TIC10 (1616632-77-9) is novel anti-cancer compound that acts via early-stage integrated stress response activation leading to selective cancer cell death.1-3 TIC10 potently activates mitochondrial caseinolytic protease P (ClpP) causing eIF2α-independent induction of ATF4 and Akt/ERK/Foxo3a/DR5/TRAIL-dependent apoptosis.4 Currently in clinical trials.
1) Allen et al. (2013) Dual Inactivation of Akt and ERK by TIC10 Signals Foxo3a Nuclear Translocation, TRAIL Gene Induction, and Potent Antitumor Effects, Sci. Transl. Med. 5 171ra17
2) Allen et al. (2015) Identification of TRAIL-inducing compounds highlights small molecule ONC201/TIC10 as a unique anti-cancer agent that activates the TRAIL pathway, Mol. Cancer. 14 99
3) Allen et al. (2016) Discovery and Clinical Introduction of First-In-Class Imipridone ONC201, Oncotarget 7 74380
4) Ishizawa et al. (2019) Mitochondrial ClpP-Mediated Proteolysis Induces Selective Cancer Cell Lethality, Cancer Cell 35 721