AMG487   Click here for help

GtoPdb Ligand ID: 13071

Synonyms: AMG 487 | AMG-487 | compound 47 [PMID: 17448658]
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: AMG487 is a small molecule CXCR3 antagonist [2-3]. It was investigated for activity as a tumour metastasis inhibitor, based on evidence that CXCR3 expressed on tumour cells directly promotes metastasis [4].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 9
Hydrogen bond donors 0
Rotatable bonds 12
Topological polar surface area 96.16
Molecular weight 603.59
XLogP 1.97
No. Lipinski's rules broken 2
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES CCOC1=CC=C(C=C1)N2C(=NC3=NC=CC=C3C2=O)C(C)N(CC4=CC=CN=C4)C(=O)CC5=CC=C(C=C5)OC(F)(F)F
Isomeric SMILES 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
InChI 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
InChI Key WQTKNBPCJKRYPA-UHFFFAOYSA-N
References
1. Bakheet SA, Ansari MA, Nadeem A, Attia SM, Alhoshani AR, Gul G, Al-Qahtani QH, Albekairi NA, Ibrahim KE, Ahmad SF. (2019)
CXCR3 antagonist AMG487 suppresses rheumatoid arthritis pathogenesis and progression by shifting the Th17/Treg cell balance.
Cell Signal, 64: 109395. [PMID:31449849]
2. Jiao H, Pang B, Chiang YC, Chen Q, Pan Q, Ren R, Hu H. (2023)
Structure basis for the modulation of CXC chemokine receptor 3 by antagonist AMG487.
Cell Discov, 9 (1): 119. [PMID:38012179]
3. Johnson M, Li AR, Liu J, Fu Z, Zhu L, Miao S, Wang X, Xu Q, Huang A, Marcus A et al.. (2007)
Discovery and optimization of a series of quinazolinone-derived antagonists of CXCR3.
Bioorg Med Chem Lett, 17 (12): 3339-43. [PMID:17448658]
4. Walser TC, Rifat S, Ma X, Kundu N, Ward C, Goloubeva O, Johnson MG, Medina JC, Collins TL, Fulton AM. (2006)
Antagonism of CXCR3 inhibits lung metastasis in a murine model of metastatic breast cancer.
Cancer Res, 66 (15): 7701-7. [PMID:16885372]