CC-115 hydrochloride |
| カタログ番号GC34121 |
CC-115 塩酸塩は、それぞれ 13 nM と 21 nM の IC50 を持つ強力なデュアル DNA-PK および mTOR キナーゼ阻害剤です。 CC-115 は、mTORC1 と mTORC2 シグナル伝達の両方をブロックします。
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1300118-55-1
Sample solution is provided at 25 µL, 10mM.
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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.
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].
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[1].
[1]. 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.
Kinase experiment: | An HTR-FRET substrate phosphorylation assay is employed for mTOR kinase. PI3Kα IC50 determinations are outsourced using the mobility shift assay format. Compounds (e.g., CC-115) are assessed against concentrations of ATP at approximately the Km for the assay, with average ATP Km of 15 μM and 50 μM for the mTOR and PI3K assays, respectively[1]. |
Cell experiment: | PC-3 cells are cultured in growth media. For biomarker studies cells are treated for 1 h and then assayed for pS6 and pAkt levels using MesoScale technology. For proliferation experiments, cells are treated with compound (e.g., CC-115) and then allowed to grow for 72 h. All data are normalized and represented as a percentage of the DMSO-treated cells. Results are then expressed as IC50 values[1]. |
Animal experiment: | Mice[1]Encouraged by the observed exposures, CC-115 is advanced into single dose PK/PD studies assessing mTOR pathway biomarker inhibition in tumor bearing mice. PC-3 tumor-bearing mice are administered with a single dose of CC-115, dosed orally at either 1 or 10 mg/kg, and plasma and tumor samples are collected at various time points for analysis. Significant inhibition of both mTORC1 (pS6) and mTORC2 (pAktS473) is observed for all compounds and the level of biomarker inhibition correlated to plasma compound levels. |
References: [1]. 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. | |
| Cas No. | 1300118-55-1 | SDF | |
| Canonical SMILES | [H]Cl.O=C1CN=C2C(N1CC)=NC(C3=C(C)N=C(C4=NN=CN4)C=C3)=CN2 | ||
| Formula | C16H17ClN8O | M.Wt | 372.81 |
| 溶解度 | DMSO : ≥ 30 mg/mL (80.47 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.6823 mL | 13.4117 mL | 26.8233 mL |
| 5 mM | 0.5365 mL | 2.6823 mL | 5.3647 mL |
| 10 mM | 0.2682 mL | 1.3412 mL | 2.6823 mL |
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- Purity: >98.00%
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