Torin 2

ArtNr	S2817-10000
Hersteller	Selleckchem
CAS-Nr.	1223001-51-1
Menge	10 g
Kategorie	Oncology Neuroscience Aging & Neurological Disorders Inhibitors & Compound Libraries Small Molecules By Organ Lung Cancer Bladder Cancer Colorectal Cancer Breast Cancer Testicular & Prostate Cancer
Typ	Inhibitors
Specific against	other
ECLASS 10.1	32160490
ECLASS 11.0	32160490
UNSPSC	12000000
Alias	1223001-51-1'
Similar products	Torin
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Administration	Intravenous or oral
Animal Models	male Swiss albino mice
Cell lines	MZ-CRC-1 and TT cells
Chemical Name	Benzo[h]-1, 6-naphthyridin-2(1H)-one, 9-(6-amino-3-pyridinyl)-1-[3-(trifluoromethyl)phenyl]-
Concentrations	50 nM
Description	Torin2 is a highly potent and selective mTOR inhibitor with IC50 of 0.25 nM.
Dosages	25 mg/kg
Formulation	first dissolve at 25 mg/mL in 100% N-methyl-2-pyrrolidone and then dilute 1:4 with sterile 50% PEG400 prior to injection
IC50	0.25 nM [1], 0.25 nM [1], 0.25 nM [1], 0.25 nM [1], 0.25 nM [1], 0.25 nM [1]
In vitro	Torin2 has the same binding mode as PI3Kgamma, 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. [1] Torin2 inhibits mTORC1, thus activates TFEB by promoting its nuclear translocation with EC50 of 1.666 mM. [2] 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. [3]
In vivo	Torin2 exhibits >95% pharmacodynamic response and half-time of 11.7 min in the mouse liver microsome stability study. Torin2 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. [1] Torin2(20mg/kg) ablates MYCN tumors with reduction in MYCN protein levels and induction of apoptosis in Th-MYCN mice. [4]
Incubation Time	3 days or 5 days
Kinase Assay	mTOR and PI3K Cellular Assays, Cellular IC50 values for mTOR are determined using p53 / MEFs. Cells are treated with vehicle or increasing concentrations of Torin2 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.
Method	For viability, MZ-CRC-1 and TT cells are seeded in quadruplicate in 96-well plates (1.0x104 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 uL of CellTiter96 AQueous One solution in 100 uL of culture media and absorbance is measured at 490 nm.
Molecular Weight (MW)	432, 4
Picture ChemicalStructure Description	Torin 2 Chemical Structure
Solubility (25C)	DMSO <1 mg/mL, Water <1 mg/mL, Ethanol <1 mg/mL
Storage	2 years -20CPowder, 2 weeks4Cin DMSO, 2 months-80Cin DMSO

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