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| Targets |
CC214-2 targets the mammalian target of rapamycin (mTOR), a serine/threonine kinase that exists in two distinct complexes, mTORC1 and mTORC2. It inhibits both complexes, blocking mTORC1-mediated phosphorylation of S6 (pS6) and mTORC2-mediated phosphorylation of Akt at Ser473 (pAktS473). This dual inhibition distinguishes it from rapamycin, which only inhibits a subset of mTORC1 functions.
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| ln Vitro |
In vitro, CC214-2 has been shown to suppress rapamycin-resistant mTORC1 signaling and effectively block mTORC2 signaling. It significantly inhibits the growth of glioblastoma cells. The compound's ability to inhibit both mTOR complexes in cell-based assays confirms its role as a potent and selective mTOR kinase inhibitor. It also induces autophagy in cells.
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| ln Vivo |
In PC3 tumor xenograft models, CC214-2 (25 mg/kg, 50 mg/kg; buccal; once daily for 21 days) reduces tumor volume [1]. U87EGFRvIII flank xenograft growth in mice was significantly reduced by CC214-2 (30 mg/kg, 100 mg) CC214-2 (30 mg/kg; wall) in addition to reducing foam foam CFU and preventing numbers CC214-2 (50 mg/kg; sidewall; once daily for 6 days) [2].
In vivo, CC214-2 has demonstrated efficacy in inhibiting the growth of glioblastomas, particularly in tumors with enhanced sensitivity due to EGFRvIII expression or PTEN loss. In PC3 tumor xenograft models, oral administration of CC214-2 at doses of 25 mg/kg and 50 mg/kg once daily for 21 days reduces tumor volume. These results confirm its oral activity and antitumor efficacy in animal models. |
| Enzyme Assay |
The in vitro activity of CC214-2 against mTOR kinase is typically assessed using cell-free kinase assays. In these assays, the mTOR enzyme (or mTORC1/C2 complexes) is incubated with its substrate and ATP in the presence or absence of varying concentrations of the compound. The phosphorylation of the substrate is then measured, and the IC50 is calculated. For cellular target engagement, the inhibition of pS6 and pAktS473 is measured by Western blot.
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| Cell Assay |
The in vitro cellular activity of CC214-2 is evaluated by treating cancer cell lines with the compound and measuring its effects on cell viability, proliferation, and signaling pathways. Cells are treated with various concentrations of CC214-2, and the levels of phosphorylated S6 (pS6) and phosphorylated Akt (pAktS473) are assessed by Western blot to confirm target inhibition. Cell proliferation is measured using standard assays such as MTT or CellTiter-Glo.
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| Animal Protocol |
Animal/Disease Models: Mouse U87EGFRvIII flank xenografts [2] (100 mg/kg; lateral wall; every 2 days for 6 days) inhibits mTORC1 and mTORC2 signaling in an intracranial astroblastoma model [2]. 50 mg/kg
Route of Administration: Oral; one time/day for 6 days Experimental Results: Inhibition of tumor growth. Autophagy was similarly activated in U87EGFRvIII xenografts. The in vivo efficacy of CC214-2 is evaluated in xenograft mouse models. In these studies, human tumor cells are implanted subcutaneously into immunodeficient mice. When tumors are established, the animals are treated with CC214-2 via oral gavage. Tumor growth is monitored by caliper measurements. At the end of the study, tumors are harvested and analyzed for markers of mTOR pathway inhibition and apoptosis. |
| ADME/Pharmacokinetics |
Dosing in animal models is typically oral, as CC214-2 is orally active. The compound is formulated in a suitable vehicle for oral administration. Pharmacokinetic studies would measure its absorption, distribution, metabolism, and excretion. Its favorable oral bioavailability supports its development as a therapeutic agent. The compound has a molecular weight of 383.44.
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| Toxicity/Toxicokinetics |
The safety and toxicity of CC214-2 would be assessed in standard preclinical toxicology studies. As an mTOR inhibitor, its toxicity profile would be related to its mechanism of action, which affects cell growth and metabolism. These studies are essential for determining its therapeutic index and identifying any potential adverse effects before clinical trials.
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| References |
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| Additional Infomation |
CC214-2 is an oral, selective mTOR kinase inhibitor that targets both mTORC1 and mTORC2. It has shown preclinical efficacy in inhibiting glioblastoma growth and inducing autophagy. It is also being investigated for its potential in host-directed therapy for tuberculosis. As a research compound, it is not an approved drug but represents a promising strategy for targeting the mTOR pathway in cancer and infectious diseases.
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| Molecular Formula |
C20H25N5O3
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|---|---|
| Molecular Weight |
383.444204092026
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| Exact Mass |
383.195
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| CAS # |
1228012-18-7
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| PubChem CID |
58298312
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| Appearance |
Light yellow to light brown solid powder
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| LogP |
0.5
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
28
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| Complexity |
554
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O1CCC(CN2C3C(=NC=C(C4=CN=C(C=C4)C(C)(C)O)N=3)NC(C2)=O)CC1
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| InChi Key |
UWUPKVZQISLSSA-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H25N5O3/c1-20(2,27)16-4-3-14(9-21-16)15-10-22-18-19(23-15)25(12-17(26)24-18)11-13-5-7-28-8-6-13/h3-4,9-10,13,27H,5-8,11-12H2,1-2H3,(H,22,24,26)
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| Chemical Name |
2-[6-(2-hydroxypropan-2-yl)pyridin-3-yl]-8-(oxan-4-ylmethyl)-5,7-dihydropyrazino[2,3-b]pyrazin-6-one
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| Synonyms |
CC214 2; CC214-2; CC2142
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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 |
| 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 : ~12.5 mg/mL (~32.60 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (3.26 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.25 mg/mL (3.26 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6080 mL | 13.0398 mL | 26.0797 mL | |
| 5 mM | 0.5216 mL | 2.6080 mL | 5.2159 mL | |
| 10 mM | 0.2608 mL | 1.3040 mL | 2.6080 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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