KUS121

KUS121 (Kyoto University Substance 121) is a small molecule that selectively inhibits the ATPase activity of valosin-containing protein (VCP), a member of the AAA (ATPases Associated with diverse cellular Activities) family. VCP is involved in essential cellular processes such as proteasome-mediated protein degradation, endoplasmic reticulum-associated degradation (ERAD), and membrane fusion. Unlike broad VCP inhibitors, KUS121 does not interfere with these vital functions but specifically suppresses ATP consumption by inhibiting VCP’s ATPase activity. This action helps maintain intracellular ATP levels and reduces endoplasmic reticulum (ER) stress, thereby preventing cell death in various pathological conditions. Preclinical studies have demonstrated its protective effects in models of ocular diseases (retinitis pigmentosa, macular degeneration, glaucoma), ischemic diseases (myocardial infarction, stroke), Parkinson’s disease, acute kidney injury, and osteoarthritis. Clinical trials have shown safety and potential efficacy for non-arteritic central retinal artery occlusion when administered intravitreally as a neuroprotective agent.

Other names

KUS-121 free acidKUS121 free acidKUS 121 free acid