| Stereochemistry | ACHIRAL |
| Molecular Formula | C16H16N8O |
| Molecular Weight | 336.3512 |
| Optical Activity | NONE |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CCN1C(=O)CNC2=C1N=C(C=N2)C3=C(C)N=C(C=C3)C4=NN=CN4
InChI
InChIKey=GMYLVKUGJMYTFB-UHFFFAOYSA-N
InChI=1S/C16H16N8O/c1-3-24-13(25)7-18-15-16(24)22-12(6-17-15)10-4-5-11(21-9(10)2)14-19-8-20-23-14/h4-6,8H,3,7H2,1-2H3,(H,17,18)(H,19,20,23)
| Molecular Formula | C16H16N8O |
| Molecular Weight | 336.3512 |
| Charge | 0 |
| Count |
MOL RATIO
1 MOL RATIO (average) |
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
CC-115 is a recently identified inhibitor of the mammalian Target of Rapamycin Kinase (TORK) and DNA-Dependent Protein Kinase (DNA-PK). It is under investigation in phase II clinical trials for the treatment for Glioblastoma and in phase I trials for the treatment of prostate cancer, Ewing's, Osteosarcoma, Chronic Lymphocytic Leukemia and Squamous Cell Carcinoma of the Head and Neck.
Originator
Approval Year
Cmax
AUC
Sourcing
PubMed
Sample Use Guides
Dose level starts with 0.5mg daily by mouth in cycles of 28 days. Level increases for different patient cohorts in 100% or 50% increments until optimal dose schedule is established for further study. Treatment continues for as long as patient benefits (i.e., until disease progression or unacceptable toxicity).
Route of Administration:
Oral
To determine whether combined inhibition of TORK and DNA-PK induces cell death, there were compared CC-115 (range of concentration from 0.001 until 10 uM) to inhibitors that are more specific: CC-214, CC-292, idelalisisb, and NU7441. To correct for variability in viability between thawed primary chronic lymphocytic leukemia (CLL) samples, specific apoptosis was calculated. CC-214 (TORKi), CC-292 (BTKi), idelalisib (PI3Kδi), and NU7441 (DNAPKi) induced modest cell death (IC50 > 10 µM and maximum induction of apoptosis at 10 µM of 30-40 %. Whereas CC-115 induced cell death with an IC50 of 0.51 µM. Cell death was due to on-target inhibition of TORK and DNA-PK, because the combination of the TORK inhibitor CC-214 and the DNA-PK inhibitor NU7441 resulted in cell death comparable to CC-115. CC-115 induced cell death in clinically relevant prognostic CLL subgroups.
