Capivasertib (AZD5363)
Catalog No.S8019
Molecular Weight(MW): 428.92
AZD5363 potently inhibits all isoforms of Akt(Akt1/Akt2/Akt3) with IC50 of 3 nM/8 nM/8 nM in cell-free assays, similar to P70S6K/PKA and lower activity towards ROCK1/2. Phase 2.
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HEK293T cells stably expressing mTOR mutants (H1968Y, P2213S, and S2215Y) were constructed by TALEN. After nutrient starvation, wild-type (WT, for HEK293T cells not expressing mutants but wild-type mTOR after TALEN edition and selection) or mutated HEK293T cells (heterozygous, A) were treated with indicated inhibitors or vehicle. The activation of indicated molecules was examined by Western blotting.
Clin Cancer Res, 2016, 22(4):1018-27. Capivasertib (AZD5363) purchased from Selleck.
G-H. Analysis of cells treated with AZD5363 (500 nM) for 24 hrs. G.Western analysis of whole cell lysates. H. Cells labeled with Annexin V-FITC for 6h were imaged. Individual points are average for replicates assessed in duplicate. Midlines are the average ± S.D. Student’s T-test.
Cancer Res, 2016, 76(16):4752-64.. Capivasertib (AZD5363) purchased from Selleck.
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Inhibition of PI3K and Akt by LY294002 and AZD5363 was confirmed by analyzing expression and activation status of the ribosomal protein S6 by Western blot analysis of PC-3 clone #14 cells treated with 0.5 or 5 uM AZD5363 (AZD) and 10 uM LY294002 (LY). Tubulin was used as a loading control.
Cell Commun Signal 2014 12(1), 61. Capivasertib (AZD5363) purchased from Selleck.
e HSP70 release induced by morphine was abrogated by AKT inhibitor. AZD5363 (AKT inhibitor, 2 μM) was given 15 min before morphine (200 μM, 12 h). Supernatants were collected and analyzed 12 h after morphine exposure (n = 3)
J Neuroinflammation, 2017, 14(1):228. Capivasertib (AZD5363) purchased from Selleck.
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(A) 239 cells stably expressing Flag-IL-17RA (293-IL-17RA cell line) were treated with 2 μM AZD5363 (a pan-Akt inhibitor) and/or 50 ng/ml insulin for the indicated time periods; Western blot analysis was performed for the indicated proteins; exogenous, IL-17RA transfected into 293 cells; endogenous, endogenous IL-17RA expressed in 293 cells.
Oncotarget, 2016, 7(12):13651-66. Capivasertib (AZD5363) purchased from Selleck.
LNCaP, LNCaP95, VCaP and 22Rv1 cells were transfected with control or pooled siRNA for AKT 1–3 isoforms for 36 hours. Cells were then further treated with 5 uM AZD5363 (B) for another 18 hours. Protein lysates were immunoblotted with AR (N-20), AR-V7, Pan-AKT, p-AKT(ser473) and β-Actin antibodies. Results were repeated in more than three independent experiments.
PLoS One 2014 9(10), e108780. Capivasertib (AZD5363) purchased from Selleck.
