| CAS NO: | 1223001-51-1 |
| 规格: | ≥98% |
| 包装 | 价格(元) |
| 5mg | 电议 |
| 25mg | 电议 |
| 50mg | 电议 |
| 100mg | 电议 |
| 250mg | 电议 |
| 500mg | 电议 |
Molecular Weight (MW) | 432.4 |
Formula | C24H15F3N4O |
CAS No. | 1223001-51-1 |
Storage | -20℃ for 3 years in powder form |
-80℃ for 2 years in solvent | |
Solubility (In vitro) | DMSO: 20 mg/mL (46.3 mM) |
Water: <1 mg/mL | |
Ethanol: <1 mg/mL | |
Solubility (In vivo) | 30% PEG400+0.5% Tween80+5% propylene glycol: 30mg/mL |
Synonyms | Torin-2; Torin 2; Torin2 Chemical Name: 9-(6-amino-3-pyridinyl)-1-[3-(trifluoromethyl)phenyl]-benzo[h]-1,6-naphthyridin-2(1H)-one InChi Key: GUXXEUUYCAYESJ-UHFFFAOYSA-N InChi Code: InChI=1S/C24H15F3N4O/c25-24(26,27)17-2-1-3-18(11-17)31-22(32)9-6-16-13-29-20-7-4-14(10-19(20)23(16)31)15-5-8-21(28)30-12-15/h1-13H,(H2,28,30) SMILES Code: O=C1N(C2=CC=CC(C(F)(F)F)=C2)C3=C(C=NC4=CC=C(C5=CC=C(N)N=C5)C=C43)C=C1 |
| In Vitro | Kinase Assay: Cellular IC50 values for mTOR are determined using p53–/– MEFs. Cells are treated with vehicle or increasing concentrations of Torin 2 for 1 h and then lyse. Phosphorylation of S6K1 Thr-389 is monitored by immunoblotting using a phospho-specific antibody. Meanwhile, cellular IC50 values for PI3Ka are determined based on phosphorylation of Akt Thr-308 in p53–/–/mLST8–/– MEFs or human PC3 cells expressing the S473D mutant of Akt1. Cell Assay: For viability, MZ-CRC-1 and TT cells are seeded in quadruplicate in 96-well plates (1.0×104 cells per well) in culture media with 2.5% and 4% FBS, respectively. After 24 hours, cells are treated with Torin 2. At the indicated time point, cells are incubated for 3 hours with 10 μL of CellTiter96 AQueous One solution in 100 μL of culture media and absorbance is measured at 490 nm. Torin 2 has the same binding mode as PI3Kγ, V882 serves as a hinge binding point and in the inner hydrophobic pocket Y867, D841 and D964 provide three more hydrogen bonds with aminopyridine side chain analogous to Y2225, D2195 and D2357 of mTOR. Torin 2 inhibits mTORC1, thus activates TFEB by promoting its nuclear translocation with EC50 of 1.666 mM. Torin 2(< 50 nM) causes a significant reduction in viability of both MZ-CRC-1 and TT cells. Torin 2 (100 nM) exerts a significant reduction of migration of both MZ-CRC-1 and TT cells. |
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| In Vivo | Torin 2 exhibits>95% pharmacodynamic response and half-time of 11.7 min in the mouse liver microsome stability study. Torin 2 exhibits the best bioavailability (51%), short half-life (0.72 hours) and low clearance(19.6 mL/min/kg) in male Swiss albino mice following intravenous and oral administration. Torin 2(20mg/kg) ablates MYCN tumors with reduction in MYCN protein levels and induction of apoptosis in Th-MYCN mice. |
| Animal model | Swiss albino mice |
| Formulation & Dosage | Dissolved in 25 mg/mL in 100% N-methyl-2-pyrrolidone and then dilute 1:4 with sterile 50% PEG400 ; 25 mg/kg; i.v. or oral gavage |
| References | J Med Chem. 2011 Mar 10;54(5):1473-80; EMBO J. 2012 Mar 7;31(5):1095-108; Clin Cancer Res. 2012 Jul 1;18(13):3532-40. |
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