Navlimetostat hydrochloride, also known as MRTX-1719 hydrochloride, is a potent, orally active, selective PRMT5-MTA complex inhibitor (IC50 values of 3.6 nM for PRMT5-MTA and 20.5 nM for PRMT5). It binds strongly to the PRMT5-MTA complex (KD of 0.14 pM) and demonstrates antineoplastic activity in vitro and in vivo, making it suitable for cancer research.
- In vitro activity: Inhibits PRMT5 activity (IC50 8 nM) and viability (IC50 12 nM) in MTAP-deleted HCT116 cells.
- In vivo activity: Significantly reduces tumor growth in Lu-99 orthotopic xenograft models (12.5-100 mg/kg/day, oral, 21 days).
- Pharmacokinetics: High bioavailability in CD-1 mice (80% at 30 mg/kg p.o.) and Beagle dogs (59% at 10 mg/kg p.o.).