CRT0273750

Potency assay, off target (cells): IOA-289 was tested in fibrosis screening panels of human primary cells in vitro. Tested at 6 uM, IOA-289 significantly decreased the activity of the inflammation-related markers soluble interleukin 8 and 6 (sIL-8, sIL-6) and monocyte chemoattractant protein 1 (MCP-1), the myofibroblast activation-related marker α-smooth muscle actin (αSMA), the fibrosis-related matrix marker collagen III (Col-III) and the tissue remodeling/wound healing markers epidermal growth factor receptor (EGFR) and soluble vascular endothelial growth factor (sVEGF). DOI: 10.1016/j.iotech.2023.100384

Potency assay (off target): In vitro safety pharmacology studies showed that IOA-289 has no to minimal potential off-target interactions: on a panel of lipid receptors (LPA1, LPA2, LPA3, LPA5, S1P1, S1P2, SP3, S1P4 and S1P5) and on the SafetyScreen44™ panel, IOA-289 only showed sub-micromolar binding to the 5-hydroxytryptamine 2B (5-HT2B) receptor and was confirmed to be an antagonist of 5-HT2B with an IC50 value of 2.5 μM. (DOI: 10.1016/j.iotech.2023.100384)

Potency assay (off target): In the GLP hERG assay, IOA-289 inhibited the hERG tail current with an IC50 of 1.03 μM. Based on the high potency of IOA-289 in human plasma and the relatively high plasma protein binding in human of 99%, these activities are not considered to be a significant safety concern and do not impede further development. (DOI: 10.1016/j.iotech.2023.100384)