Details
| Stereochemistry | ACHIRAL |
| Molecular Formula | C25H31N5O4 |
| Molecular Weight | 465.5447 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 2 / 2 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
COC1=CC=C(C=C1CO)C2=NC3=NC(=NC(N4CCOCC4)=C3C=C2)N5C[C@H](C)O[C@H](C)C5
InChI
InChIKey=RFSMUFRPPYDYRD-CALCHBBNSA-N
InChI=1S/C25H31N5O4/c1-16-13-30(14-17(2)34-16)25-27-23-20(24(28-25)29-8-10-33-11-9-29)5-6-21(26-23)18-4-7-22(32-3)19(12-18)15-31/h4-7,12,16-17,31H,8-11,13-15H2,1-3H3/t16-,17+
DescriptionCurator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/23349989 | https://www.ncbi.nlm.nih.gov/pubmed/23303455 | https://www.ncbi.nlm.nih.gov/pubmed/24244612
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/23349989 | https://www.ncbi.nlm.nih.gov/pubmed/23303455 | https://www.ncbi.nlm.nih.gov/pubmed/24244612
KU-0063794 was originally developed as part of the Kudos Biochemical experimental program, Pfizer in 2009 bought Kudos Biochemicals for its pipeline portfolio; KU has not been clinically developed since then. KU-0063794 is a highly specific inhibitor against mTOR 1 and 2 with IC50 of approximately 3-100 nM for mTOR1 and 2 depending on which cell line is tested. KU-0063794 dis played no activity at PI 3-kinase or 76 other kinases tested, it Inhibits activation and hydrophobic motif phosphorylation of Akt, S6K and SGK, but not RSK, in addition, this compound suppresses cell growth and induces G1 cell cycle arrest in vitro. Ku-0063794 was effective in decreasing the viability and growth of renal cell carcinoma, Caki-1 and 786-O, in vitro by inducing cell cycle arrest and autophagy, but not apoptosis. In addition, experiments in vitro showed that Ku-0063794 possessed therapeutic potential for the treatment of keloid disease and acute lymphoblastic leukemia.
Approval Year
PubMed
| Title | Date | PubMed |
|---|---|---|
| Ku-0063794 is a specific inhibitor of the mammalian target of rapamycin (mTOR). | 2009 Jun 12 |
|
| Discovery of 9-(6-aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one (Torin2) as a potent, selective, and orally available mammalian target of rapamycin (mTOR) inhibitor for treatment of cancer. | 2011 Mar 10 |
|
| The synergistic interaction of MEK and PI3K inhibitors is modulated by mTOR inhibition. | 2012 Apr 10 |
|
| Harnessing the PI3K/Akt/mTOR pathway in T-cell acute lymphoblastic leukemia: eliminating activity by targeting at different levels. | 2012 Aug |
Patents
Sample Use Guides
Xenograft Model: Six-week-old female, Nu/Nu nude mice were used for renal cell carcinoma (RCC) model. Approximately 5×106 786-O cells were injected subcutaneously into the flank, and the tumors were allowed to reach 5 mm in diameter before starting treatment. The mice were randomly divided into three groups and treated once daily (five days a week) by intraperitoneal (IP) injection with DMSO (vehicle control), temsirolimus (0.6 mg/kg), or Ku0063794 (8 mg/kg).
Route of Administration:
Intraperitoneal
HEK-293 cell extracts were subjected to immunoprecipitation (IP) with pre-immune (IgG), anti-Raptor or anti-Rictor antibody. The immunoprecipitates were incubated with dephosphorylated GST–S6K1 or GST–Akt1 in the presence of the 1-1000 nM Ku-0063794 concentrations. Kinases assays were performed for 30 min in the presence of MgATP and then subjected to immunoblot analysis with the indicated antibodies. At 1 μM Ku-0063794, which completely suppressed mTORC1 and mTORC2 activity. Ku-0063794, even at concentrations of 10 μM, did not significantly inhibit seven lipid kinases tested (Class I PI3Kα and PI3Kβ, Class II PI3K-B, Class III VPS34 as well as SPHK-1, SPHK-2 and choline kinase). Concentrations of 100–300 nM Ku-0063794 were required to fully suppress amino-acid-induced phosphorylation of S6K1 and S6 protein
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16736978
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85572
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81HJG228AB
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938440-64-3
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DTXSID50239782
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ACTIVE MOIETY
