AMG-487 | CAS#473719-41-4 | CXCR3 antagonist

MedKoo Cat#: 206468 | Name: AMG-487

Description:

WARNING: This product is for research use only, not for human or veterinary use.

AMG 487 is a potent and selective antagonist of chemokine (C-X-C motif) receptor 3 (CXCR3) with IC50 values of 8nM and 8.2nM for I-IP-10 and I-ITAC, respectively. AMG 487 prevents the chemokines I-IP-10 and I-ITAC from binding to CXCR3. In the cellular assays, AMG 487 inhibits CXCR3-mediated cell migration with IC50 values of 8nM, 15nM and 36nM for I-IP-10, I-ITAC and MIG, respectively.

Chemical Structure

AMG-487

CAS#473719-41-4

Theoretical Analysis

MedKoo Cat#: 206468

Name: AMG-487

CAS#: 473719-41-4

Chemical Formula: C32H28F3N5O4

Exact Mass: 603.2093

Molecular Weight: 603.60

Elemental Analysis: C, 63.68; H, 4.68; F, 9.44; N, 11.60; O, 10.60

Price and Availability

Size	Price	Availability
5mg	USD 85.00	Ready to ship
10mg	USD 150.00	Ready to ship
25mg	USD 250.00	Ready to ship
50mg	USD 450.00	Ready to shipr
100mg	USD 750.00	Ready to ship
200mg	USD 1,350.00	Ready to ship
500mg	USD 2,950.00	Ready to ship

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Related CAS #

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Synonym

AMG-487; AMG 487; AMG487.

IUPAC/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

InChi Key

WQTKNBPCJKRYPA-UHFFFAOYSA-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

SMILES Code

CCOC1=CC=C(C=C1)N2C(=O)C3=C(N=CC=C3)N=C2C(C)N(CC4=CN=CC=C4)C(=O)CC5=CC=C(C=C5)OC(F)(F)F

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO, not in water

Shelf Life

>2 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.9001

More Info

Product Data

Product Data

Certificate of Analysis

View CoA: current batch, Lot#B21B03C19

QC Data

View QC data: current batch, Lot#B21B03C19

Safety Data Sheet (SDS)

View Safety Data Sheet (SDS)

Instruction

View handling instruction

Biological target:

AMG 487 is an orally active and selective antagonist of CXC chemokine receptor 3 (CXCR3) which inhibits the binding of CXCL10 and CXCL11 to CXCR3 with IC50s of 8.0 and 8.2 nM, respectively.

In vitro activity:

The effect of AMG 487 on dendritic cell (DC) biology and function was investigated. The expression of co-stimulatory markers on DCs was reduced, indicating the semi-mature state of DC when AMG 487 was added throughout the in vitro differentiation period. Additionally, when added solely during the final lipopolysaccharide-induced activation step, AMG 487 inhibited DC activation, as demonstrated by a decreased expression of activation markers. AMG487 also promoted the expression of PD-L2 and impaired the ability to induce antigen-specific T cell responses. Our results demonstrated that AMG 487 significantly affects DC maturity in vitro and function leading to impaired T cell activation, inducing DCs to have characteristics similar to tolerogenic DCs. AMG 487 may directly play an immunomodulatory role during DC development and functional shaping. Reference: Arch Immunol Ther Exp (Warsz). 2020 Apr 1;68(2):11. https://dx.doi.org/10.1007/s00005-020-00577-3

In vivo activity:

