NUCC-390 dihydrochloride is a novel and selective small-molecule CXCR4 receptor agonist[1]. NUCC-390 dihydrochloride induces internalization of CXCR4 receptor[2].
NUCC-390 dihydrochloride (0.625μM-1.25μM; 24h) induces axonal growth in primary cultured neurons via CXCR4 in a dose-dependent manner[1].Treatment of HEK293 cells with NUCC-390 dihydrochloride (10μM; 2h) resulted in a marked internalization of CXCR4-YFP, producing distinct receptor aggregates in the cytoplasm, but excluded from the nucleus. The effects of NUCC-390 dihydrochloride were completely inhibited by AMD-3100 (GC14745)[2].
NUCC-390 dihydrochloride (26mg/kg; ip; 14 days) treatment increased the density of actively regenerating axons in the proximal part of the sciatic nerve in mice with sciatic nerve injury, as well as the number of axons entering the bridging zone[3]. The CXCR4 receptor agonist NUCC-390 dihydrochloride (3.2mg/kg; im; 72h) stimulates the recovery of function of the neuromuscular junction after degeneration of motor axon terminals induced by Taipoxin and promotes nerve regeneration after O. scutellatus scutellatus venom muscle injection in mice[4]. NUCC-390 dihydrochloride (3.2mg/kg; 96h) promotes the recovery of evoked junction potentials (EJPs) of neuromuscular junctions of single muscle fibres of the mouse soleus muscles injected with the venoms of Bungarus caeruleus or β‐bungarotoxin[5].
References:
[1]. Negro S, Zanetti G, Mattarei A, et al. An agonist of the CXCR4 receptor strongly promotes regeneration of degenerated motor axon terminals[J]. Cells, 2019, 8(10): 1183.
[2]. Mishra R K, Shum A K, Platanias L C, et al. Discovery and characterization of novel small-molecule CXCR4 receptor agonists and antagonists[J]. Scientific reports, 2016, 6(1): 30155.
[3]. Zanetti G, Negro S, Megighian A, et al. A CXCR4 receptor agonist strongly stimulates axonal regeneration after damage[J]. Annals of Clinical and Translational Neurology, 2019, 6(12): 2395-2402.
[4]. Stazi M, D’Este G, Mattarei A, et al. An agonist of the CXCR4 receptor accelerates the recovery from the peripheral neuroparalysis induced by Taipan snake envenomation[J]. Plos Neglected Tropical Diseases, 2020, 14(9): e0008547.
[5]. Stazi M, Fabris F, Tan K Y, et al. An agonist of the CXCR4 receptor is therapeutic for the neuroparalysis induced by Bungarus snakes envenoming[J]. Clinical and Translational Medicine, 2022, 12(1)
NUCC-390 dihydrochloride是一种新型选择性小分子CXCR4受体激动剂[1]。NUCC-390 dihydrochloride可诱导CXCR4受体内化[2]。
NUCC-390 dihydrochloride（0.625μM-1.25μM；24h）以剂量依赖性方式通过CXCR4诱导原代培养神经元的轴突生长[1]。用NUCC-390 dihydrochloride（10μM；2h）处理HEK293细胞可导致CXCR4-YFP明显内化，在细胞质中产生明显的受体聚集体，但被排除在细胞核之外。NUCC-390 dihydrochloride的作用被AMD-3100（GC14745）完全抑制[2]。
NUCC-390 dihydrochloride（26mg/kg；ip；14 days）治疗增加了坐骨神经损伤小鼠坐骨神经近端主动再生轴突的密度，以及进入桥接区的轴突数量[3]。CXCR4受体激动剂NUCC-390 dihydrochloride（3.2mg/kg；im；72h）改善了Taipoxin引起的运动轴突终末变性后神经肌肉接头功能的恢复，并促进了小鼠肌肉注射O. scutellatus scutellatus毒液后的神经再生[4]。NUCC-390 dihydrochloride（3.2mg/kg；96h）促进注射了银环蛇毒液或β‐银环蛇毒素的小鼠比目鱼肌单个肌纤维神经肌肉接头的诱发接头电位 (EJP) 的恢复[5]。