BioCentury
ARTICLE | Distillery Therapeutics

Cancer

December 13, 2016 8:01 PM UTC

Cell culture and mouse studies suggest combining Ridaura auranofin and glutathione synthesis inhibitors with RIPK1 or MLKL inhibitors could help treat tuberous sclerosis complex-associated tumors, which are caused by loss-of-function mutations in the TSC1/TSC2 complex. In mouse embryonic fibroblast and human angiomyolipoma TSC2-knockout cell lines, Ridaura plus a glutathione synthesis inhibitor tool compound decreased viability and increased cell death compared with either agent alone, and increased necrosis compared with no treatment. In the cell lines treated with Ridaura and the glutathione synthesis inhibitor, co-treatment with inhibitor tool compounds against RIPK1 or MLKL increased cell death compared with vehicle co-treatment. In a mouse model of tuberous sclerosis complex-associated tumors, Ridaura plus the glutathione synthesis inhibitor decreased tumor growth compared with vehicle. Also in the model, the combination of Ridaura, the glutathione synthesis inhibitor and the RIPK1 inhibitor increased the number of necrotic cells in tumors and decreased tumor growth compared with Ridaura plus the glutathione synthesis inhibitor. Next steps could include testing the combination therapies in additional models of tuberous sclerosis complex-associated tumors.

Nestle S.A. markets Ridaura, an oral formulation of gold salt, to treat rheumatoid arthritis. Nestle and The Leukemia & Lymphoma Society have the compound in Phase I/II testing to treat chronic lymphocytic leukemia (CLL) and preclinical testing to treat mantle cell lymphoma (MCL)...