plerixafor

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Ligands
plerixafor

GtoPdb Ligand ID: 844

Synonyms: AMD 3100 | AMD3100 | bicyclam JM-2987 | JM 3100 | Mozobil®

plerixafor is an approved drug (FDA (2008), EMA (2009))

Comment: Plerixafor (AMD3100) is an antagonist of the chemokine (C-X-C motif) receptor 4 (CXCR4) [6]. It acts as a stem cell mobiliser.

View interactive charts of activity data across species

2D Structure

Physico-chemical Properties

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

SMILES / InChI / InChIKey

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

No information available.

No information available.

Summary of Clinical Use
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).

Summary of Clinical Use

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
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.

Mechanism Of Action and Pharmacodynamic Effects

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.