Orludodstat (BAY2402234) is a novel potent, selective, orally bioavailable DHODH inhibitor with IC50 of 1.2 nM (human full-length DHODH).
BAY2402234 binds the ubiquinone binding site of DHODH between the N-terminal helices.
BAY2402234 causes dose-dependent upregulation of CD11b with EC50s of 3.16 nM in MOLM-13 cells and 0.96 nM in HEL cells, inhibits the proliferation of THP-1 cells with an IC50 of 2.6 nM, as well as nine other leukemia cell lines representing diverse AML subtypes (IC50=0.08-8.2 nM).
BAY 2402234 shows monotherapy efficacy and differentiation induction across multiple AML subtypes both in vitro and in vivo.
