| Identification | Back Directory | [Name]
Plerixafor 8HCl (AMD3100 8HCl) | [CAS]
155148-31-5 | [Synonyms]
SID791
JM3100
CS-907
AMD3100
Bicyclam
BISCYCLAM
AMD3100 HCl
JM 3100 8HCl
AMD3100 8HCl
Plerixafor hcl
Plerixafor 8HCl
Plerixafor-d8 8HCl
AMD 3100 octahydroch
Plerixafor HCL(JM 3100)
Plerixafor hydrochloride
JM3100 octahydrochloride
SID791 octahydrochloride
Plerixafor 8HCl (DB06809)
AMD3100 OCTAHYDROCHLORIDE
Plerixafor 8HCl (AMD3100)
CXCR4 Antagonist I, AMD3100
Plerixafor hydrochloride salt
Plerixafor Hydrochloride (1:8)
Plerixafor (octahydrochloride)
Plerixafor 8HCl (AMD3100 8HCl)
AMD 3100 octahydrochloride(8HCl)
AMD 3100 octahydrochloride, >=98%
amd3100 octahydrochloride hydrate
Plerixafor (hydrochloride hydrate)
AMD3100 hydrate octahydrochloride
InSolution? CXCR4 Antagonist I, AMD3100
Plerixafor 8HCl (AMD3100 8HCl) USP/EP/BP
AMD3100 OCTAHYDROCHLORIDE HYDRATE ANHYDROUS
AMD3100 OCTAHYDROCHLORIDE;AMD-3100; AMD 3100
Plerixafor(SynonyM: AMD3100 octahydrochloride hydrate)
CXCR4 Antagonist I, AMD3100 - CAS 155148-31-5 - Calbiochem
InSolution CXCR4 Antagonist I, AMD3100 - CAS 155148-31-5 - Calbiochem
1,1'-[1,4-Phenylenebis(methylene)]bis[1,4,8,11-tetraazacyclotetradecane]
1,4-Bis[(1,4,8,11-tetraazacyclotetradecan-1-yl)methyl]benzene Octahydrochloride
1,1'-[1,4-PHENYLENEBIS(METHYLENE)]BIS-1,4,8,11-TETRAAZACYCLOTETRADECANE OCTAHYDROCHLORIDE
1,1'-[1,4-Phenylenebis(methylene)]bis[1,4,8,11-tetraazacyclotetradecane] hydrochloride (1:8)
1,4,8,11-Tetraazacyclotetradecane, 1,1'-(1,4-phenylenebis(methylene))bis-, octahydrochloride
1,4,8,11-Tetraazacyclotetradecane, 1,1'-[1,4-phenylenebis(methylene)]bis-, hydrochloride (1:8)
1,1'-[1,4-Phenylenebis-(methylene)]-bis-(1,4,8,11-tetraazacyclotetradecane) octahydrochloride hydrate
JM3100, SID791, 1,1μ-[1,4-Phenylenebis(methylene)]bis-1,4,8,11-tetraazacyclotetradecane octahydrochloride
1,1'-[1,4-Phenylenebis-(methylene)]-bis-(1,4,8,11-tetraazacyclotetradecane) octahydrochloride, min. 95 % (NMR) | [EINECS(EC#)]
828-184-5 | [Molecular Formula]
C28H54N8 | [MDL Number]
MFCD04974488 | [MOL File]
155148-31-5.mol | [Molecular Weight]
502.78 |
| Chemical Properties | Back Directory | [Melting point ]
188 - 193°C (dec.) | [storage temp. ]
−20°C
| [solubility ]
H2O: ≥10 mg/mL, clear
| [form ]
solid
| [color ]
White | [Water Solubility ]
Soluble in water (100mM) | [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. |
| Hazard Information | Back Directory | [Description]
Plerixafor (155148-31-5) is a highly selective CXCR4 antagonist (IC50 = 20-130 nM).1,2 Originally investigated as an HIV replication inhibitor.3 Plerixafor has been investigated for the treatment autoimmune diseases and various cancers.4 Clinically useful for the mobilization of hematopoietic stem cells in the treatment of blood cancers. | [Uses]
A specific CXCR4 antagonist. | [Uses]
Plerixafor 8HCl (AMD3100 8HCl) is the hydrochloride of Plerixafor, a chemokine receptor antagonist for CXCR4 and CXCL12-mediated chemotaxis with IC50 of 44 nM and 5.7 nM, respectively - See more at: http://www.selleckchem.com/products/plerixafor-8hcl-db06 | [General Description]
A symmetrical bicyclam compound that antagonizes CXCL12 (SDF1) binding to CXCR4 (IC50 = 108 and 245 nM using rat and human CXCR4, respectively) and inhibits SDF1-induced Ca2+ flux (by 100% at 100 ng/ml in SUP-T1 and THP-1 cultures) as well as CXCR4-, but not CCR5-, mediated HIV infection (IC50 ≤200 nM), while enhancing the binding of SDF1 to CXCR7 (by ~60% at 1 mM with CXCR7-expressing HEK293T cells) and SDF1-induced β-arrestin recruitment to CXCR7 (EC50 = 6.48 and 11.8 nM, in the presence and absence of 10 μM AMD3100, respectively). Administration AMD3100 via intravenous infusion is also reported to result in hematopoietic stem cell mobilization in humans, dogs, and mice in vivo. Exhibits 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¨C68% yield.
