Zimlovisertib (Synonyms: PF-06650833)

Name: Zimlovisertib
Brand: MedChemExpress
SKU: HY-19836
Rating: 5.0 (6 reviews)

Cat. No.: HY-19836 Purity: 99.94%: Data Sheet
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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.

For research use only. We do not sell to patients.

CAS No. : 1817626-54-2

Size	Stock	Quantity
Solid + Solvent (Highly Recommended)
10 mM * 1 mL in DMSO ready for reconstitution	In-stock	Estimated Time of Arrival: December 31
Solution
10 mM * 1 mL in DMSO	In-stock	Estimated Time of Arrival: December 31
Solid
1 mg	In-stock	Estimated Time of Arrival: December 31
5 mg	In-stock	Estimated Time of Arrival: December 31
10 mg	In-stock	Estimated Time of Arrival: December 31
25 mg	In-stock	Estimated Time of Arrival: December 31
50 mg	In-stock	Estimated Time of Arrival: December 31
100 mg	In-stock	Estimated Time of Arrival: December 31
500 mg	In-stock	Estimated Time of Arrival: December 31
1 g	Get quote
5 g	Get quote

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Customer Review

Based on 6 publication(s) in Google Scholar

6 Publications Citing Use of MCE Zimlovisertib

RT-PCR

In Vivo Efficacy Study

ELISA

Histological Imaging/Staining

: 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.

: 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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Biological Activity
Purity & Documentation
References
Customer Review

Description

IC₅₀ & Target^[1]

IRAK4

.2 nM (IC₅₀)

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

Molecular Weight

361.37

Formula

C₁₈H₂₀FN₃O₄

CAS No.

1817626-54-2

Appearance

Solid

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

Shipping

Room temperature in continental US; may vary elsewhere.

Storage

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

Solvent & Solubility

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)

Preparing
Stock Solutions

Concentration Solvent Mass	1 mg	5 mg	10 mg

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

View the 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.

Molarity Calculator
Dilution Calculator

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

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

This equation is commonly abbreviated as: C₁V₁ = C₂V₂

Concentration _(start)

Volume _(start)

Concentration _(final)

Volume _(final)

In Vivo:

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.

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.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
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.
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.
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

mg/kg

Animal weight
(per animal)

Dosing volume
(per animal)

μL

Number of animals

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

Please enter your animal formula composition:

DMSO +

Tween-80 +

Saline

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

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).

Calculation results:

Working solution concentration: mg/mL

Method for preparing stock solution: mg drug dissolved in μL DMSO (Stock solution concentration: mg/mL).

The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).

Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.

If the continuous dosing period exceeds half a month, please choose this protocol carefully.

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.

Purity & Documentation

Purity: 99.94%

Select Batch:

Data Sheet (280 KB) SDS (394 KB)

COA (253 KB) LCMS (94 KB)

Handling Instructions (2659 KB)

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. [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

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

Zimlovisertib Related Classifications

Inflammation/Immunology

Help & FAQs

Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

Zimlovisertib1817626-54-2PF-06650833PF06650833PF 06650833IRAKInterleukin-1 receptor associated kinaseIL-1R associated kinaseInhibitorinhibitorinhibit

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Zimlovisertib (Synonyms: PF-06650833)

Customer Review

Zimlovisertib Related Antibodies

6 Publications Citing Use of MCE Zimlovisertib

Featured Recommendations

•Related Screening Libraries:

•Related Small Molecules:

•Related Proteins:

View All IRAK Isoform Specific Products:

Biological Activity

Purity & Documentation

References

Customer Review

Zimlovisertib Related Antibodies

Molarity Calculator

Dilution Calculator

Complete Stock Solution Preparation Table

Zimlovisertib Related Classifications

Keywords:

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