110078-46-1 Usage
Description
Plerixafor, also known as AMD3100, is a chemokine receptor antagonist specifically designed for CXCR4 and CXCL12-mediated chemotaxis. It is a potent antagonist of the CXCR4 chemokine receptor and is used for stem cell mobilization. Plerixafor is a white solid and is marketed under the brand name Mozobil.
Uses
Used in Hematological Malignancy Treatment:
PLERIXAFOR is used as a hematopoietic stem cell (HSC) mobilizer for patients with non-Hodgkin's lymphoma (NHL) and multiple myeloma (MM). It inhibits the CXCR4 chemokine receptor and blocks the binding of its ligand, stromal cell-derived factor-1-α (SDF-1-α), which helps in mobilizing HSCs to the peripheral blood for collection and subsequent autologous transplantation.
Used in Autologous Hematopoietic Stem Cell Transplantation:
PLERIXAFOR is used as a potent antagonist for the CXCR4 chemokine receptor in autologous hematopoietic stem cell (HSC) transplantation. This process involves the collection of HSCs from the patient, chemoor radiotherapy to eliminate malignant cells, and retransplantation of the stored HSCs. By blocking the activity of the CXCR4 receptor, Plerixafor is capable of mobilizing HSCs into the bloodstream, which is crucial for the transplantation process.
Used in Enhancing Chemotaxis Inhibition:
PLERIXAFOR is used as a chemokine receptor antagonist for CXCR4 and CXCL12-mediated chemotaxis, with IC50 values of 44 nM and 5.7 nM, respectively. This makes it a valuable tool in research and therapeutic applications where the inhibition of chemotaxis is desired.
In vitro
Plerixafor inhibits CXCL12-mediated chemotaxis with a potency lightly better than its affinity for CXCR4. Plerixafor also antagonizes SDF-1/CXCL12 ligand binding with an IC50 of 651 nM. Plerixafor inhibits SDF-1 mediated GTP-binding, SDF-1 mediated calcium flux and SDF-1 stimulated chemotaxis with IC50 of 27 nM, 572 nM and 51 nM, respectively. Plerixafor does not inhibit calcium flux against cells expressing CXCR3, CCR1, CCR2b, CCR4, CCR5 or CCR7 when stimulated with their cognate ligands, nor does Plerixafor inhibit receptor binding of LTB4. Plerixafor does not, on its own, induce a calcium flux in the CCRF–CEM cells, which express multiple GPCRs including CXCR4, CCR4 and CCR7.
In vivo
A single topical application of Plerixafor promotes wound healing in diabetic mice by increasing cytokine production, mobilizing bone marrow EPCs, and enhancing the activity of fibroblasts and monocytes/macrophages, thereby increasing both angiogenesis and vasculogenesis. Cohorts of mice are administered with PBS, IGF1, PDGF, SCF, or VEGF for five consecutive days and Plerixafor on the 5th day. The number and size of the colonies are highest in IGF1 plus Plerixafor injected mice compared to PDGF, SCF and VEGF treated groups, in combination with Plerixafor.
Originator
AnorMED (Canada)
Clinical Use
Chemokine receptor antagonist:
To enhance mobilisation of haematopoietic stem
cells to the peripheral blood for collection and
subsequent autologous transplantation in patients
with lymphoma and multiple myeloma whose cells
mobilise poorly
Side effects
The most common adverse reactions (occurring in more than 10% of patients) observed during plerixafor use include diarrhea, nausea, fatigue, injection-site reactions, headache, arthralgia, dizziness, and vomiting.
Synthesis
Plerixafor can be synthesized by several related procedures starting from tetraazacyclotetradecane, the macrocyclic tetraamine cyclam. The general synthetic strategy entails the masking of three of the four ring nitrogens, followed by alkylation with para-xylylene dibromide, and subsequent removal of the masking groups. In one approach, tetraazacyclotetradecane is protected as the phosphorotriamide derivative by reaction with tris (dimethylamino)phosphine followed by oxidation with carbon tetrachloride and sodium hydroxide. After condensation with xylylene dibromide, the dimeric bis-phosphoramide intermediate is hydrolyzed to plerixafor by treatment with dilute hydrochloric acid solution.
Drug interactions
Potentially hazardous interactions with other drugs
None known
Metabolism
Not metabolised.
