| Identification | Back Directory | [Name]
CC-223 | [CAS]
1228013-30-6 | [Synonyms]
CC-223
7-[6-(2-Hydroxypropan-2-yl)pyridin-3-yl]-1-(trans-4-methoxycyclohexyl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1H)-one | [Molecular Formula]
C21H27N5O3 | [MDL Number]
MFCD28976054 | [MOL File]
1228013-30-6.mol | [Molecular Weight]
397.47 |
| Chemical Properties | Back Directory | [Boiling point ]
562.9±60.0 °C(Predicted) | [density ]
1.37±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
insoluble in H2O; ≥108 mg/mL in DMSO; ≥20.28 mg/mL in EtOH | [form ]
crystalline solid | [pka]
13?+-.0.29(Predicted) | [color ]
Light yellow to yellow |
| Questions And Answer | Back Directory | [Description]
CC-223 is a potent, selective, and orally bioavailable inhibitor of mTOR kinase, demonstrating inhibition of mTORC1 (pS6RP and p4EBP1) and mTORC2 [pAKT(S473)] in cellular systems. After tumor-bearing mice was treated with CC-223 for a single oral dose. It exhibited dose-dependent tumor growth inhibition in multiple solid tumor xenografts. The observed antitumor activity of CC-223 is likely to be mediated through inhibition of both mTORC1 and mTORC2. CC-223 is currently in phase I clinical trials for its treatment of advanced solid and hematologic cancers.
| [References]
Varga, Andrea, et al. "Phase I expansion trial of an oral TORC1/TORC2 inhibitor (CC-223) in advanced solid tumors." Journal of Clinical Oncology 31.15(2013):-.
Mortensen, D. S., et al. "CC-223, a Potent and Selective Inhibitor of mTOR Kinase: In Vitro and In Vivo Characterization." Molecular Cancer Therapeutics 14.6(2015):1295.
Goy, A, et al. "Phase I expansion trial of an oral TORC1/TORC2 inhibitor (CC-223) in diffuse large B-cell lymphoma (DLBCL) and multiple myeloma (MM)." Neuroendocrinology 43.3(2013):276-276.
Shih, Kent C, et al. "Phase I trial of an oral TORC1/TORC2 inhibitor (CC-223) in advanced solid and hematologic cancers." Journal of Clinical Oncology (2012).
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| Hazard Information | Back Directory | [Uses]
Onatasertib (CC-223) is a potent, selective, and orally bioavailable inhibitor of mTOR kinase, with an IC50 value for mTOR kinase of 16 nM. Onatasertib inhibits both mTORC1 and mTORC2. | [in vitro]
cc-223 was identified as an atp–competitive inhibitor of the mtor kinase targeting mtorc1 of both 4ebp1 and p70 s6 kinase 1 and mtorc2, which prevented the upregulation of akt phosphorylation. moreover, cc-223 was selectively potent to mtor kinase while showed more than 150-fold sensitivity against the related lipid kinase, pi3ka. in addition, cc-223 was active over many non-hodgkin lymphoma cell lines and solid tumor lines such as including glioma, breast, hepatocellular carcinoma, as well as non–small cell lung cancer [1]. | [in vivo]
in animal study, cc-223 was selected for evaluation in pc-3 tumor bearing efficacy mouse models. mice were orally treated with vehicle or various doses of cc-223 once daily or twice daily at a dose of 5 ml/kg for 21 days, and the final reductions of tumor volume were measured following the final day of dosing. results showed that all cc-223 had dose- and schedule-dependent inhibition of tumor growth in the pc-3 model. moreover, the maximum observed efficacy for cc-223 was determined to be 87%, at its tolerated dose of 25 mg/kg q.d. [1]. | [IC 50]
16 nm | [storage]
Store at -20°C |
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