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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.

Torkinib (PP242)化学構造

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
JPY 22000 国内在庫あり
JPY 55500 国内在庫あり
JPY 430500 国内在庫なし(納期7~10日)

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Torkinib (PP242)関連製品

シグナル伝達経路

mTOR Signaling Pathways

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 
U87vIII  Function Assay 0.04-2.5 μM 24 h inhibits mTORC1 and mTORC2 activities 
U87vIII  Function Assay 2.5/5 μM 12 h inhibits gap closing in a dose-dependent manner
3T3-L1 Function Assay 15 μM 4 h suppresses expression of the Egr1 protein 
Rh30 Function Assay 1 μM 2 h inhibits both mTORC1-mediated phosphorylation of S6K1 and mTORC2-mediated phosphorylation of Akt
HT29 Function Assay 1 μM 2 h inhibits both mTORC1-mediated phosphorylation of S6K1 and mTORC2-mediated phosphorylation of Akt
Rh30 Function Assay 1 μM 2 h suppresses the basal or IGF-1-stimulated cell adhesion
HT29 Function Assay 1 μM 2 h suppresses the basal or IGF-1-stimulated cell adhesion
U87 Growth Inhibition Assay 25 nM 24 h increases DUSP10 knocked-down induced cell inhibition
AGS Cell Viability Assay 0-1000 nM 24/48 h decreases cell viability in time and dose dependent manner
MKN45 Cell Viability Assay 0-1000 nM 24/48 h decreases cell viability in time and dose dependent manner
MKN28 Cell Viability Assay 0-1000 nM 24/48 h decreases cell viability in time and dose dependent manner
KATO3 Cell Viability Assay 0-1000 nM 24/48 h decreases cell viability in time and dose dependent manner
SGC7901 Cell Viability Assay 0-1000 nM 24/48 h decreases cell viability in time and dose dependent manner
N87 Cell Viability Assay 0-1000 nM 24/48 h decreases cell viability in time and dose dependent manner
HMEC Cell Viability Assay 0-1000 nM 24/48 h decreases cell viability in time and dose dependent manner
HUVEC Cell Viability Assay 0-1000 nM 24/48 h decreases cell viability in time and dose dependent manner
MG63 Function Assay 50-1000 nM 0.5 h dose dependently (50–1000 nM) inhibits phosphorylation of Akt
U2OS  Function Assay 50-1000 nM 0.5 h dose dependently (50–1000 nM) inhibits phosphorylation of Akt
Saos-2  Function Assay 50-1000 nM 0.5 h dose dependently (50–1000 nM) inhibits phosphorylation of Akt
Saos-2 Function Assay 100 nM 0.5 h prevents osteosarcoma cell migration
MG63 Apoptosis Assay 100 nM 36 h promotes apoptosis
U2OS  Apoptosis Assay 100 nM 36 h promotes apoptosis
Saos-2  Apoptosis Assay 100 nM 36 h promotes apoptosis
DLD-1 Cell Viability Assay 0-1000 nM 24 h inhibits the growth in a dose-dependent manner
Caco2 Cell Viability Assay 0-1000 nM 24 h inhibits the growth in a dose-dependent manner
HT29 Cell Viability Assay 0-1000 nM 24 h inhibits the growth in a dose-dependent manner
H116 Cell Viability Assay 0-1000 nM 24 h inhibits the growth in a dose-dependent manner
Hct-8 Cell Viability Assay 0-1000 nM 24 h inhibits the growth in a dose-dependent manner
Colo320 Cell Viability Assay 0-1000 nM 24 h inhibits the growth in a dose-dependent manner
Sw948 Cell Viability Assay 0-1000 nM 24 h inhibits the growth in a dose-dependent manner
Colo205 Cell Viability Assay 0-1000 nM 24 h inhibits the growth in a dose-dependent manner
Colo320 Function Assay 1 μM 0-24 h abolishes the S6S235/236 but partially reduces the 4E-BP1T36/45
HT29 Function Assay 1 μM 0-24 h abolishes the S6S235/236 but partially reduces the 4E-BP1T36/45
Sw948 Function Assay 1 μM 0-24 h abolishes the S6S235/236 but partially reduces the 4E-BP1T36/45
DLD-1 Function Assay 1 μM 0-24 h abolishes the S6S235/236 but partially reduces the 4E-BP1T36/45
786-O Function Assay 0.1/0.5 μM 24 h increases E-cadherin mRNA levels dose dependently
786-O Function Assay 0-0.5 μM 24 h results in a dose dependent increase in E-cadherin protein expression 
OCI-AML3 Apoptosis Assay 2.5 μM 72 h induces apoptosis
Jurkat Function Assay 100/200/400 nM 18 h inhibits mTORC1-dependent S6 S235/236 phosphorylation
p210 BCR-Abl Function Assay 100/200/400 nM 18 h inhibits mTORC1-dependent S6 S235/236 phosphorylation
Jurkat Growth Inhibition Assay 400nM 24/48 h synergize with 17-AAG to suppress cell proliferation
p210 BCR-Abl Growth Inhibition Assay 400nM 24/48 h synergize with 17-AAG to suppress cell proliferation
8226 Function Assay 100-1000 nM 30 min activates ERK 
MM1.S  Function Assay 100-1000 nM 30 min activates ERK 
8226 Function Assay 0.5 μM 30 min induces activation of RAF and phosphorylation of MEK
MM1.S  Function Assay 0.5 μM 30 min induces activation of RAF and phosphorylation of MEK
MCF-7 Function Assay 50/200/500 nM 30 min dose-dependently (50–500 nM) suppresses phosphorylation of Akt
T47D Function Assay 50/200/500 nM 30 min dose-dependently (50–500 nM) suppresses phosphorylation of Akt
MDA-MB-231 Function Assay 50/200/500 nM 30 min dose-dependently (50–500 nM) suppresses phosphorylation of Akt
Bcap-37 Function Assay 50/200/500 nM 30 min dose-dependently (50–500 nM) suppresses phosphorylation of Akt
