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| 25mg |
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| 50mg |
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| 100mg |
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Purity: ≥98%
CC-115 hydrochloride (CC115 HCl) is a novel and potent dual inhibitor of DNA-PK (DNA-dependent protein kinase) and mTOR (mammalian target of rapamycin) with IC50s of 13 nM and 21 nM, respectively and with potential antineoplastic activity. According to reports, CC-115 has the ability to reverse CD40-mediated resistance to fludarabine and venetoclax as well as the proliferation caused by CD40(+) interleukin-21 stimulation. Additionally, CC-115 and CLL samples from patients who had developed resistance to idelalisib treatment inhibited BCR-mediated signaling.
| Targets |
DNA-PK (IC50 = 13 nM); mTOR (IC50 = 21 nM); mTORC1; mTORC2; PI3Kα (IC50 = 852 nM)
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| ln Vitro |
CC-115 inhibits PC-3 cells proliferation with an IC50 of 138 nM. Only one kinase other than mTOR kinase is identified with more than 50% inhibition in a kinase selectivity assessment against a panel of 250 protein kinases at 3 μM (cFMS 57%, IC50=2.0 μM). The remaining PI3K related kinases (PIKKs) tested include PI3K-alpha (IC50=0.85 μM), ATR (50% inhibition at 30 μM), and ATM (IC50>30 μM). Of the PI3K related kinases (PIKKs) tested, CC-115 exhibits 40 to >1000 fold selectivity against the remaining PIKKs. The inhibitory concentrations (IC50) of CC-115 for a panel of CYP enzymes are >10 μM and >33 μM, respectively, for the hERG (human ether-a-go-go-related gene) ion channel[1].
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| ln 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. Lower doses of CC-115, such as 0.25, 0.5, and 1 mg/kg bid or 1 mg/kg qd, are tested, and tumor volume reductions of 46%, 57%, 66%, and 57%, respectively, are seen. The inhibition of CC-115 lasts for 24 hours. At a dose of 1 mg/kg, CC-115 exhibits significant inhibition at 1 and 3 hours, continuing to exhibit inhibition at 10 hours. Both a once-daily (qd) and twice-daily (bid) dosing schedule is used to evaluate CC-115[1].
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| Enzyme Assay |
An HTR-FRET substrate phosphorylation assay is employed for mTOR kinase. The mobility shift assay format is used to outsource the determination of PI3K'sIC50. Compounds (such as CC-115) are evaluated in comparison to ATP concentrations at approximately the Km for the assay, with average ATP Km values of 15 M and 50 M for the mTOR and PI3K assays, respectively[1].
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| Cell Assay |
In growth media, PC-3 cells are cultured. In order to measure the levels of pS6 and pAkt, cells are treated for 1 hour for biomarker studies. For experiments on cell proliferation, cells are given a substance (like CC-115) and then allowed to grow for 72 hours. All data are normalized and shown as a percentage of the cells that received DMSO treatment. The IC50 values of the results are then presented[1].
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| Animal Protocol |
Mice: Encouraged by the exposures seen, CC-115 has advanced into single dose PK/PD studies evaluating the inhibition of the mTOR pathway biomarker in tumor-bearing mice. Plasma and tumor samples are taken at various time points for analysis after PC-3 tumor-bearing mice are given a single dose of CC-115, dosed orally at either 1 or 10 mg/kg. The level of biomarker inhibition is correlated with plasma compound levels, and significant inhibition of both mTORC1 (pS6) and mTORC2 (pAktS473) is seen for all compounds.
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| References |
| Molecular Formula |
C₁₆H₁₇CLN₈O
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|---|---|---|
| Molecular Weight |
372.81
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| Exact Mass |
372.121
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| CAS # |
1300118-55-1
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| Related CAS # |
CC-115;1228013-15-7
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| PubChem CID |
67153895
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| Appearance |
Light yellow to yellow solid
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
26
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| Complexity |
491
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| Defined Atom Stereocenter Count |
0
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| SMILES |
[H]Cl.O=C1CN=C2C(N1CC)=NC(C3=C(C)N=C(C4=NN=CN4)C=C3)=CN2
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| InChi Key |
RDIPJCOMBMBHJF-UHFFFAOYSA-N
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| InChi Code |
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
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| Chemical Name |
5-ethyl-3-[2-methyl-6-(1H-1,2,4-triazol-5-yl)pyridin-3-yl]-7,8-dihydropyrazino[2,3-b]pyrazin-6-one;hydrochloride
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| Synonyms |
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: >67 mg/mL (199.2 mM)
Water: N/A Ethanol: N/A |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (268.23 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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