| Identification | Back Directory | [Name]
Pyrazino[2,3-b]pyrazin-2(1H)-one, 3,4-dihydro-6-[6-(1-hydroxy-1-methylethyl)-3-pyridinyl]-4-[(tetrahydro-2H-pyran-4-yl)methyl]- | [CAS]
1228012-18-7 | [Synonyms]
CC214-2
Pyrazino[2,3-b]pyrazin-2(1H)-one, 3,4-dihydro-6-[6-(1-hydroxy-1-methylethyl)-3-pyridinyl]-4-[(tetrahydro-2H-pyran-4-yl)methyl]- | [Molecular Formula]
C20H25N5O3 | [MOL File]
1228012-18-7.mol | [Molecular Weight]
383.44 |
| Chemical Properties | Back Directory | [Boiling point ]
569.8±60.0 °C(Predicted) | [density ]
1.39±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO : 12.5 mg/mL (32.60 mM; ultrasonic and warming and heat to 80°C) | [form ]
Solid | [pka]
13.67±0.29(Predicted) | [color ]
Light yellow to light brown |
| Hazard Information | Back Directory | [Uses]
CC214-2 is an oral active and selective mTOR kinase inhibitor. CC214-2 targets to both of mTORC1 (pS6) and mTORC2 (pAktS473). CC214-2 induces autophagy, which is a potential target for host-directed therapy (HDT) in tuberculosis. CC214-2 exhibits synergistic bactericidal and sterilizing activity agasinst tuberculosis (TB), and shortens the treatment duration. CC214-2 also inhibits Rapamycin (HY-10219)-resistant signaling and the growth of glioblastomas in vitro and in vivo[1][2]. | [in vivo]
CC214-2 (25 mg/kg, 50 mg/kg; po; once daily for 21 days) results tumor volume reductions in PC3 tumor xenograft model[1].
CC214-2 (30 mg/kg, 100 mg/kg; po; single dose) inhibits both mTORC1 (pS6) and mTORC2 (pAktS473) in vivo for at least 8 and 24 h, respectively[1].
CC214-2 (30 mg/kg; po) reduces M. tuberculosis CFU numbers and prevents mortality in mice with Chronic M. tuberculosisinfection[1].
CC214-2 (50 mg/kg; po; once daily for 6 days) significantly reduces the growth of mouse U87EGFRvIII flank xenografts[2].
CC214-2 (100 mg/kg; po; once every 2 days for 6 days) inhibits mTORC1 and mTORC2 signaling in an intracranial glioblastoma model[2].
| Animal Model: | U87EGFRvIII flank xenografts in mice[2] | | Dosage: | 50 mg/kg | | Administration: | PO; once daily for 6 days | | Result: | Inhibited tumor growth.
Similarly activated autophagy in U87EGFRvIII xenografts. |
| [IC 50]
mTORC1; mTORC2 | [storage]
Store at -20°C | [References]
[1] Gini B, et al. The mTOR kinase inhibitors, CC214-1 and CC214-2, preferentially block the growth of EGFRvIII-activated glioblastomas. Clin Cancer Res. 2013 Oct 15;19(20):5722-32. DOI:10.1158/1078-0432.CCR-13-0527
[2] Tasneen R, et al. Dual mTORC1/mTORC2 Inhibition as a Host-Directed Therapeutic Target in Pathologically Distinct Mouse Models of Tuberculosis. Antimicrob Agents Chemother. 2021;65(7):e0025321. DOI:10.1128/AAC.00253-21 |
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