| [Enzyme inhibitor]
This metal ion-chelating immunostimulant (FW = 502.80 g/mol; CAS
155148-31-5), also known by its code names AMD3100 and JM3100, its
trade name Mozobil? as well as its systematic name 1,1’-[1,4-
phenylenebis (methylene) ]bis-[1,4,8,11-tetraazacyclotetradecane], is an a-C-
X-C chemokine receptor CXCR4 antagonist (or partial agonist) and an
allosteric CXCR7 agonist (1-4). The active chemical form is likely to
contain divalent zinc ion. (See also TC 14012) Likely Mode of Action: The
CXCR4 a-chemokine is stimulated by Stromal cell-Derived Factor-1 (or
SDF-1) that plays roles in hematopoietic stem cell homing to the bone
marrow and in hematopoietic stem cell (HSC) quiescence. CXCR7) is a G-
protein-coupled receptor (GPCR) that binds the chemokines CXCL12/SDF-
1 and CXCL11 and serves as a coreceptor for human immunodeficiency
viruses. Plerixafor inhibits the replication of various HIV-1 and HIV-2
strains in various cell lines (EC50 = 1-10 ng/mL, or >100,000x lower than its
cytotoxic concentration of 500 μg/mL). When combined with either 3'-
azido-2',3' -dideoxythymidine or 2',3'-dideoxyinosine, JM3100 achieved a
additive inhibition of HIV replication, and when repeatedly subcultivated in
the presence of JM3100, with the virus remaining sensitive to the
compound for at least 30 passages in culture. AMD3100 blocks HIV-1
entry and membrane fusion via the CXCR4 co-receptor, blocking the
latter’s role as both a HIV-1 co-receptor and a CXC-chemokine receptor
. Use as an Investigational Drug: Plerixafor’s discovery provided a new
way to mobilize HSC for autologous transplantation. In 2008, plerixafor
was approved by the FDA for the mobilization of hematopoietic stem cells.
Plerixafor is also an investigational drug for the treatment of WHIM
Syndrome (standing for Warts, Hypogammaglobulinemia, Infection &
Myelokathexis Syndrome), a rare congenital immunodeficiency disorder
characterized by chronic noncyclic neutropenia and arising from gain-of-
function deletion mutations in CXCR4. In a Phase-I study, circulating
leukocytes were durably increased throughout the trial in all patients, and
this was associated with fewer infections and improvement in warts in
combination with imiquimod; however immunoglobulin levels and specific
vaccine responses were not fully restored. Metal Ion Binding: Plerixafor
binds zinc, copper nickel, cobalt and2 +rhodium ions, and the biologically
active form is the 1:2 Plerixafor-Zn ternary complex (FW = 627.53
g/mol). Other CXCR4 antagonists include: AMD070, T140, FC131, FC122,
with several being evident metal ion-binding chelators. The diversity of
their structures suggests the possibility that they may act as divalent
metallophores, a unique class of organic molecules that facilitate metal ion
transfer across membrane bilayers in a manner akin to the valinomycin-
facilitated transport of potassium ion or by means of a vesicle pathway,
such as receptor-mediated endocytosis. | [storage]
-20°C (desiccate) | [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 |
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