Plerixafor (AMD3100)

Plerixafor(AMD3100)是CXCR4以及CXCL12介导的趋化性的小分子抑制剂，IC50值分别为44 nM和5.7 nM [1]。

CXCR4和SDF-1是调节肿瘤细胞浸润和转移过程中的关键因素，Plerixafor可以防止SDF-1结合CXCR4从而抑制癌症转移[2]。Plerixafor干扰CXCL12/CXCR4介导的骨髓造血干细胞在骨髓中的保留，导致它们在血液中的运动[3]。Plerixafor扩大肺中循环性中性粒细胞的释放，同时防止中性粒细胞回到骨髓[4]。三个WHIM综合症的成年人连续6个月每天两次皮下注射0.01至0.02毫克/千克的Plerixafor，他们的循环白细胞不断增加，相关的感染更少[5]。

参考文献：
[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 clinical trial of long-term, low-dose treatment of WHIM syndrome with the CXCR4 antagonist plerixafor. Blood. 2014 Apr 10;123(15):2308-16.