AMG 487

Alias: AMG487; AMG-487; AMG 487

Cat No.:V2055 Purity: ≥98%

COA Product Data Instructions for use SDS

AMG-487 (AMG487) is a novel, potent, selective and oral antagonist of chemokine receptor 3CXCR3 with potential immunomodulatory and antiinflammatory activities.

AMG 487 Chemical Structure CAS No.: 473719-41-4
Product category: CXCR

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

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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
Biological Data

Product Description

AMG-487 (AMG487) is a novel, potent, selective and oral antagonist of chemokine receptor 3 CXCR3 with potential immunomodulatory and antiinflammatory activities. It has IC50s of 8.0 and 8.2 nM for I-IP-10 and I-ITAC, respectively, which inhibits the binding of CXCL10 and CXCL11 to CXCR3. I-IP-10 and I-ITAC, two chemokines, are prevented from binding to CXCR3 by AMG 487. AMG 487 has been shown in the cellular assays to inhibit CXCR3-mediated cell migration, with IC50 values for I-IP-10, I-ITAC, and MIG of 8 nM, 15 nM, and 36 nM, respectively.

Biological Activity I Assay Protocols (From Reference)

Targets

¹²⁵I-IP10-CXCR3 ( IC50 = 8 nM ); ¹²⁵I-ITAC-CXCR3 ( IC50 = 8.2 nM )

ln Vitro

AMG-487 (AMG487) suppresses the three CXCR3 chemokines' ability to migrate cells through CXCR3 (IP-10 IC50=8 nM, ITAC IC50=15 nM, and MIG IC50=36 nM). AMG 487 also suppresses the release of calcium in response to ITAC (IC50=5 nM)[1]. Reduced lung metastases and significantly smaller lungs compared to vehicle-treated lungs are observed with AMG487 (1 μM) treatment[2]. AMG487 stops C26 tumor cells from proliferating or surviving[3].

ln Vivo

AMG-487 (AMG487) (0.03-10 mg/kg, s.c.) significantly reduces cellular infiltration into the lungs in a dose dependent manner[1]. Compared to mice given a vehicle, AMG487 (5 mg/kg, s.c., twice daily) causes fewer metastases to form[2]. In both models, mice treated with AMG487 (5 mg/kg, s.c.) show fewer pulmonary nodules than the control group. AMG487 reduces the tumour volume[3].

Enzyme Assay

In order to examine the harmful impact of AMG487 on bone marrow cells and how it affects BMDC development, the bone marrow cells are exposed to AMG487 at concentrations of 3 μM, 15 μM, 30 μM, and 60 μM starting on day 0 and getting appropriate doses of AMG487 every three days. After two rounds of washing, LPS is added to the cells to promote maturation. We only add different concentrations of AMG487 (10 μM, 30 μM, and 60 μM) along with the LPS on day 6 in order to study its impact on BMDC activation. In every instance, the vehicle is added in equal parts as a control.

Cell Assay

At a density of 10⁴ cells cm², colon cancer cells are seeded and then incubated in serum-enriched medium or base medium (containing 0.1% bovine serum albumin, BSA) supplemented or not with different concentrations of rCXCL9, rCXCL10, and rCXCL11 for the indicated times. After that, they are either trypsin-detached, collected, and counted, or they are re-fed with fresh medium for three days, harvested, and counted. On day seven, photos are taken and the morphology of the CRC cells are examined using an inverted optical microscope at ×20 magnification.

Animal Protocol

Injection of 3×10⁵ viable tumor cells s.c. near the right abdominal mammary gland of syngeneic female mice is used to assess local tumor growth and spontaneous metastasis. Tumor diameters are measured twice a week using a caliper, and mice are put to death individually if their s.c. tumor measures 18 mm in diameter or earlier if they appear moribund. Under a dissecting microscope, surface tumor colonies are measured blindly while the lungs are removed and weighed. To assess experimental metastasis, 9×10⁴ viable tumor cells are injected intraperitoneally (i.v.) into the lateral tail vein of syngeneic female mice. On day 21 after transplantation, or earlier if the mice appeared moribund, all of the mice are put to death. Under a dissecting microscope, surface tumor colonies are measured blindly while the lungs are removed and weighed. A 50% hydroxypropyl-β-cyclodextrin solution is made; this solution acts as the vehicle at 20%. Following the addition of AMG487 to the 50% solution, the mixture is incubated for two hours in a sonicating water bath with periodic vortexing. To achieve the proper final concentration of AMG487 in 20% hydroxypropyl-β-cyclodextrin, distilled water is added.

