ML-240

ML-240 is an ATP-competitive inhibitor of the D2 domain of the p97 ATPase (IC₅₀ = 110 nM). It disrupts the endoplasmic reticulum-associated degradation and autophagy pathways, preventing the degradation of p97-dependent proteasome substrates (IC₅₀ = 0.9 µM) and causing accumulation of ubiquitin conjugates in nuclear membrane and cytosolic compartments at 5-10 µM. ML-240 has also been shown to block proliferation of HCT15 and SW403 colon cancer cell lines (GI₅₀s = 0.76 and 0.5 µM, respectively) and to rapidly mobilize caspase-3 and -7, inducing apoptosis.