product name Torin 2
Description: Torin 2 is a potent and selective mTOR inhibitor with IC50 of 0.25 nM in p53−/− MEFs cell line; it demonstrated 800-fold greater selectivity for mTOR than PI3K and improved pharmacokinetic properties. Torin2 is predicted to engage in hydrogen bonds with V2240 and Y2225 of a homology model of mTOR. It also form two hydrogen bonds between the aniline amino group of it with D2195 and D2357, making it more potent than Torin1. Besides that, Torin2 shows excellent overall selectivity and has strong binding to mTOR, CSNK1E, several PI3Ks, CSF1R and MKNK2.
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.
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
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19395317
| 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. |
|---|---|
| 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. |
Related Posts
product name Torin 2
Description: Torin 2 is a potent and selective mTOR inhibitor with IC50 of 0.25 nM in p53−/− MEFs cell line; it demonstrated 800-fold greater selectivity for mTOR than PI3K and improved pharmacokinetic properties. Torin2 is predicted to engage in hydrogen bonds with V2240 and Y2225 of a homology model of mTOR. It also form two hydrogen bonds between the aniline amino group of it with D2195 and D2357, making it more potent than Torin1. Besides that, Torin2 shows excellent overall selectivity and has strong binding to mTOR, CSNK1E, several PI3Ks, CSF1R and MKNK2.
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.
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
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19395317
| 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. |
|---|---|
| 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. |