CC-115 hydrochloride 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.

Product information

CAS Number: 1300118-55-1

Molecular Weight: 372.81

Formula: C16H17ClN8O

Chemical Name: 1-ethyl-7-[2-methyl-6-(4H-1,2,4-triazol-3-yl)pyridin-3-yl]-1H,2H,3H,5H-[1,4]diazino[2,3-b]pyrazin-2-one; chlorohydrogen

Smiles: Cl.CC1N=C(C=CC=1C1=CNC2=NCC(=O)N(CC)C2=N1)C1NC=NN=1

InChiKey: RDIPJCOMBMBHJF-UHFFFAOYSA-N

InChi: InChI=1S/C16H16N8O.ClH/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);1H

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : ≥ 30 mg/mL (80.47 mM).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

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).

In Vivo:

CC-115 hydrochloride 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.

References:

1. Thijssen R, et al. Blood. 2016, 128(4):574-83.
2. Mortensen DS, et al. J Med Chem. 2015, 58(14):5599-608.

Products are for research use only. Not for human use.