2-(2H-benzo[b][1,4]oxazin-4(3H)-yl)-N-benzyl-5,6,7,8-tetrahydroquinazolin-4-amine

Description

ML241 (1346528-06-0) is a potent and selective p97 AAA ATPase inhibitor, IC50=100 nM. Inhibits degradation of a p97-dependent but not p97-independent proteasome substrate in a dual-reporter cell line.1?It impairs the endoplasmic reticulum-associated degradation (ERAD) pathway.1?ML241 and related inhibitors (DBeQ for example) have differential responses to p97 mutants as well as the presence of cofactors suggesting the possibility of context-dependent p97 inhibitors.2,3

Uses

2-(2H-Benzo[b][1,4]oxazin-4(3H)-yl)-N-benzyl-5,6,7,8-tetrahydroquinazolin-4-amine is a p97 ATPase inhibitor.

in vitro

previous study showed that both ml241 and its analog ml240 were able to inhibit p97 atpase with ic(50) values of around 100 nm. both ml241 and ml240 could inhibit degradation of a p97-dependent but not a p97-independent proteasome substrate in a dual-reporter cell line. in addition, both ml241 and ml240 could impair the endoplasmic-reticulum-associated degradation (erad) pathway. unexpectedly, ml240 could potently stimulate the accumulation of lc3-ii within minutes, inhibit cancer cell growth, and mobilize the executioner caspases 3 and 7 rapidly, whereas ml241 could not [1].

IC 50

100 nm

References

1) Chou?et al.?(2013),?Structure-activity relationship study reveals ML240 and ML241 as potent and selective inhibitors of p97 ATPase; Chem. Med. Chem.,?8?297 2) Chou?et al.?(2014)?Specific inhibition of p97/VCP ATPase and kinetic analysis demonstrate interaction between D1 and D2 ATPase domains; J. Mol. Biol.?426?2886 3) Fang?et al. (2015)?Evaluating p97 inhibitor analogues for their domain selectivity and potency against the p97-p47 complex; Chem. Med. Chem.?10?52

Raw materials

Preparation Products