This study investigated the role of AMG487, a selective CXCR3 antagonist, in DBA/1J mice bearing collagen-induced arthritis (CIA). Following induction of CIA, animals were treated with 5 mg/kg AMG487 intraperitoneally every 48 h, starting from day 21 until day 41 and evaluated for clinical score, and histological hallmarks of arthritic inflammation. The effect of AMG487 on Th1 (T-bet), Th17 (IL-17A, RORγt, STAT3), Th22 (IL-22), and T regulatory (Treg; Foxp3 and IL-10) cells in splenic CXCR3+ and CD4+ T cells was investigated using flow cytometry. The effect of AMG487 on T-bet, RORγt, IL-17A, IL-22, Foxp3, and IL-10 at both mRNA and protein levels was assessed using RT-PCR and Western blot analyses of knee samples. The severity of clinical scores, and histological inflammatory damage decreased significantly in AMG487-treated compared with CIA control mice. Moreover, the percentage of Th1, Th17, and Th22 cells decreased significantly and that of Treg cells increased in AMG487-treated mice. It was further observed that AMG487-treatment downregulated T-bet, IL-17A, RORγt, and IL-22, whereas it upregulated Foxp3 and IL-10 mRNA and protein levels. This study demonstrates the antiarthritic effects of AMG487 in CIA animal model and supports the development of CXCR3 antagonists as a novel strategy for the treatment of inflammatory and arthritic conditions. Reference: Cell Signal. 2019 Dec;64:109395. https://linkinghub.elsevier.com/retrieve/pii/S0898-6568(19)30191-3

	Solvent	mg/mL	mM
Solubility
	DMSO	41.0	67.93

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 603.60 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

In vitro protocol:

1. Qin C, Liu H, Tang B, Cao M, Yu Z, Liu B, Liu W, Dong Y, Ren H. In Vitro Immunological Effects of CXCR3 Inhibitor AMG487 on Dendritic Cells. Arch Immunol Ther Exp (Warsz). 2020 Apr 1;68(2):11. doi: 10.1007/s00005-020-00577-3. PMID: 32239302. 2. Cambien B, Karimdjee BF, Richard-Fiardo P, Bziouech H, Barthel R, Millet MA, Martini V, Birnbaum D, Scoazec JY, Abello J, Al Saati T, Johnson MG, Sullivan TJ, Medina JC, Collins TL, Schmid-Alliana A, Schmid-Antomarchi H. Organ-specific inhibition of metastatic colon carcinoma by CXCR3 antagonism. Br J Cancer. 2009 Jun 2;100(11):1755-64. doi: 10.1038/sj.bjc.6605078. Epub 2009 May 12. PMID: 19436305; PMCID: PMC2695685.

In vivo protocol:

1. Bakheet SA, Ansari MA, Nadeem A, Attia SM, Alhoshani AR, Gul G, Al-Qahtani QH, Albekairi NA, Ibrahim KE, Ahmad SF. CXCR3 antagonist AMG487 suppresses rheumatoid arthritis pathogenesis and progression by shifting the Th17/Treg cell balance. Cell Signal. 2019 Dec;64:109395. doi: 10.1016/j.cellsig.2019.109395. Epub 2019 Aug 23. PMID: 31449849. 2. Cambien B, Karimdjee BF, Richard-Fiardo P, Bziouech H, Barthel R, Millet MA, Martini V, Birnbaum D, Scoazec JY, Abello J, Al Saati T, Johnson MG, Sullivan TJ, Medina JC, Collins TL, Schmid-Alliana A, Schmid-Antomarchi H. Organ-specific inhibition of metastatic colon carcinoma by CXCR3 antagonism. Br J Cancer. 2009 Jun 2;100(11):1755-64. doi: 10.1038/sj.bjc.6605078. Epub 2009 May 12. PMID: 19436305; PMCID: PMC2695685.

