In Vivo (Add solvents to the product individually and in order.)
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.
Clear solution
10%DMSO
60%TEG
30%WFI
Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.
16.000mg/ml
(34.97mM)
Taking the 1 mL working solution as an example, add 100 μL of 160 mg/ml clarified DMSO stock solution to 600 μL of TEG, mix evenly to clarify it; then continue to add 300 μL of WFI to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
* <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.)
Preparing Stock Solutions
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 (Cell-free assay)
PI3Kδ (Cell-free assay)
PI3Kα (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. This compound shows preferred growth inhibition activity in most PTEN deficient cell lines with GI50 of <1 μM.
In Vivo
In nude mice bearing PTEN-deficient PC3 prostate tumour xenografts, AZD8186 (100 mg/kg, p.o.) strongly inhibits Akt phosphorylation levels, and causes significant tumour growth inhibition. When used in combination with ABT, this compound (60 mg/kg, p.o.) results in complete inhibition of tumour growth. In the mouse PTEN-null TNBC models HCC70 and MDA-MB-468, and the prostate models HID28, this chemical (50 mg/kg, p.o.) also inhibits the growth of tumours. Combination therapy using this compound with androgen deprivation results in long-lasting tumour regression, which persisted after treatment cessation.
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 pH 7.4, 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.
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.
Combined inhibition of CDK4/6 and AKT is highly effective against the luminal androgen receptor (LAR) subtype of triple negative breast cancer
[ Cancer Lett, 2024, 604:217219]
A high-content microscopy drug screening platform for regulators of the extracellular digestion of lipoprotein aggregates by macrophages
[ bioRxiv, 2024, 2024.09.26.615160]
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]
RETURN POLICY
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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.
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