ZY-MY-111 is a selective, reversible, small-molecule inhibitor of interleukin-4-induced-1 (IL4I1, FIG1) with IC50 of 1.86 uM, specifically targets the IL4I1-AHR axis and restores anti-tumor immunity.
ZY-MY-111 displays exceptional selectivity, showing no inhibition of IDO1-mediated tryptophan metabolism at 10 uM.
ZY-MY-111 occupies the enzymatic active site of IL4I1, directly overlapping with the binding regions of endogenous substrates phenylalanine and tryptophan.
ZY-MY-111 dose-dependently suppresses basal AHR activation with IC50 of 2.14 uM in HEK293T-XRE reporter cells.
ZY-MY-111 significantly suppressed L-tryptophan (500 μM)-induced AHR nuclear accumulation, rescued the up-regulation of CYP1A1 expression induced by tryptophan in HT-29 cells.
ZY-MY-111 enhances CD8+ T cell proliferation and antitumor response, exhibits antitumor efficacy through immune reprogramming.
ZY-MY-111 (50 mg/kg, BID, i.p.) significantly suppressed tumor growth in the syngeneic A20 B cell lymphoma mouse model.
ZY-MY-111 (25 mg/kg, BID, i.p.) significantly increased CD8+/CD4+ ratio and infiltration of effector memory T cells in mice bearing CT26 colon carcinoma.