AZD8186

Catalog No.S7694 Batch:S769401

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Technical Data

Formula

C24H25F2N3O4
Molecular Weight 457.47 CAS No. 1627494-13-6
Solubility (25°C)* In vitro DMSO 91 mg/mL (198.92 mM)
Ethanol 35 mg/mL (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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description AZD8186 is a potent and selective inhibitor of PI3Kβ and PI3Kδ with IC50 of 4 nM and 12 nM, respectively. Phase 1.
Targets
PI3Kβ [1]
(Cell-free assay)		 PI3Kδ [1]
(Cell-free assay)		 PI3Kα [1]
(Cell-free assay)
4 nM 12 nM 35 nM
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]

Protocol (from reference)

Kinase Assay:[1]
  • 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.
Cell Assay:[2]
  • Cell lines

    A subset of cancer cell lines

  • Concentrations

    ~30 μM

  • Incubation Time

    72 hours

  • Method

    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.
Animal Study:[1]
  • Animal Models

    Nude mice bearing PTEN-deficient PC3 prostate tumor xenografts

  • Dosages

    100 mg/kg b.i.d

  • Administration

    p.o.

Selleck's AZD8186 has been cited by 17 publications

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

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.