ALX40-4C是一种趋化因子受体(CXCR4)抑制剂，能够抑制SDF-1与CXCR4结合，Ki值为1μM，具有抗HIV-1作用；ALX40-4CTrifluoroacetate同时为APJ受体拮抗剂，IC50值为2.9μM。
ALX 40-4C is a small peptide inhibitor of the chemokine receptor CXCR4, inhibits SDF-1 from binding CXCR4 with a Ki of 1 μM, and suppresses the replication of X4 strains of HIV-1; ALX 40-4C Trifluoroacetate also acts as an antagonist of the APJ receptor, with an IC50 of 2.9 μM.
ALX 40-4C is a small peptide inhibitor of the chemokine receptor CXCR4, interacts with the second extracellular loop of CXCR4 and inhibits infection exclusively by blocking direct virus-CXCR4 interactions[1]. ALX 40-4C shows potent anti HIV-1 effect, with EC50s of 0.34 ± 0.04 μg/mL, 0.37 ± 0.01 μg/mL for HIV-1 NL4-3, NC10, and 0.18 ± 0.11 μg/mL, 0.06 ± 0.02 μg/mL for HIV-1 HXB2, HC43, respectively, and with a CC50 (50% cytotoxic concentration) of 21 μg/mL. ALX 40-4C also exhibits potent activity against env-recombinant HIV, with EC50s of 0.38 ± 0.01 μg/mL, 0.40 ± 0.0 μg/mL for HIV-1 NL4-3 env, NC10, and 1.34 ± 0.06 μg/mL, 1.02 ± 0.29 μg/mL for HIV-1 HXB2 env, HC43, and a CC50 of 21 μg/mL[2]. ALX 40-4C binds to APJ with an IC50 of 2.9 μM. ALX 40-4C inhibits HIV-1 gp120/APJ-mediated cell membrane fusion, with an IC50s of 3.41 μM and 3.1 μM for IIIB isolate and 89.6 isolate, respectively[3].
[1]. Doranz BJ, et al. Safe use of the CXCR4 inhibitor ALX40-4C in humans. AIDS Res Hum Retroviruses. 2001 Apr 10;17(6):475-86. [2]. Armand-Ugón M, et al. HIV-1 resistance to the gp41-dependent fusion inhibitor C-34. Antiviral Res. 2003 Jul;59(2):137-42. [3]. Zhou N, et al. Binding of ALX40-4C to APJ, a CNS-based receptor, inhibits its utilization as a co-receptor by HIV-1. Virology. 2003 Jul 20;312(1):196-203.
Kinase experiment: | The stably transfected cells are harvested in PBS (Ca2+ and Mg2+ free) plus 0.5 nM EDTA and washed twice with PBS. Ligand binding experiments are performed using a single concentration (0.2 nM) of 125I-Apelin-13 in the absence or presence of increasing concentrations of unlabeled Apelin-13 or ALX 40-4C in a final volume of 100 μL of binding buffer (50 nM Hepes, pH 7.4, 1 nM CaCl2, 5 nM MgCl2, 0.1% bovine serum albumin) containing 5 × 105 cells. Nonspecific binding is determined by the addition of 1 μM unlabeled Apelin-13. Samples are incubated for 90 min at room temperature. The incubation is terminated by separating the cells from the binding buffer by centrifugation and washing once with 500 μL of cold binding buffer. Bound ligands are determined by counting gamma emissions. At least three independent experiments are performed[3]. |
参考文献: [1]. Doranz BJ, et al. Safe use of the CXCR4 inhibitor ALX40-4C in humans. AIDS Res Hum Retroviruses. 2001 Apr 10;17(6):475-86. | |
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