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Phosphatidylinositol-4-phosphate 5-kinase type-1 γ (PIP5K1C) is a lipid kinase that generates phosphatidylinositol-4,5-bisphosphate (PIP₂) in nociceptive dorsal root ganglia (DRG). Pain sensitization is regulated by multiple signaling pathways that are initiated by phospholipase C-mediated hydrolysis of PIP₂. UNC3230 is a small molecule inhibitor of PIP5K1C (IC₅₀ = 41 nM, K_d = 51 nM). It does not inhibit any other lipid kinases that regulate phosphoinositide levels, including phosphatidylinositol 3-kinases. At 100 nM, UNC3230 decreases PIP₂ membrane levels in cultured DRG neurons by 45% and significantly reduces calcium signaling. At 2 nM, it displays antinociceptive effects in mouse models of chronic pain when administered intrathecally or injected into inflamed hindpaw.

UNC 3230 is a potent inhibitor of PIP5K1C.

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[1] BRITTANY D WRIGHT. The lipid kinase PIP5K1C regulates pain signaling and sensitization.[J]. Neuron, 2014: 836-847. DOI: 10.1016/j.neuron.2014.04.006