About 70% of a dose is eliminated in the urine within 24
hours.
references
[1]zabel ba, wang y, lewén s, berahovich rd, penfold me, zhang p, powers j, summers bc, miao z, zhao b, jalili a, janowska-wieczorek a, jaen jc, schall tj. elucidation of cxcr7-mediated signaling events and inhibition of cxcr4-mediated tumor cell transendothelial migration by cxcr7 ligands. j immunol. 2009 sep 1;183(5):3204-11. [2].li j, oupicky d. effect of biodegradability on cxcr4 antagonism, transfection efficacy and antimetastatic activity of polymeric plerixafor.biomaterials. 2014 jul;35(21):5572-9. [3]. broxmeyer he. chemokines in hematopoiesis. curr opin hematol. 2008 jan;15(1):49-58. [4]. devi s, wang y, chew wk, lima r, a-gonzález n, mattar cn, chong sz, schlitzer a, bakocevic n, chew s, keeble jl, goh cc, li jl, evrard m, malleret b, larbi a, renia l, haniffa m, tan sm, chan jk, balabanian k, nagasawa t, bachelerie f, hidalgo a, ginhoux f, kubes p, ng lg. neutrophil mobilization via plerixafor-mediated cxcr4 inhibition arises from lung demargination and blockade of neutrophil homing to the bone marrow. j exp med. 2013 oct 21;210(11):2321-36.[5]. mcdermott dh, liu q, velez d, lopez l, anaya-o'brien s, ulrick j, kwatemaa n, starling j, fleisher ta, priel da, merideth ma, giuntoli rl, evbuomwan mo, littel p, marquesen mm, hilligoss d, decastro r, grimes gj, hwang st, pittaluga s, calvo kr, stratton p, cowen ew, kuhns db, malech hl, murphy pm. a phase 1
Check Digit Verification of cas no
The CAS Registry Mumber 110078-46-1 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,1,0,0,7 and 8 respectively; the second part has 2 digits, 4 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 110078-46:
(8*1)+(7*1)+(6*0)+(5*0)+(4*7)+(3*8)+(2*4)+(1*6)=81
81 % 10 = 1
So 110078-46-1 is a valid CAS Registry Number.
InChI:InChI=1/C28H54N8.8BrH.2H2O/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;8*1H;2*1H2
110078-46-1Relevant articles and documents
64Cu-AMD3100-A novel imaging agent for targeting chemokine receptor CXCR4
Jacobson, Orit,Weiss, Ido D.,Szajek, Lawrence,Farber, Joshua M.,Kiesewetter, Dale O.
, p. 1486 - 1493 (2009)
CXCR4 is a chemokine receptor which has been shown to be exploited by various tumors for increased survival, invasion, and homing to target organs. We developed a one step radiosynthesis for labeling the CXCR4-specific antagonist AMD3100 with Cu-64 to pro
An Efficient Synthesis of the bis-Tetraazacyclodecane JM3100 Under PTC Conditions
Narayana, P. Venkata,Seelam, Nareshvarma,Prasanna, Bethanamudi
, p. 588 - 591 (2018)
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Preparation method of Plerixafor
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Paragraph 0011; 0046; 0050, (2017/12/29)
The invention discloses a preparation method of Plerixafor, and belongs to the technical field of Plerixafor preparation. Common agents such as ethylenediamine and diethyl malonate are used as starting raw materials; Michael addition and ring formation are performed; then, the materials are bridged with 1,4-bis(halogenated methyl) benzene; then, reduction is performed through an I2-NaBH4 reduction system to obtain the Plerixafor. The cost of the I2-NaBH4 reduction system is low; the operation is safe, simple and convenient; the pure product can be obtained through recrystallization. The preparation method of the Plerixafor provided by the invention has the advantages that the production cost is low; the operation is safe, simple and convenient; byproducts are few; environment protection and economization are realized; the method can be widely applied to medicine development; good application effects can be achieved; good popularization and application values are realized.
IMPROVED AND COMMERCIALLY VIABLE PROCESS FOR THE PREPARATION OF HIGH PURE PLERIXAFOR BASE
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Page/Page column 16; 17, (2014/09/03)
The present invention relates to an improved and commercially viable process for the preparation of ≥ 99.8% pure plerixafor base (1) by HPLC. The process of the present invention involves simple crystallization techniques to isolate the compounds at each step without employing the laborious column chromatography technique. The solid state characteristics of plerixafor base also discussed by PXRD, DSC and I.R spectroscopy.