IDO5L

IDO5L is a potent indoleamine 2,3-dioxygenase (IDO) inhibitor with an IC₅₀ of 67 nM. IC50 & Target: IC50: 67 nM (IDO), 19 nM (IDO, in HeLa cell)^[1] In Vitro: IDO5L (Compound 5l) is a potent (HeLa IC₅₀=19 nM) inhibitor of IDO^[1]. IDO5L is one of the highest potent inhibitors of the IDO1 (IC₅₀=19 nM, in HeLa cell assay)^[2]. In Vivo: Testing of IDO5L in mice demonstrates pharmacodynamic inhibition of IDO, as measured by decreased kynurenine levels (>50%) in plasma and dose dependent efficacy in mice bearing GM-CSF-secreting B16 melanoma tumors. Initial oral pharmacokinetic studies show that IDO5L is rapidly cleared (t_1/2<0.5 h) and that oral administration will not be a suitable dosing method for in vivo studies. The measured plasma exposure (2.5 μM) of IDO5L during this period exceeded our calculated mouse protein binding adjusted B16 cellular IC₅₀ (PB_adjIC₅₀=1.0 μM, murine cellular B16 IC₅₀=46 nM). Notably, kynurenine levels increase back to baseline after 4 h as IDO5L exposure levels decreased below the mouse PB_adjIC₅₀ from 1.0 to 0.1 μM^[1].