Torkinib (PP242)

Torkinib (PP242) is a selective mTOR inhibitor with IC50 of 8 nM in cell-free assays; targets both mTOR complexes with >10- and 100-fold selectivity for mTOR than PI3Kδ or PI3Kα/β/γ, respectively. Torkinib (PP242) induces mitophagy and apoptosis.

CAS No. 1092351-67-1

サイズ	価格(税別)	在庫状況
10mM (1mL in DMSO)	JPY 29500	国内在庫あり
5mg	JPY 22000	国内在庫あり
50mg	JPY 55500	国内在庫あり
1g	JPY 430500	国内在庫なし(納期7~10日)

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Torkinib (PP242)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 Vistusertib (AZD2014) MHY1485 KU-0063794 Torin 2 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	Concentration	Incubation Time	活性情報	PMID
HT-p21	Function Assay	50-1250 nM	24 h	inhibits phosphorylation of S6 kinase (target of mTORC1) and its downstream target phospho-S6	26177051
U87vIII	Function Assay	0.04-2.5 μM	24 h	inhibits mTORC1 and mTORC2 activities	26134617
U87vIII	Function Assay	2.5/5 μM	12 h	inhibits gap closing in a dose-dependent manner	26134617
3T3-L1	Function Assay	15 μM	4 h	suppresses expression of the Egr1 protein	25814662
Rh30	Function Assay	1 μM	2 h	inhibits both mTORC1-mediated phosphorylation of S6K1 and mTORC2-mediated phosphorylation of Akt	25762619
HT29	Function Assay	1 μM	2 h	inhibits both mTORC1-mediated phosphorylation of S6K1 and mTORC2-mediated phosphorylation of Akt	25762619
Rh30	Function Assay	1 μM	2 h	suppresses the basal or IGF-1-stimulated cell adhesion	25762619
HT29	Function Assay	1 μM	2 h	suppresses the basal or IGF-1-stimulated cell adhesion	25762619
U87	Growth Inhibition Assay	25 nM	24 h	increases DUSP10 knocked-down induced cell inhibition	25568665
AGS	Cell Viability Assay	0-1000 nM	24/48 h	decreases cell viability in time and dose dependent manner	25035961
MKN45	Cell Viability Assay	0-1000 nM	24/48 h	decreases cell viability in time and dose dependent manner	25035961
MKN28	Cell Viability Assay	0-1000 nM	24/48 h	decreases cell viability in time and dose dependent manner	25035961
KATO3	Cell Viability Assay	0-1000 nM	24/48 h	decreases cell viability in time and dose dependent manner	25035961
SGC7901	Cell Viability Assay	0-1000 nM	24/48 h	decreases cell viability in time and dose dependent manner	25035961
N87	Cell Viability Assay	0-1000 nM	24/48 h	decreases cell viability in time and dose dependent manner	25035961
HMEC	Cell Viability Assay	0-1000 nM	24/48 h	decreases cell viability in time and dose dependent manner	25035961
HUVEC	Cell Viability Assay	0-1000 nM	24/48 h	decreases cell viability in time and dose dependent manner	25035961
MG63	Function Assay	50-1000 nM	0.5 h	dose dependently (50–1000 nM) inhibits phosphorylation of Akt	24840134
U2OS	Function Assay	50-1000 nM	0.5 h	dose dependently (50–1000 nM) inhibits phosphorylation of Akt	24840134
Saos-2	Function Assay	50-1000 nM	0.5 h	dose dependently (50–1000 nM) inhibits phosphorylation of Akt	24840134
Saos-2	Function Assay	100 nM	0.5 h	prevents osteosarcoma cell migration	24840134
