ISR activator-4

ISR activator-4 (Compound A-(S)) stabilises the inhibitory complex between recombinant human eIF2B and phosphorylated eIF2α-NTD with an EC₅₀ of 2.2 μM, reducing the fast-phase dissociation contribution by 82%^[1].
ISR activator-4 binds recombinant human eIF2B with a K_1/2max of 6.4 μM, showing positive cooperative binding with eIF2(αP) (alpha = 0.16) and displacing the ISRIB (HY-12495A) probe ~30-fold more potently than its diastereomer^[1].
ISR activator-4 inhibits the GEF activity of recombinant human eIF2B in an eIF2(αP)-dependent manner, increasing the half-life of GDP-BODIPY bound to eIF2 to 76.42 s^[1].
ISR activator-4 (1 h) binds to the ISRIB-binding site of recombinant human eIF2B, stabilising the complex in the inactive I-state and forming specific interactions with residues across the eIF2B β-δ subunit interface^[1].
ISR activator-4 (18 h) activates the CHOP::GFP ISR reporter in CHO cells with an EC₅₀ of 12.47 μM^[1].
ISR activator-4 (20 μM) inhibits translation initiation in U-2 OS cells, reducing the polysome/monosome ratio, and this effect is reversed by co-treatment with 2 μM ISRIB^[1].

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