UNC 3230

UNC3230 is a potent, selective and ATP-competitive phosphatidylinositol 4-phosphate 5 kinase type 1C (PIP5K1C) inhibitor with an IC50 of ~41 nM. UNC3230 also inhibits PIP4K2C and does not inhibit any of the other lipid kinases. UNC3230 has antinociceptive and anticancer effects[1].

Research Areas >> Cancer

Signaling Pathways >> Others >> Others

Research Areas >> Inflammation/Immunology

IC50: ~41 nM (phosphatidylinositol 4-phosphate 5 kinase type 1C (PIP5K1C))[1]

Membrane PIP2 levels are significantly reduced by ~45% in dorsal root ganglia (DRG) neurons treated with 100 nM UNC3230 (~2-fold above the IC50) relative to vehicle controls. UNC3230 significantly reduces lysophosphatidic acid (LPA)-evoked calcium signaling in cultured DRG neurons relative to vehicle[1].

UNC3230 (2 nmol) significantly increases noxious heat-evoked paw withdrawal latency for two hours after intrathecal injection in wild-type mice, indicating an antinociceptive effect[1]. UNC3230 (2 nmol; intrathecal injection) is administered then one hour later co-injected 1 nmol LPA with UNC3230 (2 nmol, intrathecal injection). UNC3230 significantly blunts thermal hyperalgesia and mechanical allodynia compared to vehicle[1]. UNC3230 (2 nmol; intrathecal injection) significantly blunts thermal hyperalgesia and mechanical allodynia in the complete Freund’s adjuvant (CFA)-inflamed hindpaw (relative to vehicle control) but does not affect thermal or mechanical sensitivity in the control (non-inflamed) hindpaw over a multiday time course[1].

[1]. Wright BD, et al. The lipid kinase PIP5K1C regulates pain signaling and sensitization. Neuron. 2014 May 21;82(4):836-47.

[2]. Peng W, et al. Type Iγ phosphatidylinositol phosphate kinase promotes tumor growth by facilitating Warburg effect in colorectal cancer. EBioMedicine. 2019 Jun;44:375-386.

[3]. Wright BD, et al. Development of a High-Throughput Screening Assay to Identify Inhibitors of the Lipid Kinase PIP5K1C. J Biomol Screen. 2015 Jun;20(5):655-62.