References

[1]. Discovery and optimization of a series of quinazolinone-derived antagonists of CXCR3. Bioorg Med Chem Lett. 2007 Jun 15;17(12):3339-43.

[2]. Antagonism of CXCR3 inhibits lung metastasis in a murine model of metastatic breast cancer. Cancer Res. 2006 Aug 1;66(15):7701-7.

[3]. Organ-specific inhibition of metastatic colon carcinoma by CXCR3 antagonism. Br J Cancer. 2009 Jun 2;100(11):1755-64.

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

Physicochemical Properties

Molecular Formula	C32H28F3N5O4
Molecular Weight	603.591037750244
Exact Mass	603.21
Elemental Analysis	C, 63.68; H, 4.68; F, 9.44; N, 11.60; O, 10.60
CAS #	473719-41-4
Related CAS #	AMG 487 (S-enantiomer); 473720-30-8; (±)-AMG 487; 947536-03-0
Appearance	Solid powder
SMILES	CCOC1=CC=C(C=C1)N2C(=O)C3=C(N=CC=C3)N=C2[C@@H](C)N(CC4=CN=CC=C4)C(=O)CC5=CC=C(C=C5)OC(F)(F)F
InChi Key	WQTKNBPCJKRYPA-OAQYLSRUSA-N
InChi Code	InChI=1S/C32H28F3N5O4/c1-3-43-25-14-10-24(11-15-25)40-30(38-29-27(31(40)42)7-5-17-37-29)21(2)39(20-23-6-4-16-36-19-23)28(41)18-22-8-12-26(13-9-22)44-32(33,34)35/h4-17,19,21H,3,18,20H2,1-2H3/t21-/m1/s1
Chemical Name	N-[(1R)-1-[3-(4-ethoxyphenyl)-4-oxopyrido[2,3-d]pyrimidin-2-yl]ethyl]-N-(pyridin-3-ylmethyl)-2-[4-(trifluoromethoxy)phenyl]acetamide
Synonyms	AMG487; AMG-487; AMG 487
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: ~100 mg/mL (~165.7 mM) Ethanol: ~100 mg/mL
Solubility (In Vivo)	Solubility in Formulation 1: ≥ 2.5 mg/mL (4.14 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 25.0 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. Solubility in Formulation 2: 2.5 mg/mL (4.14 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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. View More Solubility in Formulation 3: ≥ 2.5 mg/mL (4.14 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.. Solubility in Formulation 4: 5%DMSO + 40%PEG300 + 5%Tween 80 + 50%ddH2O: 5.0mg/ml (8.28mM) Solubility in Formulation 5: 5 mg/mL (8.28 mM) in 20% HP-β-CD in Saline (add these co-solvents sequentially from left to right, and one by one), Suspened 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.)

Solubility (In Vitro)

DMSO: ~100 mg/mL (~165.7 mM)
Ethanol: ~100 mg/mL

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.14 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 25.0 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.

Solubility in Formulation 2: 2.5 mg/mL (4.14 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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.

View More

Solubility in Formulation 3: ≥ 2.5 mg/mL (4.14 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly..

Solubility in Formulation 4: 5%DMSO + 40%PEG300 + 5%Tween 80 + 50%ddH2O: 5.0mg/ml (8.28mM)

Solubility in Formulation 5: 5 mg/mL (8.28 mM) in 20% HP-β-CD in Saline (add these co-solvents sequentially from left to right, and one by one), Suspened 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	1.6568 mL	8.2838 mL	16.5675 mL
	5 mM	0.3314 mL	1.6568 mL	3.3135 mL
	10 mM	0.1657 mL	0.8284 mL	1.6568 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

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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
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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.

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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

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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.

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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
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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

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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.)

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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.

Biological Data

Curative effect of AMG487 on the development of pre-established colon cancer metastases. Br J Cancer . 2009 Jun 2;100(11):1755-64.
Inhibition of colon carcinoma metastases by preventive treatment with the antagonist AMG487. Br J Cancer . 2009 Jun 2;100(11):1755-64.
A-B, experimental lung metastases after tumor-specific or systemic blockade of CXCR3 with the antagonist AMG487. Cancer Res . 2006 Aug 1;66(15):7701-7.
A-B, local tumor growth and spontaneous lung metastasis after systemic treatment with AMG487Cancer Res . 2006 Aug 1;66(15):7701-7.