Acute
myeloid leukemia (AML) refers to one of the most lethal blood
malignancies worldwide. FLT3-ITD mutation is recognized as the most
common one that predicted a poorer prognosis. There have been many
prominent FLT3-ITD inhibitors approved by the FDA for clinical therapies.
However, as impacted by undesirable off-target effects, differentiated
metabolic issues, and clinical drug resistance problems, it remains
challenging to discover alternative and promising solutions for treating
FLT3-ITD+ AML. In this study, dovitinib was chemically
modified and converted into CRBN-recruiting PROTACs. Two active compounds
were identified, which showed enhanced antiproliferative effects against
FLT3-ITD+ AML cells, both in vitro and in vivo. As demonstrated from further biological evaluation,
the compounds could induce the degradation of the FLT3-ITD and KIT
proteins in a ubiquitin–proteasome-dependent manner and completely
block their downstream signaling pathway. The findings of this study
would provide another promising strategy to develop novel therapies
for FLT3-ITD+ AML.
In this study, a robust and facile method for desulfonation to achieve secondary amines was demonstrated. Diphenylphosphine was exhibited to significantly expedite the cleavage of sulfonamides under basic conditions. Aromatic...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.