ATG-042

ATG-042 is an orally administered, small molecule inhibitor that selectively targets protein arginine methyltransferase 5 (PRMT5) in tumors with methylthioadenosine phosphorylase (MTAP) deletion. Developed by Antengene Corporation, it is designed to exploit synthetic lethality in MTAP-null cancers by inhibiting PRMT5 activity specifically in these tumor cells while sparing healthy tissue. Preclinical studies have demonstrated potent and selective anti-proliferative effects on MTAP-null cell lines (IC50 values between 10 nM and 100 nM), high permeability, good metabolic stability, low risk of drug-drug interactions, high oral bioavailability across species (mice, rats, dogs), and significant brain penetrability. In vivo models showed robust tumor growth inhibition without notable toxicity or weight loss. The compound has shown potential synergy with other antitumor agents and is poised to enter clinical development for cancer indications[2][3][4][5].