1: Zhang C, Deng Y, Zhang Y, Ba T, Niu S, Chen Y, Gao Y, Dai H. CXCR3 Inhibition Blocks the NF-κB Signaling Pathway by Elevating Autophagy to Ameliorate Lipopolysaccharide-Induced Intestinal Dysfunction in Mice. Cells. 2023 Jan 1;12(1):182. doi: 10.3390/cells12010182. PMID: 36611975; PMCID: PMC9818741. 2: Hua X, Zhang J, Ge S, Liu H, Du H, Niu Q, Chen X, Yang C, Zhang L, Liang C. CXCR3 antagonist AMG487 ameliorates experimental autoimmune prostatitis by diminishing Th1 cell differentiation and inhibiting macrophage M1 phenotypic activation. Prostate. 2022 Sep;82(13):1223-1236. doi: 10.1002/pros.24395. Epub 2022 Jun 14. PMID: 35700340. 3: Lari S, Hiyari S, de Araújo Silva DN, de Brito Bezerra B, Ishii M, Monajemzadeh S, Cui ZK, Tetradis S, Lee M, Pirih FQ. Local delivery of a CXCR3 antagonist decreases the progression of bone resorption induced by LPS injection in a murine model. Clin Oral Investig. 2022 Aug;26(8):5163-5169. doi: 10.1007/s00784-022-04484-z. Epub 2022 Apr 25. PMID: 35462591; PMCID: PMC9710470. 4: Liu J, Yao L, Huang S, Wang B, Li L, Li L, Gu W, Xiao S, Liu G. AMG487 inhibits PRRSV replication and ameliorates lung injury in pig lung xenografts by down-regulating the expression of ANXA2. Antiviral Res. 2022 Jun;202:105314. doi: 10.1016/j.antiviral.2022.105314. Epub 2022 Apr 8. PMID: 35405171. 5: Chen X, He H, Xiao Y, Hasim A, Yuan J, Ye M, Li X, Hao Y, Guo X. CXCL10 Produced by HPV-Positive Cervical Cancer Cells Stimulates Exosomal PDL1 Expression by Fibroblasts via CXCR3 and JAK-STAT Pathways. Front Oncol. 2021 Aug 6;11:629350. doi: 10.3389/fonc.2021.629350. PMID: 34422627; PMCID: PMC8377428. 6: Petrisko TJ, Konat GW. Peripheral viral challenge increases c-fos level in cerebral neurons. Metab Brain Dis. 2021 Oct;36(7):1995-2002. doi: 10.1007/s11011-021-00819-z. Epub 2021 Aug 18. PMID: 34406561. 7: Xiu W, Luo J. CXCL9 secreted by tumor-associated dendritic cells up-regulates PD-L1 expression in bladder cancer cells by activating the CXCR3 signaling. BMC Immunol. 2021 Jan 6;22(1):3. doi: 10.1186/s12865-020-00396-3. Erratum in: BMC Immunol. 2021 Feb 25;22(1):18. PMID: 33407095; PMCID: PMC7789583. 8: Sun R, Jang JH, Lauzon AM, Martin JG. Interferon-γ amplifies airway smooth muscle-mediated CD4+ T cell recruitment by promoting the secretion of C-X-C- motif chemokine receptor 3 ligands. FASEB J. 2021 Jan;35(1):e21228. doi: 10.1096/fj.202001480R. PMID: 33337555. 9: Qin J, Li A, Huang Y, Teng RH, Yang Y, Yao YX. CXCR3 contributes to neuropathic pain via ERK activation in the anterior cingulate cortex. Biochem Biophys Res Commun. 2020 Oct 15;531(2):166-171. doi: 10.1016/j.bbrc.2020.07.104. Epub 2020 Aug 8. PMID: 32782146. 10: Phan QT, Tan WH, Liu R, Sundaram S, Buettner A, Kneitz S, Cheong B, Vyas H, Mathavan S, Schartl M, Winkler C. Cxcl9l and Cxcr3.2 regulate recruitment of osteoclast progenitors to bone matrix in a medaka osteoporosis model. Proc Natl Acad Sci U S A. 2020 Aug 11;117(32):19276-19286. doi: 10.1073/pnas.2006093117. Epub 2020 Jul 27. PMID: 32719141; PMCID: PMC7431079. 