CC-115

CC-115 (CAS: 1228013-15-7) is a dual inhibitor targeting both mTOR and DNA-dependent protein kinase (DNA-PK), with reported IC50 values of 21 nM and 13 nM, respectively. mTOR is a critical component of the PI3K/AKT pathway, while DNA-PK plays an essential role in DNA repair processes and genomic stability. In vitro studies demonstrate that CC-115 inhibits CD40(+) IL-21-induced proliferation and can reverse CD40-mediated resistance to fludarabine and venetoclax in chronic lymphocytic leukemia (CLL) cells. It also blocks BCR-mediated signaling in CLL samples resistant to idelalisib. Preclinical in vivo investigations reveal favorable oral bioavailability across multiple species. Early clinical findings suggest potential utility in CLL, particularly in cases with ATM deletions or mutations.

References:

[1] Thijssen R,et al. Dual TORK/DNA-PK inhibition blocks critical signaling pathways in chronic lymphocytic leukemia. Blood.2016 Jul 28;128(4):574-83.

[2] Mortensen DS, et al. Optimization of a Series of Triazole Containing Mammalian Target of Rapamycin (mTOR) Kinase Inhibitors and the Discovery of CC-115. J Med Chem. 2015 Jul 23;58(14):5599-5608.