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Torin 2

Cat No.
CEI-0857
Description
Torin 2 is a potent and selective mTOR inhibitor with IC50 of 0.25 nM; 800-fold greater selectivity for mTOR than PI3K and improved pharmacokinetic properties. Inhibition of ATM/ATR/DNA-PK with EC50 of 28 nM/35 nM/118 nM, respectively.
CAS No.
1223001-51-1
Molecular Weight
432.4
Storage
2 years -20 centigrade Powder; 2 weeks 4 centigrade in DMSO; 6 months -80 centigrade in DMSO.
Targets
mTOR, ATM, ATR, DNA-PK
IC50
0.25 nM; 28 nM; 35 nM; 118 nM
Molecular Formula
C24H15F3N4O
Chemical Name
Benzo[h]-1,6-naphthyridin-2(1H)-one, 9-(6-amino-3-pyridinyl)-1-[3-(trifluoromethyl)phenyl]-
Solubility
DMSO 20 mg/mL; Water <1 mg/mL; Ethanol <1 mg/mL
In vitro
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.
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