MG63	Apoptosis Assay	100 nM	36 h	promotes apoptosis	24840134
U2OS	Apoptosis Assay	100 nM	36 h	promotes apoptosis	24840134
Saos-2	Apoptosis Assay	100 nM	36 h	promotes apoptosis	24840134
DLD-1	Cell Viability Assay	0-1000 nM	24 h	inhibits the growth in a dose-dependent manner	23991179
Caco2	Cell Viability Assay	0-1000 nM	24 h	inhibits the growth in a dose-dependent manner	23991179
HT29	Cell Viability Assay	0-1000 nM	24 h	inhibits the growth in a dose-dependent manner	23991179
H116	Cell Viability Assay	0-1000 nM	24 h	inhibits the growth in a dose-dependent manner	23991179
Hct-8	Cell Viability Assay	0-1000 nM	24 h	inhibits the growth in a dose-dependent manner	23991179
Colo320	Cell Viability Assay	0-1000 nM	24 h	inhibits the growth in a dose-dependent manner	23991179
Sw948	Cell Viability Assay	0-1000 nM	24 h	inhibits the growth in a dose-dependent manner	23991179
Colo205	Cell Viability Assay	0-1000 nM	24 h	inhibits the growth in a dose-dependent manner	23991179
Colo320	Function Assay	1 μM	0-24 h	abolishes the S6S235/236 but partially reduces the 4E-BP1T36/45	23991179
HT29	Function Assay	1 μM	0-24 h	abolishes the S6S235/236 but partially reduces the 4E-BP1T36/45	23991179
Sw948	Function Assay	1 μM	0-24 h	abolishes the S6S235/236 but partially reduces the 4E-BP1T36/45	23991179
DLD-1	Function Assay	1 μM	0-24 h	abolishes the S6S235/236 but partially reduces the 4E-BP1T36/45	23991179
786-O	Function Assay	0.1/0.5 μM	24 h	increases E-cadherin mRNA levels dose dependently	23147251
786-O	Function Assay	0-0.5 μM	24 h	results in a dose dependent increase in E-cadherin protein expression	23147251
OCI-AML3	Apoptosis Assay	2.5 μM	72 h	induces apoptosis	22826565
Jurkat	Function Assay	100/200/400 nM	18 h	inhibits mTORC1-dependent S6 S235/236 phosphorylation	22566604
p210 BCR-Abl	Function Assay	100/200/400 nM	18 h	inhibits mTORC1-dependent S6 S235/236 phosphorylation	22566604
Jurkat	Growth Inhibition Assay	400nM	24/48 h	synergize with 17-AAG to suppress cell proliferation	22566604
p210 BCR-Abl	Growth Inhibition Assay	400nM	24/48 h	synergize with 17-AAG to suppress cell proliferation	22566604
8226	Function Assay	100-1000 nM	30 min	activates ERK	22556409
MM1.S	Function Assay	100-1000 nM	30 min	activates ERK	22556409
8226	Function Assay	0.5 μM	30 min	induces activation of RAF and phosphorylation of MEK	22556409
MM1.S	Function Assay	0.5 μM	30 min	induces activation of RAF and phosphorylation of MEK	22556409
MCF-7	Function Assay	50/200/500 nM	30 min	dose-dependently (50–500 nM) suppresses phosphorylation of Akt	22476852
T47D	Function Assay	50/200/500 nM	30 min	dose-dependently (50–500 nM) suppresses phosphorylation of Akt	22476852
MDA-MB-231	Function Assay	50/200/500 nM	30 min	dose-dependently (50–500 nM) suppresses phosphorylation of Akt	22476852
Bcap-37	Function Assay	50/200/500 nM	30 min	dose-dependently (50–500 nM) suppresses phosphorylation of Akt	22476852
