At a concentration of 10 μM, MKC9989 completely blocks both basal and thapsigargin-induced splicing of XBP1 mRNA. These effects persist even in cells pre-treated with thapsigargin, suggesting MKC9989's ability to fully reverse XBP1 splicing once the UPR is triggered. Additionally, MKC9989 significantly enhances the stability of the RIDD target CD59 mRNA when co-administered with thapsigargin compared to thapsigargin treatment alone. It also slightly elevates CD59 mRNA levels in unstressed cells, likely due to inhibiting baseline RIDD activity. Unlike its impact on XBP1 splicing, MKC9989 moderately increases CD59 levels when administered 2 hours after thapsigargin treatment. Lastly, MKC9989's effectiveness against XBP1 mRNA splicing (EC50=0.33 μM) is comparable to its potency against RNA cleavage in vitro[1].
体外研究
At a concentration of 10 μM, MKC9989 completely blocks both basal and thapsigargin-induced splicing of XBP1 mRNA. These effects persist even in cells pre-treated with thapsigargin, suggesting MKC9989's ability to fully reverse XBP1 splicing once the UPR is triggered. Additionally, MKC9989 significantly enhances the stability of the RIDD target CD59 mRNA when co-administered with thapsigargin compared to thapsigargin treatment alone. It also slightly elevates CD59 mRNA levels in unstressed cells, likely due to inhibiting baseline RIDD activity. Unlike its impact on XBP1 splicing, MKC9989 moderately increases CD59 levels when administered 2 hours after thapsigargin treatment. Lastly, MKC9989's effectiveness against XBP1 mRNA splicing (EC50=0.33 μM) is comparable to its potency against RNA cleavage in vitro[1].
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