CC-115

Cas No.:	1228013-15-7
Chemical Name:	Cc-115
Synonyms:	CC-115;CC 115;FII75TFH5L;1-ethyl-7-(2-methyl-6-(1H-1,2,4-triazol-5-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one;1-Ethyl-7-(2-methyl-6-(4H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one;GMYLVKUGJMYTFB-UHFFFAOYSA-N;Pyrazino(2,3-b)pyrazin-2(1H)-one, 1-ethyl-3,4-dihydro-7-(2-methyl-6-(1H-1,2,4-triazol-5-yl)-3-pyridinyl)-;1-Ethyl-7-(2-methyl-6-(4H-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino(2,3-b)pyrazin
SMILES:	O=C1C([H])([H])N([H])C2C(=NC(=C([H])N=2)C2C([H])=C([H])C(C3=NC([H])=NN3[H])=NC=2C([H])([H])[H])N1C([H])([H])C([H])([H])[H]
Formula:	C16H16N8O
M.Wt:	336.3512
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	CC-115 is a potent and dual DNA-PK and mTOR kinase inhibitor with IC50s of 13 nM and 21 nM, respectively. CC-115 blocks both mTORC1 and mTORC2 signaling.
In Vivo:	CC-115 shows good in vivo PK profiles across multiple species with 53%, 76% and ~100% oral bioavailability in mouse, rat and dog, respectively. CC-115 is tested at lower doses of 0.25, 0.5 and 1 mg/kg bid or 1 mg/kg qd, with observed corresponding tumor volume reductions of 46%, 57%, 66% and 57% respectively. CC-115 sustains inhibition though 24 hours. At the 1 mg/kg dose CC-115 shows significant inhibition at 1 and 3 hours, CC-115 demonstrating inhibition through 10 hours. CC-115 is evaluated using both once (qd) and twice (bid) daily dosing schedules[1].
In Vitro:	CC-115 inhibits PC-3 cells proliferation with an IC50 of 138 nM. In a kinase selectivity assessment against a panel of 250 protein kinases at 3 μM, only one kinase other than mTOR kinase is identified with more than 50% inhibition (cFMS 57%, IC50=2.0 μM). Of the PI3K related kinases (PIKKs) tested, CC-115 proves to be equipotent against DNA PK (IC50=15 nM) and demonstrates 40 to >1000 fold selectivity against the remaining PIKKs tested; PI3K-alpha (IC50=0.85 μM), ATR (50% inhibition at 30 μM) and ATM (IC50>30 μM). The IC50 values for CC-115 are >10 μM against a panel of CYP enzymes and >33 μM for the hERG (human ether-a-go-go-related gene) ion channel. When screened in a single point assay at 10 μM against a Cerep receptor and enzyme panel only one target is inhibited >50% (PDE3, IC50=0.63 μM)[1].