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    InvivoChem Cat #: V0230
    CAS #: 905973-89-9Purity ≥98%

    Description: CGK 733 is a novel, potent and selective inhibitor of ATM (ataxia-telangiectasia mutated) and ATR (ATM and Rad3-related) with the potential to treat Hepatocellular carcinoma (HCC). It inhibits ATM/ATR with an IC50 of ~200 nM. CGK733 significantly enhanced taxol-induced cytotoxicity in HBV-positive HepG2.2.15 cells. CGK733 could potentially reverse the taxol resistance in HBV-positive HCC cells and may suggest a novel strategy to treat HBV-infected HCC patients. 

    References: Nat Chem Biol. 2006 Jul;2(7):369-74; Clin Cancer Res. 2008 Mar 15;14(6):1877-87.

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    Molecular Weight (MW)555.84
    CAS No.905973-89-9
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 100 mg/mL (179.9 mM)
    Water: <1 mg/mL
    Ethanol: <1 mg/mL
    Other infoChemical Name: 2,2-diphenyl-N-(2,2,2-trichloro-1-(3-(4-fluoro-3-nitrophenyl)thioureido)ethyl)acetamide
    InChi Code: InChI=1S/C23H18Cl3FN4O3S/c24-23(25,26)21(30-22(35)28-16-11-12-17(27)18(13-16)31(33)34)29-20(32)19(14-7-3-1-4-8-14)15-9-5-2-6-10-15/h1-13,19,21H,(H,29,32)(H2,28,30,35)
    SMILES Code: O=C(NC(NC(NC1=CC=C(F)C([N+]([O-])=O)=C1)=S)C(Cl)(Cl)Cl)C(C2=CC=CC=C2)C3=CC=CC=C3
    SynonymsCGK733; CGK-733; CGK 733

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    In Vitro

    In vitro activity: CGK733 is able to confer robust growth to senescent cells that have ceased proliferation. Senescence-associated β-galactosidase (SA–β-gal) activity disappears in CGK733-treated cells. CGK733 shows greater potency in inhibiting ATM/ATR than LY294002 (IC50 , ~5 μM for ATM and ATR), a pan-inhibitor of PI3K and PIKKs. CGK733 (30 μM) treated for 24h causes ~60% cell death in senescent MCF-7 cells. CGK733 (20 μM) induces the loss of cyclin D1 via the ubiquitin- dependent proteasomal degradation pathway in MCF-7 and T47D breast cancer cell lines. CGK733 at concentrations ranging from 0.6- 40 μM, inhibits proliferation of MCF-7 and T47D estrogen receptor (ER) positive breast cancer cells, MDA-MB436 ER negative breast cancer cells, LnCap pros-tate cancer cells and HCT116 colon cancer cells. Furthermore, CGK733 also suppresses proliferation of non- transformed mouse BALB/c 3T3 embryonic fibroblast cells. The CGK733-mediated inhibition of proliferation is dose dependent and significant at doses as low as 2.5 μM.

    Cell Assay: Cells are seeded in 96-well plates at a predetermined, optimal cell density to ensure exponential growth for duration of the assay. After a 24 h preincubation, growth medium is replaced with experimental medium containing the appropriate drug concentrations or 0.1% (v/v) vehicle control. After a 48 h incubation, cell proliferation is estimated using the sulforhodamine B colorimetric assay.

    In VivoCGK733 (25 mg/kg, i.p.) increases the ATM reporter activity (reports inactivation of ATM kinase activity) compared to control mice, with 2.4-fold, 3.1-fold, and 1.3-fold changes at 1, 4, and 8 hours, respectively
    Animal modelMice
    Formulation & Dosage25 mg/kg, i.p.
    ReferencesNat Chem Biol. 2006 Jul;2(7):369-74; Clin Cancer Res. 2008 Mar 15;14(6):1877-87.

    These protocols are for reference only. InvivoChem does not independently validate these methods.


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