NUCC-390, a novel small-molecule CXCR4 receptor agonist, selectively induces CXCR4 receptor internalization while acting antagonistically to AMD3100. This compound facilitates nerve functional recovery following neurodegeneration in vivo.

NUCC-390 (10 μM) produces strong (Ca)i response, but this effect can be blocked by the known potent and selective CXCR4 antagonist AMD3100. NUCC-390 (10 μM; pre-treatment 30 mins) leads to increased levels of pERK, it has the capability of stimulating signaling activity downstream of CXCR4 receptors. NUCC-390 (10 μM; 2 hours) can induce CXCR4 receptor internalization, and non-treated cells exhibit some diffuse expression of CXCR4-YFP throughout the cytosol and clear expression in the cell membrane in HEK cells[1]. NUCC-390 (0-1.25 μM; 24 hours) boosts axonal growth in cultured cerebellar granule neurons (CGNs) via CXCR4[2].

NUCC-390 (hind limb injection; 3.2 mg/kg; twice daily; 3 days) contributes to the functional and anatomical recovery of the neuromuscular junction (NMJ) following an acute nerve terminal damage by α-LTx in CD-1 mice[2].