TRAIL Upregulation by TIC10 Analogs

Project Summary/Abstract TIC10 (ONC201) is a first-in-class antitumor agent and small molecule inducer of the TRAIL gene which was identified in a high-throughput small molecule library screen in the lab of our collaborator, Dr. Wafik El-Deiry at Penn State University and has been shown to have preclinical efficacy in several difficult-to-treat disease settings that include unmet clinical needs such as glioblastoma and triple-negative breast cancer. The motivation for developing the small molecule TIC10 andanalogs is to overcome efficacy-limiting properties of recombinant TRAIL and to optimize advantages TIC10 that have been demonstrated (Allen et al, 2013), including: (i) longer half-life, (ii) prolonged elevation of serum TRAIL, (iii) a bystander effect through normal cell TRAIL production, (iv) stimulation of TRAIL and death receptor expression, and other properties that are only obtained by a small molecule, such as (v) stability, (vi) cost, (vii) oral activity, and (viii) ability to cross the blood-bra