AZD5069

Alias: AZD 5069; AZD-5069; AZD5069

Cat No.:V3257 Purity: ≥98%

COA Product Data Instructions for use SDS

AZD-5069 (AZD5069) is a novel and potent CXCR2 chemokine receptor antagonist with potential anticancer and antiinflammatory activities.

AZD5069 Chemical Structure CAS No.: 878385-84-3
Product category: CXCR

This product is for research use only, not for human use. We do not sell to patients.

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Citations by Top Journals: Nature, Cell, Science, etc.

Top Publications Citing lnvivochem Products

Nature 2021, 597(7874):119-125.

Cell 2020,183:1202-1218.e25.

Science Adv 2022: 8, eabm9427.

Nature 597, 119–125 (2021)

Cell Stem Cell 2020,26(6):845-861.e12.

Science Trans Med 2023,15(701):eadd7872.

STTT 2023,8(1):91.

Cell Reports 2023,42(4):112313

Science Trans Med 2023, 15: eadd7872.

Cancer Cell 2021,39(4):529-547.e7.

Cancer Discov 2022,12(4):1106-1127.

Immunity 2023,56(3):620-634.e11.

J Am Chem Soc 2022,144:21831-21836.

Cell 2020,183:1202-1218.e25.

Science Adv 2022:8,eabm9427.

Nature 2021,597(7874):119-125.

Cell 2020,183:1202-1218.e25.

PNAS Nexus 2022,1(3):pgac063.

ACS Nano 2023,17(10):9110-9125.

Biomaterial 2023 Sep16:302:122333.

Purity & Quality Control Documentation

Current batch：

Purity: ≥98%

COA

MSDS

Instructions

Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Clinical Trial Information
Biological Data

Product Description

AZD-5069 (AZD5069) is a novel and potent CXCR2 chemokine receptor antagonist with potential anticancer and antiinflammatory activities. The proliferation and progression of tumor cells are facilitated by the upregulation of the CXC chemokine receptor CXCR2 in a range of distinct tumor cell types. Reduced tumorigenesis and metastasis were the results of CXCR2 inhibition. At a pIC50 of 9.1, AZD-5069 prevents radiolabeled CXCL8 from binding to human CXCR2. In phase Ib/II studies, AZD5069, an antagonist of CXCR2, is presently being studied in combination with tremelimumab for patients with metastatic squamous cell carcinoma of the head and neck and advanced solid tumors. AZD-5069 has the potential to treat individuals suffering from COPD and other inflammatory diseases.

Biological Activity I Assay Protocols (From Reference)

Targets

¹²⁵I-IL-8-CXCR2

ln Vitro

In vitro activity: AZD-5069 is a novel and potent antagonist of CXCR2 chemokine receptor with potential anticancer and antiinflammatory activities. The proliferation and progression of tumor cells are facilitated by the upregulation of the CXC chemokine receptor CXCR2 in a range of distinct tumor cell types. Reduced tumorigenesis and metastasis were the results of CXCR2 inhibition. At a pIC50 of 9.1, AZD-5069 prevents radiolabeled CXCL8 from binding to human CXCR2. In phase Ib/II studies, AZD5069, an antagonist of CXCR2, is presently being studied in combination with tremelimumab for patients with metastatic squamous cell carcinoma of the head and neck and advanced solid tumors. AZD-5069 has the potential to treat individuals suffering from COPD and other inflammatory diseases.

