AZD8186

製品コードS7694 バッチS769402

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

C24H25F2N3O4
分子量 457.47 CAS No. 1627494-13-6
Solubility (25°C)* 体外 DMSO 91 mg/mL warmed with 50ºC water bath (198.92 mM)
Ethanol 35 mg/mL warmed with 50ºC water bath (76.5 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 AZD8186 is a potent and selective inhibitor of PI3Kβ and PI3Kδ with IC50 of 4 nM and 12 nM, respectively. Phase 1.
in vitro AZD8186 potently inhibits p-Akt in MDA-MB-468 cells sensitive to PI3Kβ inhibition and Jeko B cells sensitive to PI3Kδ inhibition with IC50 of 3 nM and 4 nM, respectively. [1] AZD8186 shows preferred growth inhibition activity in most PTEN deficient cell lines with GI50 of <1 μM. [2]
in vivo In nude mice bearing PTEN-deficient PC3 prostate tumor xenografts, AZD8186 (100 mg/kg, p.o.) strongly inhibits Akt phosphorylation levels, and causes significant tumor growth inhibition. When used in combination with ABT, AZD8186 (60 mg/kg, p.o.) results in complete inhibition of tumor growth. [1] In the mouse PTEN-null TNBC models HCC70 and MDA-MB-468, and the prostate models HID28, AZD8186 (50 mg/kg, p.o.) also inhibits the growth of tumors. [2] Combination therapy using AZD8186 with androgen deprivation results in long-lasting tumor regression, which persisted after treatment cessation. [3]

プロトコル(参考用のみ)

キナーゼアッセイ PI3Kα, PI3Kβ, PI3Kγ and PI3Kδ enzyme assays
The inhibition of PI3Kα, PI3Kβ, PI3Kγ and PI3Kδ human recombinant PI3K isoforms is evaluated using a Kinase-Glo Plus Assay Kit. 12 point half-log concentration-response curves with a top concentration of 100 μM are constructed by dispensing DMSO solubilised compounds into white 384-well medium-binding microplates using an Echo 555. 3 μL of the appropriate PI3K in Tris buffer (50 mM Tris pH7.4, 0.05% CHAPS, 2.1 mM DTT, and 10 mM MgCl2) is added. The plate is covered and allowed to pre-incubate with compound for 20 minutes prior to addition of 3 μL of substrate solution containing PIP2 and ATP. The enzyme reaction is stopped after 80 minutes by the addition of Kinase Glo detection solution. Plates are covered and incubated for 30 minutes at room temperature before the luminescence signal is read using a PHERAstar plate reader. The final concentrations of DMSO, ATP and PIP2 in the assay are 2%, 8 μM, and 80 μM respectively. The final concentrations of PI3Kα, PI3Kβ, PI3Kγ and PI3Kδ are respectively 20 nM, 20 nM, 45 nM and 30 nM. For PI3Kα, PI3Kβ and PI3Kδ the concentration of active enzyme is determined as outlined in the enzyme assay tight binding limit determination section. For PI3Kγ the concentration of enzyme is determined by Bradford assay. IC50 values are calculated using Genedata Screener.
細胞アッセイ 細胞株 A subset of cancer cell lines
濃度 ~30 μM
反応時間 72 hours
実験の流れ Cells are seeded in 96-well plates, at a density to allow for logarithmic growth during the 72 hour assay, and incubated overnight at 37°C, 5% CO2. Cells are treated with AZD8186 (30 to 0.003 μM) for 72 hours and cell proliferation measured by MTS. The CellTiter Aqueous Non-Radioactive Cell Proliferation Assay reagent is used in accordance with the manufacturer’s protocol and Absorbance measured with Tecan Ultra instrument. Pre-dose measurements are made and the concentration needed to reduce the growth of treated cells to half that of untreated cells (GI50) values are determined.
動物実験 動物モデル Nude mice bearing PTEN-deficient PC3 prostate tumor xenografts
投薬量 100 mg/kg b.i.d
投与方法 p.o.

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：

Combination Treatment Targeting mTOR and MAPK Pathways Has Synergistic Activity in Multiple Myeloma [ Cancers (Basel), 2023, 15(8)2373] PubMed: 37190302
Cooperative Genomic Lesions in HRAS-Mutant Cancers Predict Resistance to Farnesyltransferase Inhibitors [ Res Sq, 2023, rs.3.rs-3154719] PubMed: 37503077
CDK/cyclin dependencies define extreme cancer cell-cycle heterogeneity and collateral vulnerabilities [ Cell Rep, 2022, 38(9):110448] PubMed: 35235778
Salmonella Promotes Its Own Survival in B Cells by Inhibiting Autophagy [ Cells, 2022, 11-132061] PubMed: 35805144
Vertical Inhibition of the RAF-MEK-ERK Cascade Induces Myogenic Differentiation, Apoptosis, and Tumor Regression in H/NRASQ61X Mutant Rhabdomyosarcoma [ Mol Cancer Ther, 2022, 21(1):170-183] PubMed: 34737198
Phenotypic Screening for Small Molecules that Protect β-Cells from Glucolipotoxicity [ ACS Chem Biol, 2022, 10.1021/acschembio.2c00052] PubMed: 35439415
Defining the therapeutic selective dependencies for distinct subtypes of PI3K pathway-altered prostate cancers [ Nat Commun, 2021, 12(1):5053] PubMed: 34417459
LLGL2 Increases Ca2+ Influx and Exerts Oncogenic Activities via PI3K/AKT Signaling Pathway in Hepatocellular Carcinoma [ Front Oncol, 2021, 11:683629] PubMed: 34178676
Y-box binding protein-1 is crucial in acquired drug resistance development in metastatic clear-cell renal cell carcinoma. [ J Exp Clin Cancer Res, 2020, 39(1):33] PubMed: 32041631
Targeting PI3Kβ alone and in combination with chemotherapy or immunotherapy in tumors with PTEN loss. [ Oncotarget, 2020, 17;11(11):969-981] PubMed: 32215185

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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