PLERIXAFOR

Bezeichnung:PLERIXAFOR

CAS-Nr110078-46-1

Englisch Name:PLERIXAFOR

CBNumberCB11011749

SummenformelC28H54N8

Molgewicht502.78

MOL-Datei110078-46-1.mol

PLERIXAFOR physikalisch-chemischer Eigenschaften

Schmelzpunkt	122-125°C
Siedepunkt	657.5±55.0 °C(Predicted)
Dichte	0.962
storage temp.	Keep in dark place,Inert atmosphere,2-8°C
Löslichkeit	Methanol (Slightly), Water (Slightly)
Aggregatzustand	Solid
pka	10.60±0.20(Predicted)
Farbe	White to Pale Beige
Stabilität	Hygroscopic
CAS Datenbank	110078-46-1

Sicherheit

HS Code

29339900

Gefahreninformationscode (GHS)

PLERIXAFOR Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
Autologous hematopoietic stem cell (HSC) transplantation, a standard treatment for hematological malignancies, such as non-Hodgkin’s lymphoma or multiple myeloma, involves collection of HSCs from the patient, chemo- or radiotherapy of the patient to eliminate malignant cells, and retransplantation of the stored HSCs.
Plerixafor is a potent antagonist of the CXCR4 chemokine receptor and a first-in-class drug for stem cell mobilization. CXCR4 is specific for stromal-derived-factor-1 (SDF-1), a molecule endowed with potent chemotactic activity forlymphocytes. Because the interaction between SDF-1 and CXCR4 plays an important role in holding HSCs in the bone marrow, drugs that block the activity of CXCR4 receptor are capable of mobilizing HSCs into the bloodstream. In vitro, plerixafor potently blocks SDF-1 binding of CXCR4 and inhibits SDF-1-induced calcium flux (IC₅₀ = 0.01-0.13 mg/mL) and chemotaxis (IC₅₀ = 0.13 mg/mL) in several different cell types. Plerixafor, in combination with G-CSF, is specifically indicated to mobilize HSCs to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin’s lymphoma and multiple myeloma.
Chemische Eigenschaften
White Solid
Originator
AnorMED (Canada)
Verwenden
Plerixafor is a hematopoietic stem cell (HSC) mobilizer that inhibits the CXCR4 chemokine receptor and blocks binding of its ligand, stromal cell-derived factor-1-α (SDF-1-α). This agent was approved on Dec. 15, 2008, as treatment in combination with granulocyte-colony stimulating factor (G-CSF) to mobilize HSCs to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin''s lymphoma (NHL) and multiple myeloma (MM). Selective CXCR4 antagonist.
Verwenden
Plerixafor is a chemokine receptor antagonist for CXCR4 and CXCL12-mediated chemotaxis with IC50 of 44 nM and 5.7 nM, respectively
Definition
ChEBI: Plerixafor is an azamacrocycle consisting of two cyclam rings connected by a 1,4-phenylenebis(methylene) linker. It is a CXCR4 chemokine receptor antagonist and a hematopoietic stem cell mobilizer. It is used in combination with grulocyte-colony stimulating factor (G-CSF) to mobilize hematopoietic stem cells to the perpheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma and multiple myeloma. It has a role as an immunological adjuvant, an antineoplastic agent, an anti-HIV agent and a C-X-C chemokine receptor type 4 antagonist. It is an azamacrocycle, a crown amine, a secondary amino compound, an azacycloalkane, a tertiary amino compound and a member of benzenes. It is functionally related to a 1,4,8,11-tetraazacyclotetradecane.
Trademarks
Mozobil
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
Nebenwirkungen
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.
Synthese
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.
Stoffwechsel
Not metabolised.
About 70% of a dose is eliminated in the urine within 24 hours.
Einzelnachweise
[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

PLERIXAFOR Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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