ln Vivo

Rat Airway LPS Challenge Model: Oral dosing of AZD5069, AZD8309, or AZ10397767 or dexamethasone (5.8 μmol/kg) was administered to treatment groups of eight rats one hour prior to LPS challenge. 0.9% saline was given to the rats in group 1. Groups of rats were given 0.1 mg/ml LPS in either a saline (0.9%) or saline vehicle control. After being housed in perspex boxes for thirty minutes, the rats were exposed to an aerosol produced by two jet nebulizers running at a 12 l/min airflow rate. Four hours after the LPS challenge, the airway was lavaged with three aliquots of sterile PBS at room temperature, and the trachea was cannulated. For cell counting, an aliquot of lavage fluid was taken out. Using a Hema-Tek-2000 automatic slide stainer (Fisher Scientific Ltd, UK, Loughborough, UK), slides were stained with Wright-Giemsa stain, and 200 cells were usually counted under a microscope. The cells were divided into mononuclear, neutrophil, and eosinophil subtypes. Monocytes, macrophages, and lymphocytes were examples of mononuclear cells. To calculate the quantity of neutrophils, the cell count was expressed as a percentage of the total count. Each treatment group's average neutrophil count was calculated, and the result was given as the mean ± S.E.M. GraphPad InStat was used to compare the results between treatment groups using nonparametric statistics, Mann-Whitney, or Kruskal-Wallis methodology. Rats were put to sleep using isofluorane, and then the animals' abdominal vena cava was used to draw blood samples (0.5 and 2 ml). Subsequently, the animals were put to death intraperitoneally with 1.0 ml of pentobarbitone sodium. An Advia Haematology System (Siemens, London, UK) was used to determine the differential cell numbers in one set of blood samples. The remaining blood sample (2 ml) was centrifuged for 10 minutes at 4°C at 2800g. Following its removal, the plasma was kept in storage at -20°C until the compound concentration could be ascertained.

Enzyme Assay

AZD-5069 functions as a CXCR2 antagonist by preventing radiolabelled [125I]-IL-8 from binding to human CXCR2 receptors. It also prevents GROα-induced Ca2+ flux in human neutrophils that have been loaded with fluo-3 dye.

Cell Assay

In a humidified incubator at 37°C and 5% CO2, human embryonic kidney 293 (HEK293) cells expressing recombinant human CXCR2 or CXCR1 were grown to about 80% confluence in Dulbecco's modified Eagle’s medium–Glutamax medium (Life Technologies Ltd, Paisley, UK) containing 10% (v/v) fetal calf serum and 0.5 mg/ml geneticin. Accutase (Sigma-Aldrich Company Ltd., Dorset, UK) was used to extract cells from the flask after it had been at 37°C for three to five minutes.

Animal Protocol

p.o.

Rat Airway LPS Challenge Model.

References

[1]. AZD8797 is an allosteric non-competitive modulator of the human CX3CR1 receptor. Biochem J. 2016 Mar 1;473(5):641-9.

[2]. Pharmacological inhibition of the chemokine receptor CX3CR1 attenuates disease in a chronic-relapsing rat model for multiple sclerosis. Proc Natl Acad Sci U S A. 2014 Apr 8;111(14):5409-14.

[3]. Substituted 7-amino-5-thio-thiazolo[4,5-d]pyrimidines as potent and selective antagonists of the fractalkine receptor (CX3CR1). J Med Chem. 2013 Apr 25;56(8):3177-90.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Molecular Formula

C18H22F2N4O5S2

Molecular Weight

476.51

Exact Mass

476.1

Elemental Analysis

C, 45.37; H, 4.65; F, 7.97; N, 11.76; O, 16.79; S, 13.46

CAS #

878385-84-3

Related CAS #

878385-84-3

Appearance

White to off-white solid powder

SMILES

C[C@H]([C@H](CO)O)OC1=NC(=NC(=C1)NS(=O)(=O)N2CCC2)SCC3=C(C(=CC=C3)F)F

InChi Key

QZECRCLSIGFCIO-RISCZKNCSA-N

InChi Code

InChI=1S/C18H22F2N4O5S2/c1-11(14(26)9-25)29-16-8-15(23-31(27,28)24-6-3-7-24)21-18(22-16)30-10-12-4-2-5-13(19)17(12)20/h2,4-5,8,11,14,25-26H,3,6-7,9-10H2,1H3,(H,21,22,23)/t11-,14+/m1/s1

Chemical Name

N-[2-[(2,3-difluorophenyl)methylsulfanyl]-6-[(2R,3S)-3,4-dihydroxybutan-2-yl]oxypyrimidin-4-yl]azetidine-1-sulfonamide

Synonyms

AZD 5069; AZD-5069; AZD5069

HS Tariff Code

2934.99.9001

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)

Solubility Data

Solubility (In Vitro)

DMSO: 90~95 mg/mL (188.9~199.4 mM)

Water: N/A

Ethanol: ~19 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: 2.62 mg/mL (5.50 mM) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

Solubility in Formulation 2: ≥ 2.25 mg/mL (4.72 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 22.5 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.