Purity & Quality Control
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Biological Activity
| Description | AZD5363 potently inhibits all isoforms of Akt(Akt1/Akt2/Akt3) with IC50 of 3 nM/8 nM/8 nM in cell-free assays, similar to P70S6K/PKA and lower activity towards ROCK1/2. Phase 2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Features | Moderate preclinical tolerability, and PD characteristics of an AKT inhibitor. Distinct profile from other AKT inhibitors in clinical development. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Targets |
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| In vitro |
AZD5363 is a potent Akt inhibitor with IC50 of 3 nM, 8 nM and 8 nM for Akt1, Akt2 and Akt3, respectively. [1] AZD5363 inhibits phosphorylation of AKT substrates in cells with a potency of approximately 0.3 to 0.8 μM. AZD5363 inhibits the proliferation of 41 of 182 solid and hematologic tumor cell lines with a potency of < 3 μM. [2] Activating mutations in PIK3CA, loss or inactivation of tumor suppressor PTEN, or HER2 amplification all are significantly predictive of responsiveness to AZD5363. Additionally, correlation is also seen between the RAS mutation status of cell lines and resistance to AZD5363. [1] |
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| Cell Data |
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| In vivo | Oral dosing of AZD5363 (100, 300 mg/kg) to nude mice causes dose- and time-dependent reduction of PRAS40, GSK3β, and S6 phosphorylation in BT474c xenografts, reversible increases in blood glucose concentrations, and dose-dependent decreases in 2[18F]fluoro-2-deoxy-d-glucose (18F-FDG) uptake in U87-MG xenografts. Chronic oral dosing of AZD5363 (130, 200, and 300 mg/kg) causes dose-dependent growth inhibition of xenografts derived from various tumor types, including HER2+ breast cancer models that are resistant to trastuzumab. AZD5363 also significantly enhances the antitumor activity of docetaxel, lapatinib, and trastuzumab in breast cancer xenografts. [2] |
Protocol
| Kinase Assay:[1] |
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Caliper Off-Chip Incubation Mobility Shift assay: The ability of AZD5363 and other compounds to inhibit the activity of AKT1, AKT2, and AKT3 is evaluated by the Caliper Off-Chip Incubation Mobility Shift assay. Active recombinant AKT1, AKT2, or AKT3 are incubated with a 5-FAM-labeled custom-synthesized peptide substrate together with increasing concentrations of inhibitor. Final reactions contained 1 to 3 nM AKT1, AKT2, or AKT3 enzymes; 1.5 mM peptide substrate; ATP at K m for each AKT isoform; 10 mM MgCl2, 4 mM DTT, 100 mM HEPES, and 0.015% Brij-35. The reactions are incubated at room temperature for 1 hour and stopped by the addition of buffer containing 100 mM HEPES, 0.015% Brij-35 solution, 0.1% coating reagent, 40 mM EDTA, and 5% DMSO. Plates are then analyzed using a Caliper LC3000, allowing for separation of peptide substrate and phosphorylated product by electrophoresis with subsequent detection and quantification of laser induced fluorescence. |
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| Cell Research: [2] |
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| Animal Research:[2] |
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Solubility (25°C)
| In vitro | DMSO | 86 mg/mL (200.5 mM) |
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| Water | Insoluble | |
| Ethanol | Insoluble | |
| In vivo | Add solvents to the product individually and in order(Data is from Selleck tests instead of citations): 1% CMC Na For best results, use promptly after mixing. |
30mg/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
| Molecular Weight | 428.92 |
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| Formula | C21H25ClN6O2 |
| CAS No. | 1143532-39-1 |
| Storage | powder |
| in solvent | |
| Synonyms | N/A |
Bio Calculators
Molarity Calculator
Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:
Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)
*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).
Dilution Calculator
Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )
* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).
Molecular Weight Calculator
Enter the chemical formula of a compound to calculate its molar mass and elemental composition:
Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2
Instructions to calculate molar mass (molecular weight) of a chemical compound:
To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.
Definitions of molecular mass, molecular weight, molar mass and molar weight:
Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.
Molarity Calculator
Clinical Trial Information
| NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
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| NCT03772561 | Recruiting | Solid Tumor Adult | National University Hospital Singapore | December 3 2018 | Phase 1 |
| NCT03772561 | Recruiting | Solid Tumor Adult | National University Hospital Singapore | December 3 2018 | Phase 1 |
| NCT03310541 | Recruiting | Breast Cancer|Prostate Cancer|Advanced Solid Tumors | Memorial Sloan Kettering Cancer Center | October 11 2017 | Phase 1 |
| NCT03310541 | Recruiting | Breast Cancer|Prostate Cancer|Advanced Solid Tumors | Memorial Sloan Kettering Cancer Center | October 11 2017 | Phase 1 |
| NCT03182634 | Recruiting | Advanced Breast Cancer | Institute of Cancer Research United Kingdom|Royal Marsden NHS Foundation Trust | December 15 2016 | Phase 2 |
| NCT03182634 | Recruiting | Advanced Breast Cancer | Institute of Cancer Research United Kingdom|Royal Marsden NHS Foundation Trust | December 15 2016 | Phase 2 |
Tech Support
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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