Prodrug 9

Prodrug 9 is an orally bioavailable small molecule prodrug of **MRTX1133**, a potent and selective non-covalent inhibitor of the **KRAS G12D** mutant protein. Developed by **Risen (Shanghai) Pharma Tech**, Prodrug 9 was designed to overcome the poor oral pharmacokinetics and low bioavailability of its parent compound. The molecule features a 1-(butyryloxy)ethyl carbamate promoiety attached to the diazabicyclooctane nitrogen of MRTX1133, which is enzymatically cleaved in vivo to release the active inhibitor. MRTX1133 binds with high affinity to the switch-II pocket of the GDP-bound (inactive) state of KRAS G12D, effectively blocking downstream oncogenic signaling pathways such as the MAPK/ERK cascade. In preclinical studies, Prodrug 9 demonstrated significant tumor growth inhibition in KRAS G12D-mutant xenograft models, particularly in pancreatic cancer models, following oral administration.

Other names

1-(Butyryloxy)ethyl (1R,5S)-3-(7-(8-ethynyl-7-fluoro-3-hydroxynaphthalen-1-yl)-8-fluoro-2-(((2R,7aS)-2-fluorotetrahydro-1H-pyrrolizin-7a(5H)-yl)methoxy)pyrido[4,3-d]pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octane-8-carboxylate