plerixafor   Click here for help

GtoPdb Ligand ID: 844

Synonyms: AMD 3100 | AMD3100 | bicyclam JM-2987 | JM 3100 | Mozobil®
Approved drug PDB Ligand Immunopharmacology Ligand
plerixafor is an approved drug (FDA (2008), EMA (2009))
Compound class: Synthetic organic
Comment: Plerixafor (AMD3100) is an antagonist of the chemokine (C-X-C motif) receptor 4 (CXCR4) [6]. It acts as a stem cell mobiliser.
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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

plerixafor is commercially available from our sponsors

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 Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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 8
Hydrogen bond donors 6
Rotatable bonds 4
Topological polar surface area 78.66
Molecular weight 502.45
XLogP 0.22
No. Lipinski's rules broken 1

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES C1CNCCN(CCCNCCNC1)Cc1ccc(cc1)CN1CCNCCCNCCNCCC1
Isomeric SMILES C1CNCCN(CCCNCCNC1)Cc1ccc(cc1)CN1CCNCCCNCCNCCC1
InChI InChI=1S/C28H54N8/c1-9-29-15-17-31-13-3-21-35(23-19-33-11-1)25-27-5-7-28(8-6-27)26-36-22-4-14-32-18-16-30-10-2-12-34-20-24-36/h5-8,29-34H,1-4,9-26H2
InChI Key YIQPUIGJQJDJOS-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
Plerixafor is an immunostimulant approved for use as a hematopoietic stem cell mobiliser in the treatment of non-Hodgkin lymphoma and multiple myeloma where autologous stem cell transplantation is necessary. The EMA granted plerixafor orphan status in 2011 as an adjunctive treatment to cytotoxic therapy in acute myeloid leukaemia.

Recent studies have suggested the possibility of plerixafor being repurposed for new indications, including recurrent high-grade glioma and pancreatic cancer. Plerixafor is in Phase 1 study (in combination with bevacizumab) for recurrent high-grade glioma (ClinicalTrials.gov identifier NCT01339039).
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Activity appears to arise from antagonism of CXCR4. As a hematopoietic stem cell mobilizer, plerixafor reversibly blocks binding of the ligand stromal cell-derived factor-1-alpha (SDF-1α), to CXCR4 on CD34+ cells, resulting in mobilization of progenitor cells. In the pancreatic cancer scenario, again CXCR4 is inhibited but in this case results in inhbition of mast cell migration to the tumour environment [4] which appears to interrupt the positive feedback loop of mast cell promotion of pancreatic cancer cell transformation and disease progression.

It has been reported by a team from the Cancer Research UK Cambridge Institute that this drug may be beneficial in the treatment of pancreatic cancer as it appears to deplete tumour stromal cells expressing stromal cell-derived factor 1 (SDF-1α, or CXCL12) which act to suppress immune responses. So by inhibiting formation of the desmoplastic microenvironment in which the pancreatic cancer cells develop, plerixafor facilitates improved efficacy of both the immune system and drug therapy in targeting the cancer.
External links Click here for help
For extended ADME data see the following:

Electronic Medicines Compendium (eMC)
Drugs.com
European Medicines Agency (EMA)