155148-31-5

Basic information

• Product Name: Plerixafor 8HCl (AMD3100 8HCl)
• Synonyms: 1,1'-[1,4-PHENYLENEBIS(METHYLENE)]BIS-1,4,8,11-TETRAAZACYCLOTETRADECANE OCTAHYDROCHLORIDE;AMD3100;AMD3100 OCTAHYDROCHLORIDE;BISCYCLAM;JM3100;SID791;AMD3100 OCTAHYDROCHLORIDE HYDRATE ANHYDROUS;amd3100 octahydrochloride hydrate
• CAS NO: 155148-31-5
• Molecular Formula: C28H54N8
• Molecular Weight: 502.78
• EINECS: 1592732-453-0
• Product Categories: Inhibitors
• Mol File: 155148-31-5.mol
• Article Data: 0

Chemical Properties

• Boiling Point: 657.5 °C at 760 mmHg
• Flash Point: 361.8 °C
• Appearance: /solid
• Density: 0.962g/cm3
• Storage Temp.: −20°C
• Solubility: H2O: ≥10 mg/mL, clear
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in distilled water may be stored at -20°C for up to 2 months.
• CAS DataBase Reference: Plerixafor 8HCl (AMD3100 8HCl)(CAS DataBase Reference)
• NIST Chemistry Reference: Plerixafor 8HCl (AMD3100 8HCl)(155148-31-5)
• EPA Substance Registry System: Plerixafor 8HCl (AMD3100 8HCl)(155148-31-5)

Safety Data

• Safety Statements: 22-24/25
• WGK Germany: 3
• Hazardous Substances Data: 155148-31-5(Hazardous Substances Data)

Usage

Description

Plerixafor 8HCl (AMD3100 8HCl) is a symmetrical bicyclam compound that acts as a highly selective CXCR4 antagonist with an IC50 of 20-130 nM. It was originally investigated as an HIV replication inhibitor and has since been explored for the treatment of autoimmune diseases and various cancers. Plerixafor 8HCl is clinically useful for the mobilization of hematopoietic stem cells in the treatment of blood cancers.

Uses

Used in Hematopoietic Stem Cell Mobilization:
Plerixafor 8HCl (AMD3100 8HCl) is used as an immunostimulant for the mobilization of hematopoietic stem cells in cancer patients. It functions as a hematopoietic stem cell (HSC) mobilizer that inhibits the CXCR4 chemokine receptor and blocks the binding of its ligand, stromal cell-derived factor-1-α (SDF-1-α).
Used in Cancer Treatment:
Plerixafor 8HCl (AMD3100 8HCl) is used as a chemokine receptor antagonist for CXCR4 and CXCL12-mediated chemotaxis with IC50 values of 44 nM and 5.7 nM, respectively. It has been investigated for the treatment of various cancers, including autoimmune diseases.
Used in HIV Infection:
Plerixafor 8HCl (AMD3100 8HCl) is used as an antagonist that inhibits CXCR4-, but not CCR5-, mediated HIV infection with an IC50 of less than or equal to 200 nM.
Used in Pharmaceutical Research:
Plerixafor 8HCl (AMD3100 8HCl) is used as a specific CXCR4 antagonist in pharmaceutical research, exhibiting no inhibitory effects against chemokine-induced signaling via CXCR1/2/3 or CCR1/2/3/4/5/6/7/8/9.

Biological Activity

Highly selective CXCR4 chemokine receptor antagonist (IC 50 values are 0.02 - 0.13 and > 25 μ M for CXCR4 and all other chemokine receptors respectively). Switches inflammatory responses from Th2 to Th1 type and reduces airway hyperresponsiveness in a mouse model of asthma. Potently inhibits HIV-1 and HIV-2 replication in vitro (EC 50 = 4 - 35 nM) and mobilizes hematopoietic stem cells in vivo .

Biochem/physiol Actions

Cell permeable: yes

Clinical Use

Plerixafor hydrochloride, a chemokine CXCR4 (SDF-1) antagonist, was launched by Genzyme for the treatment of enhancing mobilization of hematopoietic stem cells for autologous transplantation in patients with lymphoma and enhancing mobilization of hematopoietic stem cells for transplantation in patients with multiple myeloma. Being a CXCR4 antagonist, a specific cellular chemokine receptor, plerixafor triggers the rapid movement of stem cells out of the bone marrow and into circulating blood where the stem cells can be collected for use in stem cell transplants. Regarding its use for cardiac applications, some clinical data suggests that the presence of stem cells circulating in the bloodstream or directly injected into the hearts of patients who have suffered a heart attack may result in improved cardiac function.

Synthesis

A concise one-pot synthesis was achieved by a rather novel nitrogen protecting strategy. Tetraazacyclotetradecane 88 was protected as its phosphorotriamide 89 by reaction with POCl3 and Et3N in hot DMF. Without isolation, compound 89 was bis-alkylated with dibromide 90 in the presence of sodium carbonate in refluxing DMF overnight to give bis-phosphoramide 91. The crude dimeric bis-phosphoramide was hydrolyzed with 3 M HCl to afford plerixafor hydrochloride (XV) in 62–68% yield.

References

1) Donzella, et al. (1998), AMD3100, A Small Molecule Inhibitor of HIV-1 Entry via the CXCR4 Co-Receptor; Nat. Med. 4 72 2) Hatse et al. (2002), Chemokine Receptor Inhibition by AMD3100 Is Strictly Confined to CXCR4; FEBS Lett. 527 255 3) Bridger et al. (1995), Synthesis and Structure-Activity Relationships of Phenylenebis(methylene)-linked Bis-Tetraazamacrocycles That Inhibit HIV Replication. Effects of Macrocyclic Ring Size and Substituents on the aromatic Linker; J. Med. Chem. 38 366 4) Wang et al. (2020), CXCR4 antagonist AMD3100 (plerixafor): from an impurity to a therapeutic agent; Pharmacol. Res. 159 105010