Systematic Screening Identifies Dual PI3K and mTOR Inhibition as a Conserved Therapeutic Vulnerability in Osteosarcoma.

Purpose: Osteosarcoma is the most common cancer of bone occurring mostly in teenagers. Despite rapid advances in our knowledge of the genetics and cell biology of osteosarcoma, significant improvements in patient survival have not been observed. The identification of effective therapeutics has been largely empirically based.

Biological evaluation of ent-narciclasine, ent-lycoricidine, and certain enantiomerically-related congeners.

The non-natural enantiomeric forms of narciclasine and lycoricidine ((-)-1 and (-)-2, respectively), as well as congeners 3-6 are available through chemoenzymatic synthesis. Accordingly, they have now been tested for their cytotoxic effects in a 13-member human cancer cell-line panel and found to be only weakly active. In contrast, an authentic sample of the natural enantiomeric form of narciclasine ((+)-1) was found to be highly active in the same screens.