1. PI3K/Akt/mTOR Autophagy
  2. mTOR Autophagy
  3. CC214-2

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.

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CC214-2 Chemical Structure

CC214-2 Chemical Structure

CAS No. : 1228012-18-7

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Description

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].

IC50 & Target[1][2]

mTORC1

 

mTORC2

 

Cellular Effect
Cell Line Type Value Description References
PC-3 IC50
0.315 μM
Compound: 10b, CC214-2
Inhibition of mTORC2 in human PC3 cells assessed as inhibition of AKTS473 phosphorylation after 1 hr by sandwich immunoassay
Inhibition of mTORC2 in human PC3 cells assessed as inhibition of AKTS473 phosphorylation after 1 hr by sandwich immunoassay
[PMID: 23414803]
PC-3 IC50
0.32 μM
Compound: 26, CC214-2
Inhibition of mTORC2 in human PC3 cells assessed as inhibition of Akt phosphorylation at S473 after 1 hr
Inhibition of mTORC2 in human PC3 cells assessed as inhibition of Akt phosphorylation at S473 after 1 hr
[PMID: 26083478]
PC-3 IC50
0.386 μM
Compound: 10b, CC214-2
Inhibition of mTORC1 in human PC3 cells assessed as inhibition of S6 phosphorylation after 1 hr by sandwich immunoassay
Inhibition of mTORC1 in human PC3 cells assessed as inhibition of S6 phosphorylation after 1 hr by sandwich immunoassay
[PMID: 23414803]
PC-3 IC50
0.39 μM
Compound: 26, CC214-2
Inhibition of mTORC1 in human PC3 cells assessed as inhibition of S6 phosphorylation after 1 hr
Inhibition of mTORC1 in human PC3 cells assessed as inhibition of S6 phosphorylation after 1 hr
[PMID: 26083478]
PC-3 IC50
1.55 μM
Compound: 10b, CC214-2
Cytotoxicity against human PC3 cells assessed as growth inhibition after 3 days by WST1 assay
Cytotoxicity against human PC3 cells assessed as growth inhibition after 3 days by WST1 assay
[PMID: 23414803]
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. tuberculosis infection[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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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.
Molecular Weight

383.44

Formula

C20H25N5O3

CAS No.
Appearance

Solid

Color

Light yellow to light brown

SMILES

O=C1N=C2NC=C(C3=CC=C(C(C)(C)O)N=C3)N=C2N(CC4CCOCC4)C1

Shipping

Room temperature in continental US; may vary elsewhere.

Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
Purity & Documentation

Purity: 98.41%

References
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    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

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CC214-2
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