KU-0063794(KU 0063794)
KU-0063794
CAS: 938440-64-3
Molecular Formula: C25H31N5O4
KU-0063794(KU 0063794) - Names and Identifiers
KU-0063794(KU 0063794) - Physico-chemical Properties
| Molecular Formula | C25H31N5O4 |
| Molar Mass | 465.54 |
| Density | 1.248 |
| Boling Point | 694.3±65.0 °C(Predicted) |
| Solubility | DMSO: >2mg/mL (warmed) |
| Appearance | powder |
| Color | white to beige |
| pKa | 14.20±0.10(Predicted) |
| Storage Condition | 2-8°C |
| MDL | MFCD11977741 |
| Use | KU 0063794 |
| In vitro study | Compared to the mTOR inhibitor PP242, KU-0063794 was highly specific for mTOR and had no activity on PI3Ks or the other 76 kinases. 30 nM KU-0063794 acts on HEK-293 cells and rapidly cleaves S6K1 activity by inhibiting phosphorylation of the hydrophobic group (Thr389) and subsequent phosphorylation of the T-ring residue (Thr229). 300 nM KU-0063794 inhibited ~ 90% S6K1 activity in IGF1-stimulated serum-starved HEK-293 cells. When KU-0063794 was 100-300 nM, the phosphorylation of S6K1 and S6 proteins induced by amino acids was also completely inhibited. Similar to S6K1, KU-0063794 inhibited phosphorylation of mTORC1 at the Ser2448 site and also inhibited phosphorylation of mTORC2 at the Ser22481 site, in a dose-and time-dependent manner. KU-0063794 inhibition of Akt activity in the presence of serum, or IGF1 stimulation, or phosphorylation of Akt at Ser473 and Thr308 (unexpected) sites, as well as inhibition of Akt substrate PRAS40 at Thr246 sites, GSK3α/GSK3β was phosphorylated at the Ser21/Ser9 site and Foxo-1/3a at the Thr24/Thr32 site in a dose-dependent manner. KU-0063794, but not Rapamycin, inhibits SGK1 activity and phosphorylation at Ser422 site, and also inhibits its physiological substrate NDGR1, which is similar to the degree of inhibition of S6K1 and Akt phosphorylation, however, KU-0063794 did not inhibit phorbol ester-induced ERK or RSK phosphorylation and RSK activation. KU-0063794 was more effective than Rapamycin in inducing full dephosphorylation of 4E-BP1 at Thr37, Thr46 and Ser65 sites. KU-0063794 inhibited the growth of wild-type and mlst8-deficient MEFs cells and also induced the cell cycle to stop at the G1 phase, which was more pronounced than the Rapamycin effect. compared to the mTOR inhibitor PP242, KU-0063794 was highly specific for mTOR but had no activity for PI3Ks or the other 76 kinases. 30 nM KU-0063794 acts on HEK-293 cells by inhibiting the hydrophobic group (Thr |
| In vivo study | Ku0063794 inhibits tumor growth and mTOR signaling in preclinical models of renal epithelial renal cell carcinoma. However, in animal studies, Ku0063794 was not as effective as temsirolimus, probably because temsirolimus has an important role in the tumor microenvironment and can reduce angiogenesis in xenograft tumors, ku0063794 had no such effect. Tumor tissues treated with Temsirolimus expressed less VEGF and PDGF than those treated with ku0063794. |
KU-0063794(KU 0063794) - Risk and Safety
| Hazard Symbols | T - Toxic |
| Risk Codes | 25 - Toxic if swallowed |
| Safety Description | 45 - In case of accident or if you feel unwell, seek medical advice immediately (show the label whenever possible.) |
| WGK Germany | 3 |
KU-0063794(KU 0063794) - Preparation solution concentration reference
| 1mg | 5mg | 10mg | |
|---|---|---|---|
| 1 mM | 2.148 ml | 10.74 ml | 21.48 ml |
| 5 mM | 0.43 ml | 2.148 ml | 4.296 ml |
| 10 mM | 0.215 ml | 1.074 ml | 2.148 ml |
