MG-002 is a potent, second-generation, orally bioavailable eIF4A RNA helicase inhibitor, potently inhibits cap-dependent mRNA translation with IC50 of 43 nM.
MG-002 stabilizes eIF4A1-RNA complexes, preferentially inhibits mRNAs with polypurine leader regions, and is a potent inhibitor of translation in vitro and in cellula.
MG-002 exhibits cell viability EC50 of 1-10 nM against TNBC lines (4T1, MDA-MB-231) and ER+/HER2+ breast cancer (BT474), which is more potent anti-neoplastic activity than eFT226.
MG-002 is primarily exerting its cytotoxic effects through eIF4A1/2 engagement.
MG-002 (0.5 mg/kg, oral) more significantly impaired mammary tumor growth compared to eFT226 in 4T1-526 tumors models, inhibited primary TNBC tumor growth through reduced cell proliferation and increased apoptosis.
