Rhein is a pan inhibitor of the ALKBH proteins, inhibits ALKBH2, ALKBH3 and FTO with IC50 values of 9.1 μM, 5.3 μM and 21.0 μM, respectively. Rhein also inhibits ALKBH5 with an IC50 value of 9.96 μM. Rhein binds to AlkB repair enzymes in vitro and promotes thermal stability in vivo. Rhein inhibits FTO demethylation of N6-methyladenine in vitro and elevates the level of N6-methyladenine within mRNA in HeLa cells. Rhein efficiently inhibits AlkB without inhibiting the glycosylase AlkA or the methyltransferase Ada in vitro.
