Capivasertib

SKU: orb1307109

Description

Capivasertib

Research Area

Cell Biology, Signal Transduction

Key Properties

• CAS Number: 1143532-39-1
• MW: 428.92
• Purity: 99.02%
• Formula: C₂₁H₂₅ClN₆O₂
• SMILES: NC1(CCN(CC1)c1ncnc2[nH]ccc12)C(=O)N[C@@H](CCO)c1ccc(Cl)cc1
• Target: Autophagy,PKA,Akt,mTOR
• Solubility: DMSO:130 mg/mL (303.09 mM);Ethanol:1 mg/mL (2.33 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:8 mg/mL (18.65 mM);H2O:Insoluble

Bioactivity

• Target IC50:
  ROCK2:60 nM|Akt3:7 nM (cell free)|ROCK1:470 nM|p70 S6K:6 nM (cell free)|Akt1:3 nM (cell free)|PKA:7 nM (cell free)|Akt2:7 nM (cell free)
• In Vivo:
  METHODS: To assay antitumor activity in vivo, Capivasertib (100-300 mg/kg, 10% DMSO 25% w/v Kleptose HPB buffer) was administered by gavage twice daily for two weeks to nude mice harboring mammary cancer tumor BT474c. RESULTS: Capivasertib dose-dependently inhibited the growth of human tumor xenografts in vivo. METHODS: To assay antitumor activity in vivo, Capivasertib (100-300 mg/kg, 10% DMSO 25% w/v Kleptose HPB buffer) was administered by gavage to a PDGCX mouse model twice daily for twenty days. RESULTS: Capivasertib monotherapy resulted in 60% tumor growth inhibition.
• In Vitro:
  METHODS: Six strains of human gastric cancer cells were treated with Capivasertib (40 nM-50 µM) for 72 h. Cell viability was measured by SRB Assay. RESULTS: The IC50 of Capivasertib on HGS27, AGS, N87, SNU-1, MKN45, and MGC803 cells were 4.6/0.1/14.18/24.04/30.0/44.4 µM, respectively. METHODS: Breast cancer cells BT474c and prostate cancer cells LNCaP were treated with Capivasertib (0.03-10 µmol/L) for 2 h, and the expression levels of target proteins were detected by Western Blot. RESULTS: Capivasertib effectively inhibited the phosphorylation of S6 and 4E-BP1 in the cell lines, while it increased the phosphorylation of AKT at ser473 and thr308.
• Cell Research:
  A high-throughput screening cell-based assay was developed to measure cellular AKT activity using the MDA-MB-468 breast cancer cell line. Cells were exposed to AZD5363 at concentrations ranging from 3 to 0.003 μmol/L. After a 2-hour treatment, cells were fixed with formaldehyde, washed, permeabilized with 0.5% polysorbate 20 and then probed with a phospho-specific antibody against GSK3βser9. Levels of phosphorylated GSK3βser9 were measured with an Acumen Explorer laser scanning cytometer and IC50 values estimates by fitting data in Origin 7.0.
• Animal Research:
  When mean tumor sizes reached approximately 0.2 cm^3, the mice were randomized into control and treatment groups. The treatment groups received varying dose schedules of AZD5363 solubilized in a 10% DMSO 25% w/v Kleptose HPB buffer by oral gavage, docetaxel solubilized in 2.6% ethanol in injectable water by intravenous injection once on day 1 at 15 or 5 mg/kg once weekly. When administered in combination, docetaxel was administered 1 hour before the oral dose of AZD5363. The control group received the DMSO/Kleptose buffer alone, twice daily by oral gavage. Tumor volumes (measured by caliper), animal body weight, and tumor condition were recorded twice weekly for the duration of the study. Mice were sacrificed by CO2 euthanasia. The tumor volume was calculated (taking length to be the longest diameter across the tumor and width to be the corresponding perpendicular diameter) using the formula: (length × width) × √(length × width) × (π/6). Growth inhibition from the start of treatment was assessed by comparison of the differences in tumor volume between control and treated groups. Because the variance in mean tumor volume data increases proportionally with volume (and is therefore disproportionate between groups), data were log transformed to remove any size dependency before statistical evaluation. Statistical significance was evaluated using a one-tailed, 2-sample t-test.

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

Inhibitor, inhibit, mTOR (p70S6K), Akt, AZD 5363, Autophagy, AZD5363, AZD-5363, Akt1, Akt2, Akt3, Capivasertib, Protein kinase B, PKB, PKA

Compound Identifiers

PubChem CID

25227436

Petros A Tyrakis 1, Domen Kampjut 1, Georgina F Steele 1, H Jonathan G Lindström 1, Deborah Chirnomas 1, Benjamin D Hopkins 2, Marcus D Goncalves 3, Siddhartha Mukherjee 4, Lewis C Cantley 5, Oliver D K Maddocks 6 Multi-node inhibition targeting mTORC1, mTORC2 and PI3Kα potently inhibits the PI3K/AKT/mTOR pathway in endometrial and breast cancer models Br J Cancer ., (2025)

PubMed: 40360883