MCF-7	Apoptosis Assay	200 nM	36 h	induces apoptosis	22476852
MDA-MB-231	Apoptosis Assay	200 nM	36 h	induces apoptosis	22476852
Bcap-37	Apoptosis Assay	200 nM	36 h	induces apoptosis	22476852
LS174T	Function Assay	10/100/1000 nM	6 h	inhibits mTORC1 activity by the dephosphorylation of S6 ribosomal protein	22401294
DLD-1	Function Assay	10/100/1000 nM	6 h	inhibits mTORC1 activity by the dephosphorylation of S6 ribosomal protein	22401294
SW480	Function Assay	10/100/1000 nM	6 h	inhibits mTORC1 activity by the dephosphorylation of S6 ribosomal protein	22401294
NIH 3T3	Function Assay	2 μM	18 h	inhibits mTORC2 phosphorylation of Akt on Ser473 and mTORC1 phosphorylation of 4E-BP1 on Thr37/46	21876130
HCT15	Function Assay	0.5/2 μM	4 h	prevents S6K1 phosphorylation of ribosomal protein S6 at Ser240/244 and mTORC2 phosphorylation of Akt at Ser473	21876130
SW620	Function Assay	0.5/2 μM	4 h	blocks all three mTOR outputs	21876130
PC12	Function Assay	40 nM		induces lysosomal biogenesis and alleviated α-SYN accumulation	26001614
DND-1	Growth Inhibition Assay	0.25/0.5/1 μM		inhibits cell growth dose dependently	23482748
TMD8	Growth Inhibition Assay	0.25/0.5/1 μM		inhibits cell growth dose dependently	23482748
Jurkat	Growth Inhibition Assay	0.25/0.5/1 μM		inhibits cell growth dose dependently	23482748
KOPT-K1	Growth Inhibition Assay	0.25/0.5/1 μM		inhibits cell growth dose dependently	23482748
TMD7	Growth Inhibition Assay	0.25/0.5/1 μM		inhibits cell growth dose dependently	23482748
THP-1	Growth Inhibition Assay	0.25/0.5/1 μM		inhibits cell growth dose dependently	23482748
HT1376	Growth Inhibition Assay			IC50=1.88 ± 1.1 μM	24054871
T24	Growth Inhibition Assay			IC50=1.37 ± 0.4 μM	24054871
UM-UC-3	Growth Inhibition Assay			IC50=0.63 ±0.1 μM	24054871
SW620	Growth Inhibition Assay			IC50=7.8 μM	23542178
SW480	Growth Inhibition Assay			IC50=4.6 μM	23542178
SK-CO-1	Growth Inhibition Assay			IC50=4 μM	23542178
LS-513	Growth Inhibition Assay			IC50=3.9 μM	23542178
SW1116	Growth Inhibition Assay			IC50=0.84 μM	23542178
LS-174T	Growth Inhibition Assay			IC50=0.84 μM	23542178
HCT 116	Growth Inhibition Assay			IC50=0.41 μM	23542178
HCT 15	Growth Inhibition Assay			IC50=0.3 μM	23542178
COLO 205	Growth Inhibition Assay			IC50=0.24 μM	23542178
HT-29	Growth Inhibition Assay			IC50=0.23 μM	23542178
COLO 201	Growth Inhibition Assay			IC50=0.23 μM	23542178
Caco-2	Growth Inhibition Assay			IC50=0.22 μM	23542178
SW48	Growth Inhibition Assay			IC50=0.09 μM	23542178
SW-48	Growth Inhibition Assay			IC50=0.1 μM	22270257
HCT-15	Growth Inhibition Assay			IC50=0.3 μM	22270257
HCT 116	Growth Inhibition Assay			IC50=0.6 μM	22270257
SW620-R	Growth Inhibition Assay			IC50=1.3 μM	22270257
SK-CO-1	Growth Inhibition Assay			IC50=2.1 μM	22270257
SW620	Growth Inhibition Assay			IC50=11 μM	22270257
BaF3	Growth Inhibition Assay			GI50=1.449 μM	22223645
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生物活性