11: Li LX, Xia YT, Sun XY, Li LR, Yao L, Ali MI, Gu W, Zhang JP, Liu J, Huang SG, Dai HC, Liu GQ. CXCL-10/CXCR3 in macrophages regulates tissue repair by controlling the expression of Arg1, VEGFa and TNFα. J Biol Regul Homeost Agents. 2020 May-Jun;34(3):987-999. doi: 10.23812/20-59-A-65. PMID: 32660198. 12: Bakheet SA, Alrwashied BS, Ansari MA, Nadeem A, Attia SM, Alanazi MM, Aldossari AA, Assiri MA, Mahmood HM, Al-Mazroua HA, Ahmad SF. CXC chemokine receptor 3 antagonist AMG487 shows potent anti-arthritic effects on collagen- induced arthritis by modifying B cell inflammatory profile. Immunol Lett. 2020 Sep;225:74-81. doi: 10.1016/j.imlet.2020.06.014. Epub 2020 Jun 23. PMID: 32590119. 13: Bakheet SA, Alrwashied BS, Ansari MA, Nadeem A, Attia SM, Assiri MA, Alqahtani F, Ibrahim KE, Ahmad SF. CXCR3 antagonist AMG487 inhibits glucocorticoid-induced tumor necrosis factor-receptor-related protein and inflammatory mediators in CD45 expressing cells in collagen-induced arthritis mouse model. Int Immunopharmacol. 2020 Jul;84:106494. doi: 10.1016/j.intimp.2020.106494. Epub 2020 Apr 15. PMID: 32304993. 14: Petrisko TJ, Bloemer J, Pinky PD, Srinivas S, Heslin RT, Du Y, Setti SE, Hong H, Suppiramaniam V, Konat GW, Reed MN. Neuronal CXCL10/CXCR3 Axis Mediates the Induction of Cerebral Hyperexcitability by Peripheral Viral Challenge. Front Neurosci. 2020 Mar 24;14:220. doi: 10.3389/fnins.2020.00220. PMID: 32265633; PMCID: PMC7105801. 15: Qin C, Liu H, Tang B, Cao M, Yu Z, Liu B, Liu W, Dong Y, Ren H. In Vitro Immunological Effects of CXCR3 Inhibitor AMG487 on Dendritic Cells. Arch Immunol Ther Exp (Warsz). 2020 Apr 1;68(2):11. doi: 10.1007/s00005-020-00577-3. PMID: 32239302. 16: Bakheet SA, Ansari MA, Nadeem A, Attia SM, Alhoshani AR, Gul G, Al-Qahtani QH, Albekairi NA, Ibrahim KE, Ahmad SF. CXCR3 antagonist AMG487 suppresses rheumatoid arthritis pathogenesis and progression by shifting the Th17/Treg cell balance. Cell Signal. 2019 Dec;64:109395. doi: 10.1016/j.cellsig.2019.109395. Epub 2019 Aug 23. PMID: 31449849. 17: Puchert M, Obst J, Koch C, Zieger K, Engele J. CXCL11 promotes tumor progression by the biased use of the chemokine receptors CXCR3 and CXCR7. Cytokine. 2020 Jan;125:154809. doi: 10.1016/j.cyto.2019.154809. Epub 2019 Aug 19. PMID: 31437604. 18: Wang H, Li J, Zhong P, Wang S, Zhang L, Yang R, Wu D, Chen M, Ji A, Li Y, Wang J. Blocking CXCR3 with AMG487 ameliorates the blood-retinal barrier disruption in diabetic mice through anti-oxidative. Life Sci. 2019 Jul 1;228:198-207. doi: 10.1016/j.lfs.2019.04.016. Epub 2019 Apr 27. PMID: 31039363. 19: Ojha A, Bhasym A, Mukherjee S, Annarapu GK, Bhakuni T, Akbar I, Seth T, Vikram NK, Vrati S, Basu A, Bhattacharyya S, Guchhait P. Platelet factor 4 promotes rapid replication and propagation of Dengue and Japanese encephalitis viruses. EBioMedicine. 2019 Jan;39:332-347. doi: 10.1016/j.ebiom.2018.11.049. Epub 2018 Dec 5. PMID: 30527622; PMCID: PMC6354622. 20: Chen Y, Yin D, Fan B, Zhu X, Chen Q, Li Y, Zhu S, Lu R, Xu Z. Chemokine CXCL10/CXCR3 signaling contributes to neuropathic pain in spinal cord and dorsal root ganglia after chronic constriction injury in rats. Neurosci Lett. 2019 Feb 16;694:20-28. doi: 10.1016/j.neulet.2018.11.021. Epub 2018 Nov 15. PMID: 30448292.