VE-821

- Overview
  - Please contact us at for specific academic pricing.
    
    Background
    
    VE-821 is a potent, highly-selective, and ATP-competitive DNA damage response (DDR) kinase ATR inhibitor with Ki value of 13nM. VE-821 specifically inhibits ATR, revealing low cross-reactivity against the mammalian target of rapamycin (mTOR), DNA-dependent protein kinase (DNA-PK), phosphoinositol 3-kinase-γ (PI3K) and the related PIKKs ATM [1].
    HL-60 cells treated with VE-821 (10μM) showed reduction of phosphorylatin of Chk1 (Ser 345), inhibition of cell growth, and a radiosensitizing effect after Gamma-ray irradiation [2].
    VE-821 has also been demonstrated to down-regulate the phosphorylated Chk1 (Ser 345) but it does not inhibit the phosphorylation of Chk2 (Thr68) and ATM (Ser1981) in pancreatic cancer cell lines, including PSN-1 and MiaPaCa-2 cells that are treated with gemcitabine or radiation. VE-821 combined with gemcitabine (a nucleoside analog) has caused a remarkable increase of cytotoxic effect of gemcitabine against hypoxia [3].
    
    [1] Reaper PM1, Griffiths MR, Long JM, Charrier JD, Maccormick S, Charlton PA, Golec JM, Pollard JR. Selective killing of ATM- or p53-deficient cancer cells through inhibition of ATR. Nat Chem Biol. 2011 Apr 13;7(7):428-30.
    [2] Vávrová J1, Zárybnická L, Lukášová E, Řezáčová M, Novotná E, Sinkorová Z, Tichý A, Pejchal J, Durišová K. Inhibition of ATR kinase with the selective inhibitor VE-821 results in radiosensitization of cells of promyelocytic leukaemia (HL-60). Radiat Environ Biophys. 2013 Nov;52(4):471-9.
    [3] Prevo R1, Fokas E, Reaper PM, Charlton PA, Pollard JR, McKenna WG, Muschel RJ, Brunner TB.The novel ATR inhibitor VE-821 increases sensitivity of pancreatic cancer cells to radiation and chemotherapy. Cancer Biol Ther. 2012 Sep;13(11):1072-81.
- Properties
  - Alternative Name
    
    2-(aminomethyl)-6-[4,6-diamino-3-[4-amino-3,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-2-hydroxycyclohexyl]oxyoxane-3,4,5-triol;sulfuric acid
    
    CAS Number
    
    1232410-49-9
    
    Molecular Formula
    
    C18H16N4O3S
    
    Molecular Weight
    
    368.41
    
    Purity
    
    98.69%
    
    Solubility
    
    ≥62.5 mg/mL in DMSO; insoluble in EtOH; insoluble in H2O
    
    Storage
    
    Store at -20°C
    
    * For Research Use Only
- Reference
  - 1. Jinghua Yu, Wenyan Zhang, et al. "Regulation of host factor γ-H2AX level and location by enterovirus A71 for viral replication." Virulence. 2022 Dec;13(1):241-257. PMID:35067196
    2. Yahya Benslimane, Thierry Bertomeu, et al. "Genome-Wide Screens Reveal that Resveratrol Induces Replicative Stress in Human Cells." Molecular Cell; Available online 4 August 2020.
    3. Shaj K, Hutcherson RJ, et al. "ATR Kinase Activity Limits Mutagenesis and Promotes the Clonogenic Survival of Quiescent Human Keratinocytes Exposed to UVB Radiation." Photochem Photobiol. 2019 Sep 25. PMID:31554014
    4. Jennifer Risso-Ballester, Rafael Sanjuán. "High Fidelity Deep Sequencing Reveals No Effect of ATM, ATR, and DNA-PK Cellular DNA Damage Response Pathways on Adenovirus Mutation Rate." Viruses 2019, 11(10), 938.
    5. KAVYA SHAJ. "DIFFERING FUNCTIONS OF ATR KINASE IN HUMAN EPIDERMAL KERATINOCYTES EXPOSED TO ULTRAVIOLET B RADIATION." Wright State University. 2019.
    6. Li Z, Liu B, et al. "hDNA2 nuclease/helicase promotes centromeric DNA replication and genome stability." EMBO J. 2018 May 17. pii: e96729. PMID:29773570
    7. Nanda Kumar Sasi, Flavie Coquel, et al. "DDK has a primary role in processing stalled replication forks to initiate downstream checkpoint signaling." bioRxiv. 2017.October 21.