IC50: 59 nM
IDO-IN-1 is an indoleamine-2,3-dioxygenase (IDO) inhibitor.
IDO is expressed in various tissues throughout the body but mainly in cells within the immune system where it is induced in dendritic cells and macrophages at sites of inflammation by cytokines. The overexpression of IDO has been implicated in a variety of diseases, such as cancer, neurodegenerative disorders, age-related cataract, and HIV encephalitis.
In vitro: In previous study, IDO-IN-1 was found to have improved in-vitro human intrinsic clearances without loss in IDO cellular potency [1].
In vivo: IDO-IN-1 analog, named 5l, was chosen for further in vivo studies because of its improved physical chemical properties compared to IDO-IN-1. The efficacy of 5l was tested in C57BL/6 mice with GMCSF-secreting B16 tumors, where 1-MT had previously shown activity. Results showed that the dose-dependent inhibition of tumor growth was linked to increasing exposures of 5l in plasma. In addition, a maximal effect of 50% tumor growth control (TGC) was observed when 5l was subcutaneously administered at 75 mg/kg bid. For comparison, 1-MT showed around 45% TGC when administered as subcutaneous pellets [1].
Clinical trial: Up to now, IDO-IN-1 is still in the preclinical development stage.
Reference:
[1] Yue EW, et al. Discovery of potent competitive inhibitors of indoleamine 2,3-dioxygenase with in vivo pharmacodynamic activity and efficacy in a mouse melanoma model. J Med Chem. 2009 Dec 10;52(23):7364-7.