Through binding with CC- and CXC-chemokines, CCR and CXCR, the subsets of the chemokine receptor family can trigger an intracellular signal transduction cascade, thus mediating the recruitment of immune cells to the inflammation or infection sites and implicated in several immuno-related disease states, organogenesis, angiogenesis and tumor growth and metastasis. Plerixafor Octahydrochloride is the hydrochloride form of AMD3100. AMD3100 is a selective antagonist of CXCR4 with IC50 values ranging in 0.01-0.13μg/ml for antagonizing SDF-1, but not itself, activated calcium flux in different cells tested, including CXCR4-transfected U87 and CD4 cells, freshly isolated PBMCs, SupT1, THP-1, HSB-2, Molt-4 and L1210 cells. The inhibitory effect of AMD3100 against the induced endocytosis of CXCR4 is selectively SDF-1-dependent but not phorbol ester. Pre-incubated with AMD3100 at concentration of 0.04, 0.2, 1, 5 and 25μg/ml could dose-dependently inhibit the SDF-1-induced (200 ng/ml) chemotaxis of human PBMCs[1]. In vivo study showed that intraperitoneal injection with 5mg/kg AMD3100 can alter the potential of mesenchymal stem cells mobilization induced by different growth factors, including IGF-1, SCF, PDGF and VEGF, in mice, which may be mediated through Akt/PI3K, MEK1/2-Erk1/2 and smad2/3 as key signaling pathways[2].
作用机制
Not found
Plerixafor octahydrochloride/盐酸普乐沙福 细胞实验
Cell Line
Concentration
Treated Time
Description
References
KU812F cells
50 μM
3 h
Plerixafor inhibited the chemotactic response of CML cells to SDF1
Leukemia. 2012 May;26(5):985-90.
KU812F cells
50 μM
3 h
Plerixafor inhibited the trans-endothelial migration of CML cells
Leukemia. 2012 May;26(5):985-90.
EJ cells
50 μM
24 h
To evaluate the effect of Plerixafor on the CXCR4 downstream signaling pathway, results showed that Plerixafor significantly inhibited the phosphorylation of Erk and Akt
Sci Adv. 2023 Mar;9(9):eabq8225.
KU812F cells
50 μM
3 h
Plerixafor reduced the adhesion of CML cells to bone marrow microenvironment components
Leukemia. 2012 May;26(5):985-90.
KU812F cells
50 μM
3 h
Plerixafor reversed the protective effect of bone marrow stromal cells and re-sensitized CML cells to nilotinib
Leukemia. 2012 May;26(5):985-90.
MDA-MB-231 cells
10 μg/mL
1 h
To study the uptake of Plerixafor-modified nanocarriers in CXCR4-expressing cells, results showed that Plerixafor-modified carriers were uptaken at a higher rate in CXCR4-expressing cells compared to unmodified carriers.
Biomacromolecules. 2015 Aug 10;16(8):2412-7.
Plerixafor octahydrochloride/盐酸普乐沙福 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Whole body irradiation (WBI) and skin irradiation (SI) model
Subcutaneous injection
5 mg/kg
Single injection, administered on day 6
To evaluate the effect of Plerixafor in combination with G-CSF on MSC-FMB in correcting radiation-induced wound healing deficits, results showed that Plerixafor enhanced the efficacy of MSC-FMB.
J Invest Dermatol. 2013 Feb;133(2):553-61
Mice
Spinal cord injury model
Subcutaneous injection
5 mg/kg
Once daily for 3 days
Plerixafor effectively liberates HSPCs and mature leukocytes from the bone marrow of SCI mice, partly reversing bone marrow failure.
Nat Commun. 2020 Jul 24;11(1):3702
BALB/c nude mice
EJ xenograft model
Intravenous injection
500 μM, 100 μl
Once every 2 days for a total of five times
To evaluate the effect of Plerixafor on tumor growth, results showed that Plerixafor significantly inhibited tumor growth
Sci Adv. 2023 Mar;9(9):eabq8225.
Rhesus macaques
Gene therapy model
Intravenous injection
1 mg/kg
Single dose, on day 5
Used to mobilize CD34+ cells for gene therapy
Nat Commun. 2023 Oct 12;14(1):6291
Mice
BCR-ABL-positive leukemia mouse model
Subcutaneous injection
5 mg/kg
Once daily for 10 days
Plerixafor in combination with nilotinib significantly prolonged survival and reduced leukemia burden in mice
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