AZD8186

Name: AZD8186
Brand: Selleck Chemicals
SKU: S7694
Rating: 5 (8 reviews)

For research use only.

Catalog No.S7694

8 publications

Molecular Weight(MW): 457.47

AZD8186 is a potent and selective inhibitor of PI3Kβ and PI3Kδ with IC50 of 4 nM and 12 nM, respectively. Phase 1.

Selleck's AZD8186 has been cited by 8 publications

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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

Kinase Assay:^[1]	- Collapse 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 Research:^[2]	- Collapse 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. (Only for Reference)
Animal Research:^[1]	- Collapse Animal Models: Nude mice bearing PTEN-deficient PC3 prostate tumor xenografts Dosages: 100 mg/kg b.i.d Administration: p.o. (Only for Reference)

References

Solubility (25°C)

In vitro	DMSO	91 mg/mL warmed (198.92 mM)
	Ethanol	35 mg/mL warmed (76.5 mM)
	Water	Insoluble
In vivo	Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 10% DMSO + 60% TEG+ 30% WFI For best results, use promptly after mixing.	16mg/mL

* 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.

Chemical Information Download AZD8186 SDF

Molecular Weight	457.47
Formula	C₂₄H₂₅F₂N₃O₄
CAS No.	1627494-13-6
Storage	3 years-20°C powder 2 years-80°C in solvent
Synonyms	N/A
Smiles	CC(NC1=CC(=CC(=C1)F)F)C2=CC(=CC3=C2OC(=CC3=O)N4CCOCC4)C(=O)N(C)C

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Method for preparing DMSO master liquid: ： mg drug pre-dissolved in μL DMSO (Master liquid concentration mg/mL， Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation：Take DMSO master liquid, next addμL PEG300， mix and clarify, next addμL Tween 80，mix and clarify, next add μL ddH₂O，mix and clarify.

Note：1.Please make sure the liquid is clear before adding the next solvent.
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Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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PI3K Signaling Pathway Map

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AZD8186