Torin 2

Torin 2 is a potent and selective mTOR inhibitor with IC50 of 0.25 nM in p53−/− MEFs cell line; 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,in PC3 cell lines respectively. Torin 2 decreases cell viability and induces autophagy and apoptosis.

CAS No. 1223001-51-1

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 28500	国内在庫あり
5mg	JPY 22000	国内在庫あり
10mg	JPY 34000	国内在庫あり
25mg	JPY 55500	国内在庫あり
1g	JPY 448500	国内在庫なし(納期7~10日)

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製品安全説明書

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Torin 2関連製品

関連ターゲット	mTORC1 mTORC2	もっと見る
関連製品	Rapamycin (Sirolimus) Everolimus AZD8055 Torin 1 Ridaforolimus (Deforolimus, MK-8669) Sapanisertib (MLN0128) Temsirolimus Torkinib (PP242) Vistusertib (AZD2014) MHY1485 KU-0063794 OSI-027 WYE-354 WYE-125132 (WYE-132) 3BDO Palomid 529 (P529) Zotarolimus (ABT-578) Salidroside GDC-0349 WAY-600 Onatasertib (CC 223) XL388 WYE-687	もっと見る
関連化合物ライブラリー	Kinase Inhibitor Library PI3K/Akt Inhibitor Library Apoptosis Compound Library Cell Cycle compound library NF-κB Signaling Compound Library	もっと見る

シグナル伝達経路

mTORシグナル伝達経路

mTOR阻害剤の選択性比較

Cell Data

Cell Lines	Assay Type	Incubation Time	活性情報	PMID
HCT116	Function assay	1 hr	Inhibition of mTORC1 in human HCT116 cells assessed as reduction in T389 phosphorylation on RPS6KB1 after 1 hr by Western blot analysis, EC50=0.00025μM	29211480
HEK293T	Function assay	20 mins	Inhibition of N-terminally FLAG-tagged mTORC1 (unknown origin) expressed in HEK293T cells using S6K1 or Akt1 as substrate after 20 mins by immunoblotting assay, IC50<0.01μM	29211480
HeLa	Function assay	20 mins	Inhibition of N-terminally FLAG-tagged mTORC2 (unknown origin) expressed in human HeLa cells using S6K1 or Akt1 as substrate after 20 mins by immunoblotting assay, IC50<0.01μM	29211480
RD	Antiviral assay	4 days	Antiviral activity against Enterovirus A71 infected in human RD cells assessed as reduction in virus-induced cell death incubated for 4 days by CellTiter-Glo luminescence assay, IC50=0.01μM	31082764
HCT116	Function assay	1 hr	Inhibition of ATM in human HCT116 cells assessed as after 1 hr by Western blot analysis, EC50=0.028μM	29211480
HCT116	Function assay	1 hr	Inhibition of ATR in human HCT116 cells assessed as after 1 hr by Western blot analysis, EC50=0.035μM	29211480
RD	Cytotoxicity assay	4 days	Cytotoxicity against human RD cells incubated for 4 days by CellTiter-Glo luminescence assay, CC50=0.04μM	31082764
HCT116	Function assay	1 hr	Inhibition of DNAPK in human HCT116 cells assessed as after 1 hr by Western blot analysis, EC50=0.118μM	29211480
MOLM13	Antiproliferative assay		Antiproliferative activity against human MOLM13 cells by Cell-Titer Glo assay, IC50<0.001μM	30370766
MOLM14	Antiproliferative assay		Antiproliferative activity against human MOLM14 cells by Cell-Titer Glo assay, IC50<0.001μM	30370766
MV4-11	Antiproliferative assay		Antiproliferative activity against human MV4-11 cells by Cell-Titer Glo assay, IC50<0.001μM	30370766
PC3	Function assay		Inhibition of PI3Kalpha in human PC3 cells expressing Akt1 S473D mutant assessed as phosphorylation of Akt Thr308 by immunoblotting, EC50=0.2μM	21322566
TC32	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells	29435139
DAOY	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells	29435139
SJ-GBM2	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells	29435139
A673	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells	29435139
SK-N-MC	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells	29435139
BT-37	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells	29435139
NB-EBc1	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells	29435139
U-2 OS	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS cells	29435139
Saos-2	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells	29435139
NB1643	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells	29435139
LAN-5	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells	29435139
BT-12	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-12 cells	29435139
Rh18	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells	29435139
OHS-50	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells	29435139
RD	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells	29435139
MG 63 (6-TG R)	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for MG 63 (6-TG R) cells	29435139
Rh30	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh30 cells	29435139
Rh41	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells	29435139
NB1643	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB1643 cells	29435139
A673	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 cells)	29435139
SK-N-MC	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells	29435139
LAN-5	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for LAN-5 cells	29435139
DAOY	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY cells	29435139
NB-EBc1	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB-EBc1 cells	29435139
SJ-GBM2	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SJ-GBM2 cells	29435139
BT-37	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for BT-37 cells	29435139
TC32	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells	29435139
MG 63 (6-TG R)	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells	29435139
U-2 OS	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells	29435139
Rh41	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells	29435139
RD	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for RD cells	29435139
Rh18	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh18 cells	29435139
Rh30	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh30 cells	29435139
Saos-2	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Saos-2 cells	29435139
OHS-50	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for OHS-50 cells	29435139
SK-N-SH	qHTS assay		qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells	29435139
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生物活性

