CC-115

CC-115 is a dual inhibitor of mammalian target of rapamycin (mTOR) and DNA protein kinase (DNA-PK; IC₅₀s = 0.021 and 0.013 µM, respectively).^1,2 It is selective for mTOR and DNA-PK over PI3Kα, ATM, and ATR (IC₅₀s = 0.85, >30, and >30 µM, respectively). CC-115 inhibits growth in a panel of 123 cancer cell lines, including breast, head and neck, and lung cancer cells (GI₅₀s = 0.015-1.77 µM), and non-homologous end joining (NHEJ) in CAL-51 and MDA-MB-231 breast, PC3 prostate, and HCT116 colon cancer cells (IC₅₀s = 3.15, 2.16, 2.72, and 6.35 µM, respectively).² It reduces tumor growth in a PC3 prostate cancer mouse xenograft model when administered at doses of 0.25, 0.5, and 1 mg/kg twice per day.¹

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1. Mortensen, D.S., Perrin-Ninkovic, S.M., Shevlin, G., 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. 58(14), 5599-5608 (2015).

2. Tsuji, T., Sapinoso, L.M., Tran, T., et al. CC-115, a dual inhibitor of mTOR kinase and DNA-PK, blocks DNA damage repair pathways and selectively inhibits ATM-deficient cell growth in vitro. Oncotarget 8(43), 74688-74702 (2017).