Wang, Likun published the artcileDivergent allosteric control of the IRE1α endoribonuclease using kinase inhibitors, Product Details of C9H9ClIN3, the main research area is divergent allosteric control IRE1 endoribonuclease kinase.
Under endoplasmic reticulum stress, unfolded protein accumulation leads to activation of the endoplasmic reticulum transmembrane kinase/endoRNase IRE1α. IRE1α oligomerizes, autophosphorylates and initiates splicing of XBP1 mRNA, thus triggering the unfolded protein response (UPR). Here we show that IRE1α’s kinase-controlled RNase can be regulated in two distinct modes with kinase inhibitors: one class of ligands occupies IRE1α’s kinase ATP-binding site to activate RNase-mediated XBP1 mRNA splicing even without upstream endoplasmic reticulum stress, whereas a second class can inhibit the RNase through the same ATP-binding site, even under endoplasmic reticulum stress. Thus, alternative kinase conformations stabilized by distinct classes of ATP-competitive inhibitors can cause allosteric switching of IRE1α’s RNase-either on or off. As dysregulation of the UPR has been implicated in a variety of cell degenerative and neoplastic disorders, small-mol. control over IRE1α should advance efforts to understand the UPR’s role in pathophysiol. and to develop drugs for endoplasmic reticulum stress-related diseases.
Nature Chemical Biology published new progress about Aromatic nitrogen heterocycles Role: BSU (Biological Study, Unclassified), PRP (Properties), SPN (Synthetic Preparation), BIOL (Biological Study), PREP (Preparation) (kinase inhibitors). 1320266-92-9 belongs to class pyrazines, name is 8-Chloro-1-iodo-3-isopropylimidazo[1,5-a]pyrazine, and the molecular formula is C9H9ClIN3, Product Details of C9H9ClIN3.