4-Quinazolinamine, 2-chloro-N-(4-methoxyphenyl)-N-methyl-

Biological Activity

ec50: 2 nm for caspase activationmpi-0441138 is an inducer of apoptosis and growth inhibition.apoptosis or programmed cell death is a process that organisms use to eliminate excessive cells and to control cell numbers. caspases, a family of cysteine proteases, plays a critical role for the initiation as well as execution of apoptosis.

in vitro

mpi-0441138 was identified as a highly active inducer of apoptosis and as a potent inhibitor of cell proliferation in t47d cells. mpi-0441138 also inhibited tubulin polymerization and was effective in cells overexpressing abc transporter pgp-1. it was found that the methyl group on the nitrogen linker was critical for the apoptosis-inducing activity [1].

in vivo

mpi-0441138 could inhibit tumor growth dose-dependently and produced >95% tumor growth inhibition with once weekly dosing at 10 mg/kg and was well tolerated. the maximum tolerated dose of mpi-0441138 was determined to be 25 mg/kg when dosed once weekly, resulting in a good therapeutic index of 2.5. in addition, mpi-0441138 at a dose of 2.5 mg/kg could produce 90% tumor growth inhibition in the mx-1 model when dosed once every day for 5 days for 2 weeks. furthermore, in nude mice, mpi-0441138 significantly inhibited the growth of human pc-3 prostate cancer xenografts [1].

References

[1] n. sirisoma, s. kasibhatla, a. pervin, et al. discovery of 2-chloro-n-(4-methoxyphenyl)-n-methylquinazolin-4-amine (ep128265, mpi-0441138) as a potent inducer of apoptosis with high in vivo activity. journal of medicinal chemistry 51, 4771-4779 (2008).

Raw materials

Preparation Products