PIK-75 HCl

製品コードS1205 バッチS120502

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

C16H14BrN5O4S.HCl
分子量 488.74 CAS No. 372196-77-5
Solubility (25°C)* 体外 DMSO 3 mg/mL warmed with 50ºC water bath (6.13 mM)
Water Insoluble
Ethanol 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 PIK-75 HCl is a p110α inhibitor with IC50 of 5.8 nM (200-fold more potently than p110β), isoform-specific mutants at Ser773, and also potently inhibits DNA-PK with IC50 of 2 nM in cell-free assays.
in vitro PIK-75 shows the impressive potency and isoform selectivity at p110α while the corresponding IC50 values are 1300 nM, 76 nM and 510 nM for other PI3K isoforms, p110β, -γ, and -δ, respectively. Furthermore, when binding to purified p110α, PIK-75 is a noncompetitive inhibitor with respect to ATP with Ki of 36 nM and competitive with respect to the substrate PI with Ki of 2.3 nM. [1] PIK-75 also shows potent inhibition of DNA-PK. [2] PIK-75 (1 μM) reduces cell survival by significantly decreasing mitochondrial activity in unstimulated nonasthmatic airway smooth muscle (ASM) cells, asthmatic ASM cells, and lung fibroblasts. While in TGFβ-stimulated ASM cells, PIK75 only decreases mitochondrial activity in asthmatic cells without effects in nonasthmatic cells. [3] A recent study shows that PIK-75 (10 nM) inhibits TNF-α-induced CD38 mRNA expression and significantly attenuates of TNF-α-induced ADP-ribosyl cyclase activity in human airway smooth muscle cells. [4]
in vivo In the ErbB3WT tumor model, PIK-75 reduces in vitro chemotactic response to HRGβ1 and lowers pAkt levels by 40%. Besides, PIK-75 significantly reduces tumor cell motility and in vivo invasion in ErbB3WT primary tumors. [5] In the CD1 male mice, PIK-75 leads to serious impairments in the insulin tolerance test (ITT) and glucose tolerance test (GTT), and an increase in glucose production during a pyruvate tolerance test (PTT). [6]
特徴 PI3K and DNA-PK inhibitor.

プロトコル(参考用のみ)

キナーゼアッセイ Inhibition Assays
The PI3K inhibitor PIK-75 is dissolved at 10 mM in dimethyl sulfoxide and stored at −20°C until use. PI3K enzyme activity is determined in 50 μL of 20 mM HEPES, pH 7.5, and 5 mM MgCl2 containing 180 μM phosphatidyl inositol, with the reaction started by the addition of 100 μM ATP (containing 2.5 μCi of [γ-32P]ATP). After a 30-minute incubation at room temperature, the enzyme reaction is stopped by the addition of 50 μL of 1 M HCl. Phospholipids are then extracted with 100 μL of chloroform/methanol [1:1 (v/v)] and 250 μL of 2 M KCl followed by liquid scintillation counting. Inhibitors are diluted in 20% (v/v) dimethyl sulfoxide to generate a concentration versus inhibition of enzyme activity curve, which is then analyzed with the use of Prism version 5.00 for Windows to calculate the IC50. For kinetic analysis, a luminescent assay measuring ATP consumption is used. PI3K enzyme activity is determined in 50 μL of 20 mM HEPES, pH 7.5, and 5 mM MgCl2 with PI and ATP at various concentrations. After a 60-minute incubation at room temperature, the reaction is stopped by the addition of 50 μL of Kinase-Glo followed by a further 15-minute incubation. Luminescence is then read using a Fluostar plate reader. Results are analyzed using Prism.
細胞アッセイ 細胞株 A2780, A2780/cp70, 2780AD, HCT116, HT29, WIL, CALU-3, MCF7, PC3 and HS852 cells
濃度 0-10 μM
反応時間 48 hours
実験の流れ Mitochondrial activity is assessed after stimulation with TGFβ with or without inhibitors for 48 hours using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay. Harvested washed cells are resuspended in DMEM-lO% FCS and aliquoted (500 μL) into 24-well cluster plates prior to serial dilution (1:2) in duplicates. To each well, 100 μL of an appropriate MTT concentration (dissolved in PBS and filtered through a 0.2 μm filter before use to remove any blue formazan product) is added immediately after diluting the cells, which are then incubated for 3.5 hours at 37 °C. The resulting blue formazan product is solubilized overnight (16 hours) at 37 °C by the addition of 500 μL of 10% sodium dodecyl sulfate　(SDS) in 0.01 M HCl to each well. A sample (150　μL)　from each duplicate well is transferred to a 96-well　microplate, and the optical density determinedby automated spectrophotometry against a reagent blank (no　cells).　Absorbance is measured at a test wavelength of 570 nm and a reference wavelength of 690 nm. For each primary cell culture, results from three to six wells from each treatment are averaged, and data are expressed as absorbance 570 to 690 nm.
動物実験 動物モデル MTLn3 cells are injected into the right fourth mammary fat pad from the head of female severe-combined immunodeficient/NCr mice.
投薬量 ≤1 μM
投与方法 Administered via i.p.

カスタマーフィードバック

Data from [Data independently produced by Cell Death Differ, 2014, 21(3), 491-502]

Data from [Data independently produced by Cell Death Differ, 2014, 21(3), 491-502]

Data from [Data independently produced by J Pharmacol Exp Ther, 2014, 348(3), 432-41]

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：

PIK Your Poison: The Effects of Combining PI3K and CDK Inhibitors against Metastatic Cutaneous Squamous Cell Carcinoma In Vitro [ Cancers (Basel), 2024, 16(2)370] PubMed: 38254859
Pharmacological Targeting of Androgen Receptor Elicits Context-Specific Effects in Estrogen Receptor-Positive Breast Cancer [ Cancer Res, 2023, 83(3):456-470] PubMed: 36469363
MDM2 antagonists promote CRISPR/Cas9-mediated precise genome editing in sheep primary cells [ Mol Ther Nucleic Acids, 2023, 31:309-323] PubMed: 36726409
Reciprocal regulation of Daxx and PIK3CA promotes colorectal cancer cell growth [ Cell Mol Life Sci, 2022, 79(7):367] PubMed: 35718818
The Lectin LecB Induces Patches with Basolateral Characteristics at the Apical Membrane to Promote Pseudomonas aeruginosa Host Cell Invasion [ mBio, 2022, 13(3):e0081922] PubMed: 35491830
PIK-75 overcomes venetoclax resistance via blocking PI3K-AKT signaling and MCL-1 expression in mantle cell lymphoma [ Am J Cancer Res, 2022, 12(3):1102-1115] PubMed: 35411248
Identification of New Vulnerabilities in Conjunctival Melanoma Using Image-Based High Content Drug Screening [ Cancers (Basel), 2022, 14(6)1575] PubMed: 35326726
Isthmin-1 is an adipokine that promotes glucose uptake and improves glucose tolerance and hepatic steatosis [ Cell Metab, 2021, S1550-4131(21)00326-0] PubMed: 34348115
Response and resistance to CDK12 inhibition in aggressive B-cell lymphomas [ Haematologica, 2021, 10.3324/haematol.2021.278743] PubMed: 34162179
Transcriptional programming drives Ibrutinib-resistance evolution in mantle cell lymphoma [ Cell Rep, 2021, 34(11):108870] PubMed: 33730585

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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