Cancer

In vitro, mouse and pig studies identified an RXR agonist that could help treat soft tissue sarcoma (STS). In silico screening of a small molecule library for compounds predicted to bind RXR, followed by chemical synthesis and testing of hits in two pig sarcoma cell lines, yielded a bisindolylmethane-based compound that, when loaded into nanoparticles, was cytotoxic with IC₅₀ values of 44 µM and 38 µM. The IC₅₀ values of the free compound were not reported. In a xenograft mouse model of STS, the free compound or nanoparticles loaded with the compound increased survival and decreased tumor volume compared with vehicle or no treatment. In a pig model of STS expressing the oncogenic KRAS G12D and p53 R167H mutations, the free compound or the compound-loaded nanoparticles decreased tumor volume compared with vehicle, and the agents increased levels of an RXR-induced gene signature in the liver compared with no treatment. Next steps include testing the compound in dog models of sarcoma.

Eisai Co. Ltd., Bausch Health Companies Inc. and Minophagen Pharmaceutical Co. Ltd. market Targretin bexarotene, an oral RXR agonist, for cutaneous T cell lymphoma (CTCL)...