NTRC 3531-0 is a brain-penetrable, selective inhibitor of L-tryptophan-catabolizing enzyme tryptophan 2,3-dioxygenase (TDO) with IC50 of 490 nM (hTDO) in biochemical assays and cellular IC50 of 816 nM in HEK-hTDO.
NTRC 3531-0 is inactive on hIDO1 in the biochemical assay at >30 uM, inhibits Trp metabolism in human IDO1-overexpressing HEK-293 cells (HEK-hIDO1) with an IC50 of 20.7 µM, 60 times selective for hTDO over hIDO1.
NTRC 3531-0 is slightly less potent on mTDO compared to hTDO in the biochemical assays (mTDO IC50=846 nM).
Oral administration of NTRC 3531-0 (100 mg/kg) resulted in an increase in the concentration of Trp in plasma as well as in brain compared to mice treated with vehicle.
NTRC 3531-0 treatment showed decreased expression of rotenone‐induced glial fibrillary acidic protein (GFAP), which is a marker of enteric glial cells, and decreased α‐synuclein accumulation in the enteric plexus.