Fricker Simon P
Genzyme Corp., Framingham, MA 01701-9322, USA.
Expert Opin Investig Drugs. 2008 Nov;17(11):1749-60. doi: 10.1517/13543784.17.11.1749.
Hematopoietic stem cell (HSC) transplantation is a treatment option for hematological malignancies. Current mobilization regimes frequently result in inadequate numbers of HSC for transplant therefore alternative methods of mobilization are required.
The chemokine receptor CXCR4 and ligand SDF-1 are integrally involved in HSC homing and mobilization. Disruption of the SDF-1/CXCR4 axis by the CXCR4 anatagonist, plerixafor, is shown to improve HSC mobilization.
The molecular and in vivo pharmacology of plerixafor and subsequent clinical development is reviewed.
RESULTS/CONCLUSION: Preclinical studies demonstrate that plerixafor is a selective antagonist of CXCR4 and can rapidly mobilize HSC. Clinical trials demonstrated improved HSC mobilization when plerixafor was included in the mobilization regimen. These data suggest the potential for a significant role for plerixafor in hematological disease.
造血干细胞（HSC）移植是血液系统恶性肿瘤的一种治疗选择。目前的动员方案常常导致用于移植的HSC数量不足，因此需要其他动员方法。
趋化因子受体CXCR4及其配体SDF-1与HSC归巢和动员密切相关。CXCR4拮抗剂普乐沙福破坏SDF-1/CXCR4轴可改善HSC动员。
对普乐沙福的分子和体内药理学及其后续临床开发进行综述。
结果/结论：临床前研究表明，普乐沙福是CXCR4的选择性拮抗剂，可快速动员HSC。临床试验表明，当普乐沙福纳入动员方案时，HSC动员得到改善。这些数据表明普乐沙福在血液疾病中可能发挥重要作用。