製品説明

Torin 2 is a potent and selective mTOR inhibitor with IC50 of 0.25 nM in p53−/− MEFs cell line; 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,in PC3 cell lines respectively. Torin 2 decreases cell viability and induces autophagy and apoptosis.

Targets

mTOR ^[1] (p53−/− MEFs)	ATM ^[5] (PC3 cells)	ATR ^[5] (PC3 cells)	DNA-PK ^[5] (PC3 cells)
0.25 nM	28 nM(EC50)	35 nM(EC50)	118 nM(EC50)

In Vitro
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. ^[1] Torin 2 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]
Kinase Assay	mTOR and PI3K Cellular Assays
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.
細胞実験	細胞株	MZ-CRC-1 and TT cells
	濃度	50 nM
	反応時間	3 days or 5 days
	実験の流れ	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.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	p-S6K / S6K / p-AKT / AKT / IRS1 / p-4EBP1 / 4EBP1 / p-GSK3 p-Chk1 / Chk1 / p-Chk2 / Chk2 / p-DNA-PK		23436801
	Immunofluorescence	LC3B		23436801
	Growth inhibition assay	Cell viability		24434750

In Vivo
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. ^[1] Torin 2(20mg/kg) ablates MYCN tumors with reduction in MYCN protein levels and induction of apoptosis in Th-MYCN mice. ^[4]
動物実験	動物モデル	male Swiss albino mice
	投与量	20 mg/kg
	投与経路	Intravenous or oral

参考
[1] Liu Q, et al. J Med Chem, 2011, 54(5), 1473-1480. [2] Settembre C, et al. EMBO J, 2012, 31(5), 1095-1108. [3] Tamburrino A, et al. Clin Cancer Res, 2012, 18(13), 3532-3540. [4] Berry T, et al. Cancer Cell, 2012, 22(1), 117-130. [5] Liu Q, et al. Cancer Res, 2013, 73(8), 2574-2586. + 展開

参考

+ 展開

化学情報

分子量	432.4	化学式	C₂₄H₁₅F₃N₄O
CAS No.	1223001-51-1	SDF	Download Torin 2 SDFをダウンロードする
Smiles	C1=CC(=CC(=C1)N2C(=O)C=CC3=CN=C4C=CC(=CC4=C32)C5=CN=C(C=C5)N)C(F)(F)F
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1年-80°Cin solvent
保管	3年-20°C粉	溶液の保管冷凍と解凍の繰り返しを避けるため小分けにしてください	1个月-20°Cin solvent

In vitro
Batch:

DMSO : 41 mg/mL ( (94.81 mM)；吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Water : Insoluble

Ethanol : Insoluble

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量	濃度	体積	分子量
=	×	×

希釈計算器分子量計算器

投与溶液組成計算機(クリア溶液)

ステップ１：実験データを入力してください。（実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します）

投与量 mg/kg 動物平均体重 g 投与体積（動物毎）μL 動物数匹

ステップ２：投与溶媒の組成を入力してください。（ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください）

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

計算結果：

投与溶媒濃度： mg/ml;

DMSOストック溶液調製方法： mg 試薬を μL DMSOに溶解する（濃度 mg/mL, 注：濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法：Take μL DMSOストック溶液に μL PEG300，を加え、完全溶解後μL Tween 80，を加えて完全溶解させた後 μL ddH₂O，を加え完全に溶解させます。

投与溶媒調製方法：μL DMSOストック溶液に μL Corn oil，を加え、完全溶解。

注意：１.ストック溶液に沈殿、混濁などがないことをご確認ください；
２.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

C1=C0/X	C1:	LOG(C1):
C2=C1/X	C2:	LOG(C2):
C3=C2/X	C3:	LOG(C3):
C4=C3/X	C4:	LOG(C4):
C5=C4/X	C5:	LOG(C5):
C6=C5/X	C6:	LOG(C6):
C7=C6/X	C7:	LOG(C7):
C8=C7/X	C8:	LOG(C8):