p97 ATPase Inhibitors for Cancer and Neurodegneration
Inhibition of p97 ATPase activity triggers downstream cellular effects, including the suppression of cellular proliferation that makes cancer such a dangerous disease. And because these compounds specifically inhibit p97, they offer the possibility of treating a wide array of ailments with fewer side effects than drugs acting on broader pathways; neurodegenerative diseases, for example, display dysregulation of protein homeostasis via p97 and have the potential to be treated with these inhibitors.
Description
Cancer cells tend to over-produce proteins, but this doesn’t generally get in the way of their growth and proliferation because these cells can rely on built-in molecular cleanup mechanisms — especially p97 ATPase — to maintain a healthy balance. Although recent evidence shows that inhibiting p97 kills cancer cells, there are currently no drugs on the market that target p97 directly. We have discovered potent and specific p97 inhibitors that may lead to new treatments for cancer, and possibly also neurodegeneration and genetic disorders involving p97 mutations. Structural analysis indicates that these compounds bind allosterically to act literally as a “wrench in the works,” blocking the motion of the p97 protein subunits.Applications
• Treatment of cancer by suppressing cellular proliferation• Potential treatment of other diseases that result from dysregulation of p97
Advantages
• Specifically targets p97 ATPase• More efficacious with fewer side effects than other compounds working through similar or related mechanisms