AZD8186

SKU: orb1300480

Description

AZD8186 is a potent and selective small molecule inhibitor of PI3Kβ and PI3Kδ isoforms, with IC50 values of 4 nM and 12 nM, respectively. It is a valuable research tool for studying PI3K signaling in oncology, particularly in PTEN-deficient cancers, and has been utilized in both in vitro and in vivo experimental models.

Research Area

Signal Transduction

Key Properties

• CAS Number: 1627494-13-6
• MW: 457.47
• Purity: 98.00%
• Formula: C₂₄H₂₅F₂N₃O₄
• SMILES: C[C@@H](Nc1cc(F)cc(F)c1)c1cc(cc2c1oc(cc2=O)N1CCOCC1)C(=O)N(C)C
• Target: PI3K
• Solubility: Ethanol:3 mg/mL (6.56 mM);H2O:< 1 mg/mL (insoluble or slightly soluble);10% DMSO+40% PEG300+5% Tween 80+45% Saline:3.3 mg/mL (7.21 mM);DMSO:84 mg/mL (183.62 mM)

Bioactivity

• Target IC50:
  PI3Kδ:12 nM|PI3Kβ:4 nM|PI3Kα:35 nM|PI3Kγ:675 nM
• 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. 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. Combination therapy using AZD8186 with androgen deprivation results in long-lasting tumor regression, which persisted after treatment cessation.
• 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. AZD8186 shows preferred growth inhibition activity in most PTEN deficient cell lines with GI50 of <1 μM.
• Cell Research:
  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)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

inhibit, Inhibitor, AZD 8186, AZD8186, AZD-8186, Phosphoinositide 3-kinase, PI3Kα, PI3Kβ, PI3Kδ, PI3Kγ, PI3K

Compound Identifiers

PubChem CID

52913813