PlerixaforPlerixafor
MedChemExpress (MCE)
HY-10046
110078-46-1
AMD 3100
JM3100
SID791
99.90%
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Room temperature in continental US
may vary elsewhere.
Plerixafor (AMD 3100) is a selective CXCR4 antagonist with an IC50 of 44 nM. Plerixafor, an immunostimulant and a hematopoietic stem cell (HSC) mobilizer, is an allosteric agonist of CXCR7. Plerixafor inhibits HIV-1 and HIV-2 replication with an EC50 of 1-10 nM.
The CXCR4 inhibitor Plerixafor (AMD3100) is a potent inhibitor of CXCL12-mediated chemotaxis (IC50, 5.7 nM) with a potency slightly better than its affinity for CXCR4. Plerixafor interferes with the interaction of CXCR4 with its natural ligand, SDF-1 (CXCL12). Treating the cells with CCX771 or CXCL11 has no effect on CXCL12-mediated MOLT-4 or U937 TEM. In contrast, 10 μM Plerixafor inhibits CXCL12-mediated TEM in both cells lines[1]. Plerixafor prevents the infiltration of tumor-associated macrophages (TAMs) into the tumor tissues[8].
Plerixafor (2 mg/kg) administration to UUO mice exacerbates renal interstitial T cell infiltration, resulting in increased production of the pro-inflammatory cytokines IL-6 and IFN-γ and decreased expression of the anti-inflammatory cytokine IL-10[5]. Both perivascular and interstitial fibrosis are significantly reduced by the CXCR4 antagonist, Plerixafor (AMD3100) at 8 weeks[6]. LD50, mouse, SC: 16.3 mg/kg
LD50, rat, SC: >50 mg/kg
LD50, mouse and rat, IV injection: 5.2 mg/kg.
Mice[3] Male C57bl/6 mice (6-7 weeks old, weighing 20 g) are used. The animals are acclimated to the housing environment, which is SPF and had a temperature of 22°C and a 12h/12h light/dark cycle for a week. Then, they are randomly divided into following experimental groups, with 8 mice in each group: normal (no specific intervention), UUO+AMD3100 (mice received UUO surgery and 2 mg/kg AMD3100), and UUO+PBS (mice received UUO surgery and the same volume of PBS). AMD3100 and PBS are administered via intraperitoneal injection every day until sacrifice. Rats[4] The CXCR4 antagonist, AMD3100 dissolved in H2O, is delivered in the type 2 diabetic sand rat model at a dose of 6 mg/kg per day for 8 weeks. In complementary studies, the effect of CXCR4 antagonism (AMD3100 6mg/kg/d) on regulatory T cell numbers is examined. For these studies, AMD3100 or vehicle is delivered via minipump for a period of one week.
U87MG cells are seeded in 96-well plates at the density of 6×103 cells in 200 μL/well and treated with CXCL12, Plerixafor or with peptide R. MTT (5 μg/mL) is added at each time point (24, 48, 72 h) during the final 2 h of treatment. After removing cell medium, 100 μL DMSO are added and optical densities measured at 595 nm with a LT-4000MS Microplate Reader. Measurements are made in triplicates from three independent experiments[2].
125I-CXCL12-CXCR4 44 nM (IC50) 125I-CXCL12-CXCR7 HIV-1 1-10 nM (EC50) HIV-2 1-10 nM (EC50)
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[1]. Yang J, et al. Continuous AMD3100 Treatment Worsens Renal Fibrosis through Regulation of Bone Marrow Derived Pro-Angiogenic Cells Homing and T-Cell-Related Inflammation. PLoS One. 2016 Feb 22
11(2):e0149926. [Content Brief]
[2]. Seki JT, et al. Chemical Stability of Plerixafor after Opening of Single-Use Vial. Can J Hosp Pharm. 2017 Jul-Aug
70(4):270-275. [Content Brief]
[3]. Zabel BA, et al. 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. [Content Brief]
[4]. De Clercq E, et al. Mozobil® (Plerixafor, AMD3100), 10 years after its approval by the US Food and Drug Administration. Antivir Chem Chemother. 2019 Jan-Dec
27:2040206619829382. [Content Brief]
[5]. Mercurio L, et al. Targeting CXCR4 by a selective peptide antagonist modulates tumor microenvironment and microglia reactivity in a human glioblastoma model. J Exp Clin Cancer Res. 2016 Mar 25
35:55. [Content Brief]
[6]. Chu PY, et al. CXCR4 Antagonism Attenuates the Development of Diabetic Cardiac Fibrosis. PLoS One. 2015 Jul 27
10(7):e0133616. [Content Brief]
[7]. Schols D, et al. HIV co-receptor inhibitors as novel class of anti-HIV drugs. Antiviral Res. 2006 Sep
71(2-3):216-26. [Content Brief]
[8]. Zheng J, et al. Toward Normalization of the Tumor Microenvironment for Cancer Therapy. Integr Cancer Ther. 2019
18:1534735419862352. [Content Brief]
