PF-4708671

製品コードS2163 バッチS216350

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

C19H21F3N6
分子量 390.41 CAS No. 1255517-76-0
Solubility (25°C)* 体外 DMSO 30 mg/mL (76.84 mM)
Ethanol 8 mg/mL (20.49 mM)
Water Insoluble
* <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 PF-4708671 is a cell-permeable inhibitor of p70 ribosomal S6 kinase (S6K1 isoform) with Ki/IC50 of 20 nM/160 nM in cell-free assays, 400-fold greater selectivity for S6K1 than S6K2, and 4- and >20-fold selectivity for S6K1 than MSK1 and RSK1/2, respectively. First S6K1-specific inhibitor to be reported.
in vitro PF-4708671 is a piperazinyl-pyrimidine analogue and the first S6K1-specific inhibitor. PF-4708671 does not significantly inhibit the activity of the closely related S6K2 isoform or a number of other AGC kinases (Akt1, Akt2, PKA, PKCα, PKCϵ, PRK2, ROCK2, RSK1, RSK2 or SGK1) . PF-4708671 prevents the S6K1-mediated phosphorylation of S6 protein in response to IGF-1 (insulin-like growth factor 1), while having no effect upon the PMA-induced phosphorylation of substrates of the highly related RSK (p90 ribosomal S6 kinase) and MSK (mitogen- and stress-activated kinase) kinases. PF-4708671 is also found to induce phosphorylation of the T-loop and hydrophobic motif of S6K1, an effect that is dependent upon mTORC1 (mTOR complex 1). PF-4708671 does not affect activity of mTORC1. [1]

プロトコル(参考用のみ)

キナーゼアッセイ Protein kinase activity assays
For selectivity IC50 assays, purified active GST–S6K1, GST–S6K2, His–MSK1 (residues 2–802), His–RSK1 (residues 1–735) and His–RSK2 (residues 2–740) (0.5 units/mL) are assayed for 30 min at 30 °C in a 50 μL assay mixture in buffer A containing either 30 μM Crosstide (GRPRTSSFAEG, for S6K1, S6K2 and MSK1) or 30 μM Long S6 (KEAKEKRQEQIAKRRRLSSLRASTSKSGGSQK, for RSK1 and RSK2), 10 mM magnesium acetate and 100 μM [γ- 32P]ATP. Reactions are terminated and the incorporation of [γ-32P]phosphate into the peptide substrate is determined by applying the reaction mixture on to P81 phosphocellulose paper and scintillation counting after washing the papers in phosphoric acid. One unit of activity is defined as that which catalysed the incorporation of 1 nmol of [32P]phosphate into the substrate. To determine the Ki for PF-4708671, full-length recombinant S6K1 is added to a final concentration of 5 nM to Omnia assay buffer containing various concentrations of compound. The reaction is run for 60 min at 30 °C in a 50 μL assay volume. The fluorescence of the peptide is monitored at an excitation wavelength of 360 nm and an emission wavelength of 485 nm. The rate of the reaction at each compound concentration is normalized to the DMSO control rate, and this normalized rate against concentration is fitted to the Morrison tight-binding equation for a competitive inhibitor to provide the true Ki. In order to assay S6K activity in HEK-293 cell lysates, cells are lysed in Tris lysis buffer. Lysate (0.5 mg) is incubated with 5 μg of S6K antibody conjugated to Protein G–Sepharose for 1 h at 4 °C on a vibrating platform. Immunoprecipitates are washed twice with lysis buffer and twice with buffer A, and kinase activity is assayed exactly as described above using the Crosstide peptide.

カスタマーフィードバック

Data from [Data independently produced by PLoS One, 2014, 9(2), e90388]

Data from [Data independently produced by , , Front Immunol, 2017, 7:685]

Data from [Data independently produced by , , Mol Cancer Ther, 2015, 14(3): 799-809]

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：

STING Suppresses Mitochondrial VDAC2 to Govern RCC Growth Independent of Innate Immunity [ Adv Sci (Weinh), 2023, 10(3):e2203718] PubMed: 36445063
The translational oscillation in oocyte and early embryo development [ Nucleic Acids Res, 2023, 51(22):12076-12091] PubMed: 37950888
Pharmacological inhibition of S6K1 rescues synaptic deficits and attenuates seizures and depression in chronic epileptic rats [ CNS Neurosci Ther, 2023, 10.1111/cns.14475] PubMed: 37736829
mTORC1/ERK1/2 Interplay Regulates Protein Synthesis and Survival in Acute Myeloid Leukemia Cell Lines [ Biology (Basel), 2023, 12(5)676] PubMed: 37237490
Stress Granules determine the Development of Obesity-associated Pancreatic Cancer [ Cancer Discov, 2022, candisc.1672.2021] PubMed: 35674408
S6K1-mediated phosphorylation of PDK1 impairs AKT kinase activity and oncogenic functions [ Nat Commun, 2022, 13(1):1548] PubMed: 35318320
secDrug: a pipeline to discover novel drug combinations to kill drug-resistant multiple myeloma cells using a greedy set cover algorithm and single-cell multi-omics [ Blood Cancer J, 2022, 12(3):39] PubMed: 35264575
Sustained oncogenic signaling in the cytostatic state enables targeting of non-proliferating persistent cancer cells [ Cancer Res, 2022, can.21.2908] PubMed: 35792658
Acetyltanshinone IIA reduces the synthesis of cell cycle-related proteins by degrading p70S6K and subsequently inhibits drug-resistant lung cancer cell growth [ Pharmacol Res, 2022, 179:106209] PubMed: 35398238
Targeting glutamine metabolism network for the treatment of therapy-resistant prostate cancer [ Oncogene, 2022, 10.1038/s41388-021-02155-z] PubMed: 35046532

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。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。