ml162

ML162 is a covalent glutathione peroxidase 4 (GPX4) inhibitor that induces ferroptosis. ML162 has antitumor activity and selectively inhibits cell lines expressing mutant RAS oncogenes.

ML162-yne is an effective GPX4 inhibitor and affinity probe containing an alkyne group capable of click chemistry reactions with azide-containing molecules.

LOC1886 is a covalent inhibitor of GPX4, with slightly lower potency compared to RSL3 and ML162.

UAMC-4821 is a ferroptosis inhibitor with an IC50 of 5.2 nM. It effectively scavenges free radicals, inhibits lipid peroxidation, and prevents ML162-induced ferroptosis, providing protective effects on HT-1080 cells. With favorable pharmacokinetic properties in mice, UAMC-4821 presents an oral bioavailability of 63% and demonstrates blood-brain barrier permeability.

GPX4-AUTAC is an autophagy-mediated degrader (AUTAC) targeting GPX4. It consists of the inhibitor ML162-yne, a degradation tag FBnG, and a glycol linker. GPX4-AUTAC facilitates the ubiquitination of GPX4 by the E3 ligase TRAF6 and enhances its interaction with GPX4 and p62, leading to selective autophagy-dependent degradation of GPX4. This compound significantly induces ferroptosis and demonstrates potent anticancer activity in breast cancer cells, patient-derived organoids (PDOs), and MDA-MB-231 tumor xenograft mouse models. It shows strong synergy when used in combination with Sulfasalazine (SAS) or chemotherapy drugs (Paclitaxel or Cisplatin).