•Since
activation of the unfolded protein response (UPR) via IRE1α
and/or
IRE1β
kinase
promotes key cellular response to endoplasmic reticulum (ER) stress, inhibition
of IRE1α/IRE1β
activity
has critical therapeutic implications in various UPR related and
cell-degenerative diseases such as
•diabetes,
cancer, fibrosis, asthma, and retinitis pigmentosa..
•A
novel series of compounds for selectively regulating IRE1α
or
IRE1β
activity
were identified.
•Potent,
selective and orally bioavailable IRE1α/IRE1β
inhibitors.