PF-04691502

製品コードS2743 バッチS274306

印刷

化学情報

Synonyms

PF4691502

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₂₂H₂₇N₅O₄

分子量

425.48

CAS No.

1013101-36-4

Solubility (25°C)*

体外

DMSO

85 mg/mL (199.77 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	PF-04691502（PF4691502）は、ATP競合的なPI3K(α/β/δ/γ)/mTORデュアル阻害剤であり、セルフリーアッセイにおいてK_i値が1.8 nM/2.1 nM/1.6 nM/1.9 nMおよび16 nMですが、Vps34、AKT、PDK1、p70S6K、MEK、ERK、p38、またはJNKに対してはほとんど活性がありません。PF-04691502はapoptosisを誘導します。フェーズ2。
in vitro	PF-04691502 potently inhibits recombinant class I PI3K and mTOR in biochemical assays and suppresses transformation of avian fibroblasts mediated by wild-type PI3K γ, δ, or mutant PI3Kα. In PIK3CA-mutant and PTEN-deleted cancer cell lines, this compound reduces phosphorylation of AKT T308 and AKT S473 (IC(50) of 7.5-47 nM and 3.8-20 nM, respectively) and inhibits cell proliferation (IC(50) of 179-313 nM). It inhibits mTORC1 activity in cells as measured by PI3K-independent nutrient stimulated assay, with an IC(50) of 32 nM and inhibits the activation of PI3K and mTOR downstream effectors including AKT, FKHRL1, PRAS40, p70S6K, 4EBP1, and S6RP. Short-term exposure to this chemical predominantly inhibits PI3K, whereas mTOR inhibition persists for 24 to 48 hours. This compound induces cell cycle G(1) arrest, concomitant with upregulation of p27 Kip1 and reduction of Rb.
in vivo	Antitumor activity of PF-04691502 is observed in U87 (PTEN null), SKOV3 (PIK3CA mutation), and non-small cell lung carcinoma xenografts. This compound inhibits tumor growth at 7 days by 72%. FDG-PET imaging revealed that it reduces glucose metabolism dramatically. Tissue biomarkers of PI3K/mTOR pathway activity, p-AKT (S473), and p-RPS6 (S240/244), are also dramatically inhibited following its treatment.

プロトコル(参考用のみ)

キナーゼアッセイ	Kinase Assay
キナーゼアッセイ	The fluorescence polarization assay for ATP competitive inhibition is done as follows: mPI3Kα dilution solution (90 nM) is prepared in fresh assay buffer (50 mM Hepes pH 7.4, 150 mM NaCl, 5 mM DTT, 0.05% CHAPS) and kept on ice. The enzyme reaction contains 0.5 nM mouse PI3Kα (p110α/p85α complex purified from insect cells), 30 μM PIP2, PF-04691502 (0, 1, 4, and 8 nM), 5 mM MgCl₂, and 2-fold serial dilutions of ATP (0–800 μM). Final dimethyl sulfoxide is 2.5%. The reaction is initiated by the addition of ATP and terminated after 30 minutes with 10 mM EDTA. In a detection plate, 15 uL of detector/probe mixture containing 480 nM GST-Grp1PH domain and 12 nM TAMRA tagged fluorescent PIP3 in assay buffer is mixed with 15 uL of kinase reaction mixture. The plate is shaken for 3 minutes, and incubated for 35 to 40 minutes before reading on an LJL Analyst HT.
細胞アッセイ	細胞株	BT20, U87MG, and SKOV3 cells
	濃度	0-3 mM
	反応時間	3 days
	実験の流れ	BT20, U87MG, and SKOV3 cells are plated at 3,000 cell/well in 96-well culture plates in growth medium with 10% FBS. Cells are incubated overnight and treated with DMSO (0.1% final) or serial diluted this compound for 3 days. Resazurin is added to 0.1 mg/mL. Plates are incubated at 37 °C in 5% CO₂ for 3 hours. Fluorescence signals are read as emission at 590 nm after excitation at 530 nm. IC50 values are calculated by plotting fluorescence intensity to drug concentration in nonlinear curve
動物実験	動物モデル	LSL-Kras^G12D heterozygous mice (B6.129-Kras^tm4Tyj) and Pten^del mice (c;129S4-Pten^tm1Hwu/J), Orthotopic transplant of ovarian tumors
	投薬量	daily at either 7.5 or 10 mg/kg
	投与方法	Administered via oral gavage

参考

https://pubmed.ncbi.nlm.nih.gov/21750219/
https://pubmed.ncbi.nlm.nih.gov/21632463/
https://pubmed.ncbi.nlm.nih.gov/22684718/

カスタマーフィードバック

: Data from [Data independently produced by Mol Cancer Res, 2014, 12(10), 1520-31]

: Data from [Data independently produced by Toxicol Lett, 2013, 220(2), 150-6]

: , , Dr. Zhang of Tianjin Medical University

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：

ERK1-mediated GLYCTK2 phosphorylation promotes fructolysis to sustain glioblastoma survival under glucose deprivation [ Cell Death Discov, 2025, 11(1):266]	PubMed: 40467571
Inhibitor PF-04691502 works as a senolytic to regulate cellular senescence [ Exp Gerontol, 2024, 186:112359]	PubMed: 38184267
Zebrafish functional xenograft vasculature platform identifies PF-502 as a durable vasculature normalization drug [ iScience, 2023, 26(9):107734]	PubMed: 37680473
Functional restoration of lysosomes and mitochondria through modulation of AKT activity ameliorates senescence [ Exp Gerontol, 2023, 173:112091]	PubMed: 36657533
Glucose metabolic upregulation via phosphorylation of S6 ribosomal protein affects tumor progression in distal cholangiocarcinoma [ BMC Gastroenterol, 2023, 23(1):157]	PubMed: 37193984
RNF43G659fs is an oncogenic colorectal cancer mutation and sensitizes tumor cells to PI3K/mTOR inhibition [ Nature Communications, 2022, 3181-2022)]	PubMed: None
RNF43 G659fs is an oncogenic colorectal cancer mutation and sensitizes tumor cells to PI3K/mTOR inhibition [ Nat Commun, 2022, 13(1):3181]	PubMed: 35676246
A novel PI3K inhibitor XH30 suppresses orthotopic glioblastoma and brain metastasis in mice models [ Acta Pharm Sin B, 2022, 12(2):774-786]	PubMed: 35256946
Leveraging patient derived models of FGFR2 fusion positive intrahepatic cholangiocarcinoma to identify synergistic therapies [ NPJ Precis Oncol, 2022, 6(1):75]	PubMed: 36274097
Identification of New Vulnerabilities in Conjunctival Melanoma Using Image-Based High Content Drug Screening [ Cancers (Basel), 2022, 14(6)1575]	PubMed: 35326726

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。