abstract]
Levels of phosphorylated NF-κB, ERK and P38, as measured by immunoblotting using lysates of the indicated THP-1 cells, stimulated by 1 μg /ml of R848 for 24 h after being incubated with Zimlovisertib (IRAK4 inh.; 0, 10, 20, 50 nM) for 30 min.
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Cell Rep
Polo-like kinase 2 promotes microglial activation via regulation of the HSP90α/IKKβ pathway. [Abstract]2024 Oct 8;43(10):114827. PMID: 39383034 -
Inflammation
Role for IRAK-4 and p38 in Neutrophil Signaling in Response to Bacterial Lipoproteins from Staphylococcus aureus. [Abstract]2024 Sep 20. PMID: 39302496 -
Molecules
2024 Apr 16;29(8):1803. PMID: 38675622
Zimlovisertib purchased from MedChemExpress. Usage Cited in: Molecules. 2024 Apr 16;29(8):1803. [Abstract]
Zimlovisertib (PF-06650833; 15, 30 mg/kg; PO; pretreated for 4 h) and then challenged with PBS or LPS (5 mg/kg) through i.p. administration for 2 hours in mice and the scores on behavior were observed.
Zimlovisertib purchased from MedChemExpress. Usage Cited in: Molecules. 2024 Apr 16;29(8):1803. [Abstract]
The levels of TNF- and IL-6 in the serum of mice with peritonitis were measured using ELISA Zimlovisertib (PF-06650833; 15, 30 mg/kg; PO; pretreated for 4 h) and then challenged with PBS or LPS (5 mg/kg) through i.p. administration for 2 hours in mice.
Zimlovisertib purchased from MedChemExpress. Usage Cited in: Molecules. 2024 Apr 16;29(8):1803. [Abstract]
Representative H&E-stained sections indicated the pathological damage in the colons, lungs. The arrows in Figure (Left) indicate inflammatory cell infiltration. The arrows in Figure (Right) indicate infiltrations around blood vessels and the alveolar cavit. Zimlovisertib (PF-06650833; 15, 30 mg/kg; PO; pretreated for 4 h) and then challenged with PBS or LPS (5 mg/kg) through i.p. administration for 2 hours in mice.
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Exp Neurol
Inhibiting the IRAK4/NF-κB/NLRP3 signaling pathway can reduce pyroptosis in hippocampal neurons and seizure episodes in epilepsy. [Abstract]2024 Jul:377:114794. PMID: 38685307 -
bioRxiv
2026 May 22:2026.05.20.726507. PMID: 42239232
溶剤 & 溶解度
DMSO : 62.5 mg/mL (172.95 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.08 mg/mL (5.76 mM); Clear solution
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.08 mg/mL (5.76 mM); Clear solution
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
純度とドキュメンテーション
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データシート (280 KB)
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SDS (394 KB)
- English - EN (394 KB)
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取扱説明書 (2659 KB)
参考文献
[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. [Content Brief]
[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. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 1 year; -20°C, 6 months. When stored at -80°C, please use it within 1 year. When stored at -20°C, please use it within 6 months.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
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| DMSO | 1 mM | 2.7672 mL | 13.8362 mL | 27.6725 mL | 69.1812 mL |
| 5 mM | 0.5534 mL | 2.7672 mL | 5.5345 mL | 13.8362 mL | |
| 10 mM | 0.2767 mL | 1.3836 mL | 2.7672 mL | 6.9181 mL | |
| 15 mM | 0.1845 mL | 0.9224 mL | 1.8448 mL | 4.6121 mL | |
| 20 mM | 0.1384 mL | 0.6918 mL | 1.3836 mL | 3.4591 mL | |
| 25 mM | 0.1107 mL | 0.5534 mL | 1.1069 mL | 2.7672 mL | |
| 30 mM | 0.0922 mL | 0.4612 mL | 0.9224 mL | 2.3060 mL | |
| 40 mM | 0.0692 mL | 0.3459 mL | 0.6918 mL | 1.7295 mL | |
| 50 mM | 0.0553 mL | 0.2767 mL | 0.5534 mL | 1.3836 mL | |
| 60 mM | 0.0461 mL | 0.2306 mL | 0.4612 mL | 1.1530 mL | |
| 80 mM | 0.0346 mL | 0.1730 mL | 0.3459 mL | 0.8648 mL | |
| 100 mM | 0.0277 mL | 0.1384 mL | 0.2767 mL | 0.6918 mL |
Zimlovisertib 関連分類
HY-19836 関連分類
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