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Solubility in Formulation 3: ≥ 2.25 mg/mL (4.72 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 22.5 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.

Solubility in Formulation 4: ≥ 2.25 mg/mL (4.72 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 22.5 mg/mL clear DMSO stock solution to 900 μL corn oil and mix evenly.

Solubility in Formulation 5: 5%DMSO + 40%PEG300 + 65%ddH2O: 8.0mg/ml (16.79mM)

Solubility in Formulation 6: 12.5 mg/mL (26.23 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

(Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.0986 mL	10.4930 mL	20.9859 mL
	5 mM	0.4197 mL	2.0986 mL	4.1972 mL
	10 mM	0.2099 mL	1.0493 mL	2.0986 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.

Calculator

Mass

Concentration

Volume

Molecular Weight*

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Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

Calculate the Mass of a compound required to prepare a solution of known volume and concentration
Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume

See Example

An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

Enter 350.26 in the Molecular Weight (MW) box
Enter 10 in the Concentration box and choose the correct unit (mM)
Enter 5 in the Volume box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Concentration (Start)

Volume (Start)

Concentration (End)

Volume (End)

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Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
Enter 25 into the Concentration (End) box and select the correct unit (mM)
Enter 25 into the Volume (End) box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

Molecular formula

Total molecular weight

g/mol

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Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Volume (to add to vial)

Mass (in vial)

Desired Reconstitution Concentration

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Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
Click the “Calculate” button
The answer appears in the Volume (to add to vial) box

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)

Dosage mg/kg

Average weight of animals g

Dosing volume per animal μL

Number of animals

Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)

% DMSO

% Tween 80

% ddH₂O

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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.

Note： (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.

Clinical Trial Information

NCT Number	Recruitment	interventions	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT02499328	Active Recruiting	Drug: AZD9150 Drug: AZD5069	Advanced Solid Tumors & Metastatic Squamous Cell Carcinoma of the Head and Neck	AstraZeneca	August 6, 2015	Phase 1 Phase 2
NCT01735240	Completed	Drug: AZD5069 Drug: Ketoconazole	Asthma Pharmacokinetics	AstraZeneca	December 2012	Phase 1
NCT01332903	Completed	Drug: [14C] AZD5069	Healthy	AstraZeneca	May 2011	Phase 1
NCT01704495	Completed	Drug: AZD5069 Drug: Placebo	Asthma	AstraZeneca	November 2012	Phase 2
NCT00953888	Completed	Drug: AZD5069 Drug: Placebo	Healthy	AstraZeneca	July 2009	Phase 1

Biological Data

AZD5069

Inhibition of [125I]CXCL8 binding HEK293 cell membranes expressing recombinant human CXCR2 (solid symbols) or CXCR1 (open symbols) receptors. Circles denote AZD5069, triangles denote AZD8309, and squares denote AZ10397767.J Pharmacol Exp Ther.2015 May;353(2):340-50.

AZD5069

Concentration response curves for CXCL1 (A), C5a (B),N-formyl-methionyl-leucyl-phenylalanine (C) and leukotriene B4 (LTB4) (D) stimulating CD11b expression on human neutrophils in blood in the presence and absence of AZD5069.J Pharmacol Exp Ther.2015 May;353(2):340-50.

AZD5069

Time dependence for displacement of [3H]AZD5069 (1 nM) with 10μM AZ10397767 from HEK membranes expressing human CXCR2. Data are expressed as the percentage of specific binding of AZD5069.J Pharmacol Exp Ther.2015 May;353(2):340-50.