1228013-30-6

Basic information

• Product Name: CC-223
• 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
• CAS NO: 1228013-30-6
• Molecular Formula: C21H27N5O3
• Molecular Weight: 397.47078
• Product Categories: Anti-cancer;Inhibitor
• Mol File: 1228013-30-6.mol
• Article Data: 0

Chemical Properties

• Boiling Point: 562.9±60.0 °C(Predicted)
• Appearance: /
• Density: 1.37±0.1 g/cm3(Predicted)
• Solubility: insoluble in H2O; ≥108 mg/mL in DMSO; ≥20.28 mg/mL in EtOH
• PKA: 13?+-.0.29(Predicted)
• CAS DataBase Reference: CC-223(CAS DataBase Reference)
• NIST Chemistry Reference: CC-223(1228013-30-6)
• EPA Substance Registry System: CC-223(1228013-30-6)

Safety Data

• Hazardous Substances Data: 1228013-30-6(Hazardous Substances Data)

Usage

Description

CC-223 is a potent, selective, and orally bioavailable inhibitor of mTOR kinase, which demonstrates inhibition of both mTORC1 (pS6RP and p4EBP1) and mTORC2 (pAKT(S473)) in cellular systems. It has shown to inhibit growth and induce apoptosis in hematologic and solid tumor cell lines in vitro, and exhibits dose-dependent tumor growth inhibition in multiple solid tumor xenografts in vivo. The antitumor activity of CC-223 is likely mediated through the inhibition of both mTORC1 and mTORC2. Currently, CC-223 is in phase I clinical trials for the treatment of advanced solid and hematologic cancers.
Used in Pharmaceutical Industry:
CC-223 is used as an anticancer agent for its ability to inhibit the mTOR pathway, which plays a crucial role in the regulation of cell growth, proliferation, and survival. By targeting both mTORC1 and mTORC2, CC-223 has the potential to treat a wide range of advanced solid and hematologic cancers.
Used in Cancer Research:
CC-223 is used as a research tool for studying the role of the mTOR pathway in cancer development and progression. Its potent and selective inhibition of mTOR kinase allows researchers to investigate the underlying mechanisms of mTOR signaling and its impact on tumor growth and survival.
Used in Drug Development:
CC-223 is used as a lead compound in the development of new drugs targeting the mTOR pathway for cancer treatment. Its high potency, selectivity, and bioavailability make it an attractive candidate for further optimization and improvement to enhance its therapeutic potential and safety profile.

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).

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

references

[1] mortensen ds, et al. discovery of mammalian target of rapamycin (mtor) kinase inhibitor cc-223. j med chem. 2015 jul 9;58(13):5323-5333.[2] bendell jc, et al. a phase i dose-escalation study to assess safety, tolerability, pharmacokinetics, and preliminary efficacy of the dual mtorc1/mtorc2 kinase inhibitor cc-223 in patients with advanced solid tumors or multiple myeloma. cancer. 2015 oct 1;121(19):3481-90.