Ceralasertib

SKU: orb1304309

Description

Ceralasertib (AZD6738) is a potent and selective orally active ATR kinase inhibitor with a reported IC50 of 1 nM. It demonstrates antitumor activity in preclinical research, being utilized in both in vitro and in vivo studies to investigate DNA damage response pathways and combination therapies in oncology.

Research Area

Molecular Biology, Signal Transduction

Key Properties

• CAS Number: 1352226-88-0
• MW: 412.51
• Purity: 99.71%
• Formula: C₂₀H₂₄N₆O₂S
• SMILES: C[C@@H]1COCCN1c1cc(nc(n1)-c1ccnc2[nH]ccc12)C1(CC1)S(C)(=N)=O
• Target: ATM/ATR
• Solubility: 10% DMSO+40% PEG300+5% Tween 80+45% Saline:7.6 mg/mL (18.42 mM);H2O:< 1 mg/mL (insoluble or slightly soluble);Ethanol:39 mg/mL (94.54 mM);DMSO:250 mg/mL (606.05 mM)

Bioactivity

• Target IC50:
  A549 cells:2 μM|PI3Kδ:6.8 μM|DYRK:10.8 μM|HT29 cells:2.6 μM (GI50)|DYRK (pS421):10.8 μM|ATR:1 nM
• In Vivo:
  METHODS: To assay anti-tumor activity in vivo Ceralasertib (10-50 mg/kg, 10% DMSO+40% Propylene Glycol+50% deionized water) was orally administered to LoVo, Granta-519, NCI-H23, or 549 xenograft-carrying athymic nude mice bearing LoVo, Granta-519, NCI-H23 or 549 xenografts once daily for 14-28 days. Results: LoVo and Granta-519 showed dose-dependent efficacy, with significant TGI at 50 mg/kg, moderate activity at 25 mg/kg, and no activity at 10 mg/kg . Significant antitumor activity was also observed in NCI-H23 but not in A549 model.
• In Vitro:
  METHODS: 276 different tumor cell lines were treated with Ceralasertib for 3 days and cell viability was measured by MTS assay. Results: For most cell lines the median GI50 for 50% growth Inhibition (1.47 µmol/L) was higher tha the IC90 for ATR cells, with only 13% o the cell lines having a GI50 belo the median, and 30% below 1 µmol/L. Hematological cell lines (median GI5 = 0.82 µmol/L) generally showed increased sensitivity compared to solid tumor cells (median GI5 = 1.68 µmol/L). METHODS: Colorectal cancer cells HT29 were treated with trifluridine (70 µM) and Ceralasertib (0.5 µM) for 48 h, an the expression levels of target proteins were measured by Western Blot. Results the trifluridine+Ceralasertib group inhibited Chk1 phosphorylation in HT29 cells at 48 h compared to the trifluridine group. Therefore, it was confirmed that Ceralasertib inhibited Chk1 phosphorylation. In HT29 and HCT116 cells, DNA damage was more severe in the trifluridine+Ceralasertib group than in the trifluridine group, which could be confirmed b the increased level of γH2A expression.
• Cell Research:
  Cells are treated in white walled, clear bottom 96-well plates wit the indicated doses of AZD6738, cisplatin, gemcitabine, or combination for 48 h. ATP levels are assessed as surrogate measure of viability was assessed usin the CellTiter-Glo Luminescent Cell Viability Assay and Safire 2 plate reader. Raw data are corrected for background luminescence prior to further analysis. For AZD6738 treatment, log dose response curves are generated in GraphPad Prism 6 by nonlinear regression (log inhibitor) vs. response with variable slope) of log-transformed (x = log(x)) data normalized to the mean of untreated controls. GI values, defined a the dose X at which Y = 50%, were extrapolated from dose response curves.

Storage & Handling

• Storage: keep away from moisture,store at low temperature,store under nitrogen | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Disclaimer: For research use only

Alternative Names

Ceralasertib, Ataxia telangiectasia mutated, ATM, ATM/ATR, ATM and RAD3 related, AZD 6738, AZD-6738, AZD6738, ATR, inhibit, Inhibitor

Compound Identifiers

PubChem CID

86660217