Plerixafor (octahydrochloride)

Plerixafor octahydrochloride (AMD3100 octahydrochloride) is a selective CXCR4 antagonist with an IC₅₀ of 44 nM. IC50 & Target:IC50: 44 nM (CXCR4)^[1] In Vitro: 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. 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 (10 μM)-treated cells show a moderate reduction in cell proliferation compared to CXCL12-stimulated cells, which do not reach statistical significance^[2]. In Vivo: 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^[3]. Both perivascular and interstitial fibrosis are significantly reduced by the CXCR4 antagonist, Plerixafor (AMD3100) at 8 weeks^[4]. LD50, mouse, SC: 16.3 mg/kg; LD50, rat, SC: >50 mg/kg; LD50, mouse and rat, IV injection: 5.2 mg/kg.