Torkinib (PP242)

製品コードS2218 バッチS221807

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C16H16N6O
分子量 308.34 CAS No. 1092351-67-1
Solubility (25°C)* 体外 DMSO 62 mg/mL (201.07 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Torkinib (PP242)は、細胞を含まないアッセイでIC50が8 nMの選択的mTOR阻害剤であり、PI3KδまたはPI3Kα/β/γよりもそれぞれ10倍以上および100倍の選択性で両方のmTOR複合体を標的とします。Torkinib (PP242)はmitophagyとapoptosisを誘導します。
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. 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. 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. It is also more effective than rapamycin in achieving cytoreduction and apoptosis in multiple myeloma (MM) cells.
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. 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. This treatment potently inhibits the growth of 8226 cells in mice.
特徴 One of the first selective inhibitors that targets ATP domain of mTOR.

プロトコル(参考用のみ)

キナーゼアッセイ 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.
細胞アッセイ 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.
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
投薬量 ~60 mg/kg/day
投与方法 Oral gavage

参考

  • 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/

カスタマーフィードバック

Data from [Data independently produced by Mol Cancer Ther, 2014, 13(1), 37-48]

Data from [Data independently produced by Mol Cell Biol, 2014, 34(13), 2517-32]

Data from [Data independently produced by Cancer Res, 2013, 73(11), 3402-11]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

RANKL blockade inhibits cancer growth through reversing the tolerogenic profile of tumor-infiltrating (plasmacytoid) dendritic cells [ J Immunother Cancer, 2025, 13(3)e010753] PubMed: 40081943
DSCC1 restrains 53BP1/RIF1 signaling at DNA double-strand breaks to promote homologous recombination repair [ Cell Rep, 2025, 44(4):115452] PubMed: 40117291
Changes in Melanoma Cell Morphology Following Inhibition of Cell Invasion by Third-Generation mTOR Kinase Inhibitors [ Int J Mol Sci, 2025, 26(16)7770] PubMed: 40869090
mTORC1 restricts TFE3 activity by auto-regulating its presence on lysosomes [ Mol Cell, 2024, S1097-2765(24)00832-3] PubMed: 39486419
Akt enhances the vulnerability of cancer cells to VCP/p97 inhibition-mediated paraptosis [ Cell Death Dis, 2024, 15(1):48] PubMed: 38218922
The mevalonate pathway contributes to breast primary tumorigenesis and lung metastasis [ Mol Oncol, 2024, 10.1002/1878-0261.13716] PubMed: 39119789
WWP1 inhibition suppresses the proliferation of pancreatic cancer cells by regulating the PI3K-AKT pathway [ J Gastroenterol, 2024, 10.1007/s00535-024-02192-x] PubMed: 39656237
Casein kinase 1α mediates phosphorylation of the Merkel cell polyomavirus large T antigen for β-TrCP destruction complex interaction and subsequent degradation [ mBio, 2024, 15(8):e0111724] PubMed: 38940554
TRIM44, a Novel Prognostic Marker, Supports the Survival of Proteasome-Resistant Multiple Myeloma Cells [ Cells, 2024, 13(17)1431] PubMed: 39273003
Mcam stabilizes a luminal progenitor-like breast cancer cell state via Ck2 control and Src/Akt/Stat3 attenuation [ NPJ Breast Cancer, 2024, 10(1):80] PubMed: 39277578

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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