G6374

G6374 (1 nM - 100 μM; 17 h) causes significant concentration-dependent depletion of endogenous IRE1 protein in AMO1 and KMS27 multiple myeloma cells^[1].
G6374 (1 μM; 1-4 h) exhibits favorable target selectivity in in vitro kinase assays and AMO1 cells, showing inhibition only against a small number of off-target kinases without inducing the intracellular degradation of these off-target kinases^[1].
G6374 (0.1 μM-1 μM; 150-200 h) selectively inhibits cell proliferation in IRE1-dependent OPM2, AMO1, and KMS27 cancer cell lines, but shows no such activity in non-IRE1-dependent cell lines including U2OS and Colo201^[1].
G6374 (3 μM) verifies its degradation mechanism in AMO1 cells. Its degradation effect can be blocked by the addition of E1 ubiquitin-activating enzyme inhibitors, Neddylation inhibitors, and proteasome inhibitors (Bortezomib (HY-10227)), but not by lysosome inhibitors^[1].
G6374 (3 μM; 2 h) induces ubiquitination in AMO1 cells, significantly increasing the K48-linked ubiquitination level of endogenous IRE1^[1].
G6374 (0.2 μM; 5-60 min) drives direct ubiquitin transfer in a cell-free reconstituted system in vitro, promoting K48-linked polyubiquitination of recombinant IRE1.KR protein by the CRL2^VHL complex, with K704 and K717 as the major modification sites^[1].
G6374 (1-10 μM; 2 h) exhibits protein interaction-inducing activity in AMO1 and HEK293T cells, and significantly promotes the stable association between IRE1 and VHL^[1].
G6374 (0.1 nM-100 μM; 2 h) exerts an interaction interface-dependent effect in HEK293T cells expressing mutant IRE1. Disruption of the G6374-IRE1 binding interface or the IRE1-VHL protein interaction interface (such as the H579A mutation) abolishes G6374-induced interaction and protein degradation^[1].
G6374 (0.3 μM; 2 h) exhibits degradation activity in HEK293T cells expressing monomeric IRE1 mutants (E621A, E836A)^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. .