Art. -Nr.: HY-19836

Zimlovisertib

(Synonyms: PF-06650833)

7 Cited Publications

Kundenbewertung

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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Reinheit: 99.94%
CAS. Nr.: 1817626-54-2
Formel: C₁₈H₂₀FN₃O₄
Molecular Weight:361.37

Speicherung:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 1 year , -20°C, 6 months

Zimlovisertib Chemical Structure

CAS. Nr.: 1817626-54-2

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Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biologische Aktivität
- Beschreibung
- IC₅₀ & Target
- In Vitro
- In Vivo
- Clinical Trial
Chemical Information
Publications (7)
Lösungsmittel & Löslichkeit
- In Vitro
- In Vivo
Reinheit & Dokumentation
Verweise
Help & FAQs
Classifications
Bioz

Biologische Aktivität

Beschreibung

IC₅₀ & Target^[1]

IRAK4

.2 nM (IC₅₀)

Alle IRAK Isoform-spezifische Produkte anzeigen :

In Vitro

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 K_m 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.

In Vivo

Zimlovisertib (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 Zimlovisertib in plasma are 2.1 nM, 7.7 nM, 19 nM and 150 nM free, respectively, at 2.5 hours after oral administration of Zimlovisertib at 0.3, 1, 3, and 30 mg/kg. The fraction unbound in rat plasma of Zimlovisertib is 0.3^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model:

Male Sprague-Dawley rats^[1]
Dosage:

0.1 mg/kg, 1 mg/kg, 3 mg/kg, 30 mg/kg
Administration:

Oral administration; for 2.5 hours
Result:

Significantly inhibited LPS-induced TNF-α in a dose dependent manner.

Clinical Trial

NCT Number	Sponsor	Condition	Start Date	Phase A549
NCT01329991	Plexxikon\|		2011-05	PHASE1

Chemical Information

CAS. Nr. 1817626-54-2
Appearance Solid
Molecular Weight 361.37
Formel C₁₈H₂₀FN₃O₄
Color Off-white to yellow
SMILES

NC(C1=C(OC)C=C2C(C=CN=C2OC[C@@H]3[C@H](CC)[C@H](F)C(N3)=O)=C1)=O
Synonyms

PF-06650833
Versand

Room temperature in continental US; may vary elsewhere.

Speicherung

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	1 year
	-20°C	6 months

Publications (7)

All RT-PCRIn Vivo Efficacy StudyELISAWBHistological Imaging/Staining

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Journal Impact Factor

Nature

Molecular definition of the endogenous Toll-like receptor signalling pathways. [Abstract]

2024 Jul;631(8021):635-644. PMID: 38961291
Nat Immunol

Genetic variants in UNC93B1 predispose to childhood-onset systemic lupus erythematosus. [Abstract]

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.
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

A Novel IRAK4 Inhibitor DW18134 Ameliorates Peritonitis and Inflammatory Bowel Disease. [Abstract]

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.
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

Protein-ligand binding kinetics are primarily controlled by the protein, not the ligand. [Abstract]

2026 May 22:2026.05.20.726507. PMID: 42239232

Lösungsmittel & Löslichkeit

In Vitro:

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)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

2.7672 mL

13.8362 mL

27.6725 mL

5 mM

0.5534 mL

2.7672 mL

5.5345 mL

10 mM

0.2767 mL

1.3836 mL

2.7672 mL

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.

Molaritätsrechner

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Konzentration Konzentration

Volumen Volumen

Molecular Weight Molecular Weight

Verdünnungsrechner

Konzentration _{(Stammlösung)} × Volumen _{(Stammlösung)} = Konzentration _{(Ziellösung)} × Volumen _{(Ziellösung)}

Konzentration _{(Stammlösung)} Konzentration _{(Stammlösung)}

Volumen _{(Stammlösung)} Volumen _{(Stammlösung)}

Konzentration _{(Ziellösung)} Konzentration _{(Ziellösung)}

Volumen _{(Ziellösung)} Volumen _{(Ziellösung)}

In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

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.

Protocol 1

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.

Protocol 2

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.

Protocol 3

Add each solvent one by one: 10% DMSO 90% Corn Oil

Solubility: ≥ 2.08 mg/mL (5.76 mM); Clear solution

This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Please enter your animal formula composition:

%
DMSO +

Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
%
+
+
%
Tween-80 + +
%
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

Reinheit & Dokumentation

Select Batch:

Reinheit: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (280 KB)
SDS (394 KB)
- English - EN (394 KB)
- Français - FR (394 KB)
- Deutsch - DE (394 KB)
- Norwegian - NO (394 KB)
- Español - ES (394 KB)
- Swedish - SV (394 KB)
- Italian - IT (394 KB)
- Korean - KR (394 KB)
- Portuguese - PT (394 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

Verweise

[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]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

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
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

Keywords

Zimlovisertib

7 Cited Publications

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Zimlovisertib

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Posttranslational Modification Library

Publications Citing Use of MedChemExpress (MCE) Zimlovisertib

Alle IRAK Isoform-spezifische Produkte anzeigen

Biologische Aktivität

Chemical Information

Publications (7)

Lösungsmittel & Löslichkeit

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

Zimlovisertib

Immunology/Inflammation Compound Library

Kinase Inhibitor Library

Clinical Compound Library

Drug Repurposing Compound Library

Anti-COVID-19 Compound Library

Orally Active Compound Library

Anti-Blood Cancer Compound Library

Rare Diseases Drug Library

Heterocyclic Compound Library

Highly Selective Inhibitors Library

Serine/Threonine Kinase Inhibitor Library

Anti-Hematopathy Compound Library

Bioactive Compound Library Max

Kinase Inhibitor Library Mini

MCE Bioactive Compound Library

Drug Repurposing Compound Library Plus

Clinical Compound Library Plus

Bioactive Compound Library

Protein Kinase Compound Library

High-Throughput Bioactive Compound Library

Anti-Rheumatic Arthritis Compound Library

Posttranslational Modification Library

Publications Citing Use of MedChemExpress (MCE) Zimlovisertib

Alle IRAK Isoform-spezifische Produkte anzeigen

Biologische Aktivität

Chemical Information

Publications (7)

Lösungsmittel & Löslichkeit

Reinheit & Dokumentation

Verweise

Help & FAQs

Complete Stock Solution Preparation Table

Zimlovisertib Related Classifications

HY-19836 Related Classifications