| 5 mM | 0.043 ml | 0.215 ml | 0.43 ml |
Last Update：2024-01-02 23:10:35
KU-0063794(KU 0063794) - Reference Information
| biological activity | KU-0063794 is an effective, highly specific, dual mTOR inhibitor acting on mTORC1 and mTORC2, with an IC50 of about ~ 10 nM; No effect on PI3Ks. KU-0063794 is an effective and highly specific dual mTOR inhibitor acting on mTORC1 and mTORC2. IC50 is about ~ 10 nM in cell-free test. It has no effect on PI3Ks. |
| In vitro study | Compared with the mTOR inhibitor PP242, the KU-0063794 has high specificity on mTOR, but has no activity on PI3Ks or other 76 kinases. 30 nM KU-0063794 acts on HEK-293 cells to rapidly excise S6K1 activity by inhibiting phosphorylation of hydrophobic group (Thr389) and subsequent phosphorylation of T-ring residue (Thr229). 300 nM KU-0063794 acts on IGF1-stimulated serum starved HEK-293 cells and inhibits ~ 90% S6K1 activity. Amino acid-induced phosphorylation of S6K1 and S6 proteins was also completely inhibited at a KU-0063794 of 100-300 nM. Similar to S6K1, KU-0063794 inhibits phosphorylation of mTORC1 at Ser2448 sites and phosphorylation of mTORC2 at Ser22481 sites in a dose-and time-dependent manner. In the presence of serum or stimulated by IGF1, KU-0063794 inhibits Akt activity, or Akt phosphorylation at Ser473 and Thr308 (unexpected) sites, and also inhibits Akt substrate PRAS40 at Thr246 site, GSK3α/GSK3β at Ser21/Ser9 site and Foxo-1/3a at Thr24/Thr32 site. The above effects are dose-dependent. KU-0063794, rather than Rapamycin, inhibits SGK1 activity and phosphorylation at Ser422 site, and also inhibits its physiological substrate NDGR1, which is similar to the degree of phosphorylation of S6K1 and Akt. This effect is dose-dependent, but KU-0063794 does not inhibit the phosphorylation of ERK or RSK induced by phorbol ester and RSK activation. Compared with Rapamycin, KU-0063794 more effectively induced complete dephosphorylation of 4E-BP1 at Thr37, Thr46 and Ser65 sites. KU-0063794 inhibit the growth of wild-type and mLST8-deficient MEFs cells and induce the cell cycle to stop at G1 phase, which is more effective than Rapamycin. Compared with the mTOR inhibitor PP242, KU-0063794 has high specificity on mTOR, but has no activity on PI3Ks or other 76 kinases. 30 nM KU-0063794 acts on HEK-293 cells by inhibiting hydrophobic groups (Thr |
| target | TargetValue mTORC1 (cell-free say) ~ 10 nM mTORC2 (cell-free say) ~ 10 nM |
| Target | Value |
| mTORC1 (Cell-free assay) | ~10 nM |
| mTORC2 (Cell-free assay) | ~10 nM |
| in vivo study | Ku0063794 inhibit tumor growth and mTOR signal in preclinical models of renal epithelial renal cell carcinoma. However, in animal studies, Ku0063794 is not temsirolimus effective. The possible reason is that temsirolimus plays an important role in the microenvironment of tumors and can reduce angiogenesis in xenograft tumors, but Ku0063794 does not have this effect. Temsirolimus-treated tumor tissues expressed VEGF and PDGF less than Ku0063794-treated tumor tissues. |
Last Update：2024-04-09 21:54:55
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CAS: 938440-64-3
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Product Name: KU-0063794 Visit Supplier Webpage Request for quotation
CAS: 938440-64-3
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
CAS: 938440-64-3
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
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