製品説明

Torkinib (PP242) is a selective mTOR inhibitor with IC50 of 8 nM in cell-free assays; targets both mTOR complexes with >10- and 100-fold selectivity for mTOR than PI3Kδ or PI3Kα/β/γ, respectively. Torkinib (PP242) induces mitophagy and apoptosis.

特性

One of the first selective inhibitors that targets ATP domain of mTOR.

Targets

mTOR ^[1] (Cell-free assay)	p110δ ^[1] (Cell-free assay)	DNA-PK ^[1] (Cell-free assay)	PDGFR ^[1] (Cell-free assay)
8 nM	0.10 μM	0.41 μM	0.41 μM

In Vitro
In vitro	PP242 exhibits potent selectivity for mTOR over other PI3K family kinases such as p110α, p110β, p110γ, p110δ, and DNA-PK with IC50 of 1.96 μM, 2.2 μM, 1.27 μM, 0.102 μM, and 0.408 μM, respectively. PP242 displays some inhibitory activity against Ret, PKCα, PKCβ, and JAK2, while exhibits remarkable selectivity against 215 other protein kinases. Unlike rapamycin, PP242 inhibits both mTORC1 and mTORC2. In BT549 cells, PP242 treatment (0.04-10 μM) inhibits the phosphorylation of Akt, the mTOR substrate p70S6K, and its downstream target S6 in a dose-dependent manner. ^[1] PP242 potently inhibits PKCα with IC50 of 49 nM. Low concentrations of PP242 inhibit the phosphorylation of Akt S473 and higher concentrations partially inhibit Akt T308-P in addition to S473-P. As PP242 is a more effective mTORC1 inhibitor than rapamycin, PP242 inhibits the proliferation of primary MEFs, and the phosphorylation of 4EBP1 at T36/45 and S65, more potently than rapamycin. PP242 but not rapamycin potently inhibits cap-dependent translation, by causing a higher level of binding between 4EBP1 and eIF4E than rapamycin. ^[2] PP242 potently inhibits the proliferation of p190-transformed murine BM, SUP-B15, and K562 cells with GI50 of 12 nM, 90 nM, and 85 nM, respectively. PP242 also inhibits the growth of solid tumor cell lines such as SKOV3, PC3, 786-O, and U87 with GI50 of 0.49 μM, 0.19 μM, 2.13 μM, and 1.57 μM, respectively. ^[3] PP242 is also more effective than rapamycin in achieving cytoreduction and apoptosis in multiple myeloma (MM) cells. ^[4]
Kinase Assay	In vitro mTOR (FRAP1) kinase assay
Kinase Assay	Recombinant mTOR is incubated with PP242 at 2-fold dilutions over a concentration range of 50-0.001 μM in an assay containing 50 mM HEPES, pH 7.5, 1 mM EGTA, 10 mM MgCl₂, 0.01% Tween, 10 μM ATP (2.5 μCi of γ-³²P-ATP), and 3 μg/mL BSA. Rat recombinant PHAS-1/4EBP1 (2 mg/mL) is used as a substrate. Reactions are terminated by spotting onto nitrocellulose, which is washed with 1 M NaCl/1% phosphoric acid (approximately 6 times, 5-10 minutes each). Sheets are dried and the transferred radioactivity quantitated by phosphorimaging. IC50 value is calculated by fitting the data to a sigmoidal dose-response curve using the Prism software package.
細胞実験	細胞株	MEFs
	濃度	Dissolved in DMSO, final concentrations ~10 μM
	反応時間	72 hours
	実験の流れ	Cells are treated with increasing concentrations of PP242 for 72 hours in 96-well plates. After 72 hours of treatment, 10 μL of 440 μM resazurin sodium salt is added to each well, and after 18 hours, the florescence intensity in each well is measured using a top-reading florescent plate reader with excitation at 530 nm and emission at 590 nm.
実験結果図	Methods	Biomarkers	結果図	PMID
	Western blot	p-mTOR / mTOR / p-AKT / AKT / p-S6 / S6 / p-4E-BP1 / 4E-BP-1		23991179
	Growth inhibition assay	Cell viability		23991179

In Vivo
In Vivo	Administration of PP242 is able to completely inhibit the phosphorylation of Akt at S473 and T308 in fat and liver of mice. PP242 only partially inhibits the phosphorylation of Akt in skeletal muscle and is more effective at inhibiting the phosphorylation of T308 than S473, despite able to fully inhibit the phosphorylation of 4EBP1 and S6. ^[2] Oral administration PP242 potently delays the leukemia onset in the mice model, and induces leukemia regression by inhibiting mTORC2 and mTORC1 activation that correlates with loss in cell size. ^[3] PP242 treatment potently inhibits the growth of 8226 cells in mice. ^[4]
動物実験	動物モデル	Syngeneic (Balbc/J) mice with mouse p190-transformed BM cells to initiate leukemia, and female NSG mice injected (i.v.) with SUP-B15ffLuc cells or human Ph+ leukemia
	投与量	~60 mg/kg/day
	投与経路	Oral gavage

参考
[1] Apsel B, et al. Nat Chem Biol, 2008, 4(11), 691-699. [2] Feldman ME, et al. PLoS Biol, 2009, 7(2), 0371-0383. [3] Janes MR, et al. Nat Med, 2010, 16(2), 205-213. [4] Hoang B, et al. Blood, 2010, 116(22), 4560-4568. + 展開

参考

[4] Hoang B, et al. Blood, 2010, 116(22), 4560-4568.

+ 展開

化学情報

分子量	308.34	化学式	C₁₆H₁₆N₆O
CAS No.	1092351-67-1	SDF	Download Torkinib (PP242) SDFをダウンロードする
Smiles	CC(C)N1C2=NC=NC(=C2C(=N1)C3=CC4=C(N3)C=CC(=C4)O)N
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 : 61 mg/mL ( (197.83 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):