MCF-7 Apoptosis Assay 200 nM 36 h induces apoptosis
MDA-MB-231 Apoptosis Assay 200 nM 36 h induces apoptosis
Bcap-37 Apoptosis Assay 200 nM 36 h induces apoptosis
LS174T Function Assay 10/100/1000 nM 6 h inhibits mTORC1 activity by the dephosphorylation of S6 ribosomal protein
DLD-1  Function Assay 10/100/1000 nM 6 h inhibits mTORC1 activity by the dephosphorylation of S6 ribosomal protein
SW480 Function Assay 10/100/1000 nM 6 h inhibits mTORC1 activity by the dephosphorylation of S6 ribosomal protein
NIH 3T3 Function Assay 2 μM 18 h inhibits mTORC2 phosphorylation of Akt on Ser473 and mTORC1 phosphorylation of 4E-BP1 on Thr37/46
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
SW620  Function Assay 0.5/2 μM 4 h blocks all three mTOR outputs
PC12  Function Assay 40 nM induces lysosomal biogenesis and alleviated α-SYN accumulation 
DND-1 Growth Inhibition Assay 0.25/0.5/1 μM inhibits cell growth dose dependently
TMD8 Growth Inhibition Assay 0.25/0.5/1 μM inhibits cell growth dose dependently
Jurkat Growth Inhibition Assay 0.25/0.5/1 μM inhibits cell growth dose dependently
KOPT-K1 Growth Inhibition Assay 0.25/0.5/1 μM inhibits cell growth dose dependently
TMD7 Growth Inhibition Assay 0.25/0.5/1 μM inhibits cell growth dose dependently
THP-1 Growth Inhibition Assay 0.25/0.5/1 μM inhibits cell growth dose dependently
HT1376 Growth Inhibition Assay IC50=1.88 ± 1.1 μM
T24 Growth Inhibition Assay IC50=1.37 ± 0.4 μM
UM-UC-3 Growth Inhibition Assay IC50=0.63 ±0.1 μM
SW620 Growth Inhibition Assay IC50=7.8 μM
SW480 Growth Inhibition Assay IC50=4.6 μM
SK-CO-1 Growth Inhibition Assay IC50=4 μM
LS-513 Growth Inhibition Assay IC50=3.9 μM
SW1116 Growth Inhibition Assay IC50=0.84 μM
LS-174T Growth Inhibition Assay IC50=0.84 μM
HCT 116 Growth Inhibition Assay IC50=0.41 μM
HCT 15 Growth Inhibition Assay IC50=0.3 μM
COLO 205 Growth Inhibition Assay IC50=0.24 μM
HT-29 Growth Inhibition Assay IC50=0.23 μM
COLO 201 Growth Inhibition Assay IC50=0.23 μM
Caco-2 Growth Inhibition Assay IC50=0.22 μM
SW48 Growth Inhibition Assay IC50=0.09 μM
SW-48 Growth Inhibition Assay IC50=0.1 μM
HCT-15 Growth Inhibition Assay IC50=0.3 μM
HCT 116 Growth Inhibition Assay IC50=0.6 μM
SW620-R Growth Inhibition Assay IC50=1.3 μM
SK-CO-1 Growth Inhibition Assay IC50=2.1 μM
SW620 Growth Inhibition Assay IC50=11 μM
BaF3 Growth Inhibition Assay GI50=1.449 μM
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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. This compound displays some inhibitory activity against Ret, PKCα, PKCβ, and JAK2, while exhibits remarkable selectivity against 215 other protein kinases. Unlike rapamycin, this inhibitor inhibits both mTORC1 and mTORC2. In BT549 cells, this chemical 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] It potently inhibits PKCα with IC50 of 49 nM. Low concentrations of this compound inhibit the phosphorylation of Akt S473 and higher concentrations partially inhibit Akt T308-P in addition to S473-P. As this agent is a more effective mTORC1 inhibitor than rapamycin, it inhibits the proliferation of primary MEFs, and the phosphorylation of 4EBP1 at T36/45 and S65, more potently than rapamycin. This compound but not rapamycin potently inhibits cap-dependent translation, by causing a higher level of binding between 4EBP1 and eIF4E than rapamycin. [2] It 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. This inhibitor 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] It 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
Recombinant mTOR is incubated with this compound 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 this compound 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 S2218-WB1.gif 23991179
Growth inhibition assay Cell viability S2218-viability1.gif 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. This compound 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 of this chemical 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] This 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
  • https://pubmed.ncbi.nlm.nih.gov/18849971/
  • https://pubmed.ncbi.nlm.nih.gov/19209957/
  • https://pubmed.ncbi.nlm.nih.gov/20072130/
  • https://pubmed.ncbi.nlm.nih.gov/20686120/

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

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

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）

mg/kg g μL 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。

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よくある質問（FAQ）

質問1:
Do you have any suggestions about potential candidates for vehicles that we could use for in vivo studies?

回答
S2218 in the recommended solvent (30% PEG400 + 0.5% Tween80 + 5% Propylene glycol) is a suspension, and this formulation is for oral gavage. For IV injection, this compound can be dissolved in 2% DMSO+30% PEG 300+5% Tween 80+ddH2O at 5mg/ml as a clear solution.

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