Through an exhaustive medicinal chemistry campaign, Buto sampled chemical diversity space among >100M NCEs, blanketing the Shc target to find the most effective scaffolds possible. Buto holds multiple patent families around Shc inhibitors (ShcBs) B-105, B-301, and B-401, including composition of matter, methods of use, formulation and analogs.
Excessive fibrosis is responsible for about 40% of health care costs in the developed world. Buto’s molecules have efficacy in multiple animal models of liver fibrosis and NASH, as they inhibit the transition of the Hepatic Stellate Cells (HSCs) that drive fibrosis. In the bleomycin lung fibrosis model, ShcB’s outperform Ofev/Nintedanib. Buto’s molecules have been externally validated by an external pharmaceutical company to reduce fibrosis in human lung tissue.
There are 5M in the US with Alzheimer’s Disease. Shc protein and activity rises in the brains of AD patients, and elimination of Shc ameliorates AD in animal models. Buto’s molecule inhibit the pathophysiological transition of microglia downstream of A-beta deposition, to ameliorate microglial inflammation and preserve memory in two animal models of AD.