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    ZM 336372
    ZM 336372

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    This product is for research use only, not for human use. We do not sell to patients.
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    InvivoChem Cat #: V1009
    CAS #: 208260-29-1Purity ≥98%

    Description: ZM 336372 (ZM-336372; ZM336372) is a novel, potent and selective c-Raf kinase inhibitor with potential anticancer activity. It inhibits c-Raf with an IC50 of 70 nM, and shows 10-fold greater selectivity for c-RAF over B-RAF. It has no inhibitory effects against other kinases. ZM336372 has a different selectivity with the reported C-Raf inhibitor PD98059. When tested with primary neurons, ZM3363372 treatment decreased low potassium-induced apoptosis percent by inhibiting C-Raf activation. In tumor spheroids pretreated with H2O2 and ZM336372 for 24 hours totally abolished the ROS-induced eNOS up-regulation via mediating ERK1/2 signaling pathway.

    References: Chem Biol. 1999 Aug;6(8):559-68; Int J Cancer. 2003 Apr 10;104(3):274-82.

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    Molecular Weight (MW)389.45
    FormulaC23H23N3O3
    CAS No.208260-29-1
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 78 mg/mL (200.3 mM)
    Water: <1 mg/mL
    Ethanol: 2 mg/mL (5.1 mM)
    Other infoChemical Name: 3-(Dimethylamino)- N -[3-[(4-hydroxybenzoyl)-amino]-4-methylphenyl]benzamide
    InChi Key: PYEFPDQFAZNXLI-UHFFFAOYSA-N
    InChi Code: InChI=1S/C23H23N3O3/c1-15-7-10-18(24-23(29)17-5-4-6-19(13-17)26(2)3)14-21(15)25-22(28)16-8-11-20(27)12-9-16/h4-14,27H,1-3H3,(H,24,29)(H,25,28)
    SMILES Code: O=C(NC1=CC=C(C)C(NC(C2=CC=C(O)C=C2)=O)=C1)C3=CC=CC(N(C)C)=C3
    SynonymsZinc00581684; Zinc-00581684; Zinc 00581684; ZM336372 ZM-336372; ZM 336372


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    In Vitro

    In vitro activity: ZM 336372 shows 10-fold selectivity over B-Raf. ZM 336372 weakly inhibits SAPK2a/p38α and SAPK2b/p38β with IC50 of 2 μM, and is selective over 17 other protein kinases including PKA, PKC, AMPK, p42 MAPK, MKK1, SAPK1/JNK, and CDK1 even at the concentration of up to 50 μM. ZM 336372 does not prevent constitutive as well as growth factor or phorbol ester induced activation of MKKl or p42 MAPK/ERK2. Moreover, ZM 336372 dose not reverse the phenotype of Ras- or Raf-transformed cell lines. ZM 336372 treatment induces >100 activation of c-Raf and the B-Raf isoform, but it does not trigger any activation of MKKI or p42 MAPK/ERKP or induce any increase in the GTP-loading of Ras, suggesting that a feedback control loop exists by which Raf isoforms suppress their own activation, such that inhibition is always counterbalanced by reactivation. ZM 336372-induced activation of c-Raf is not prevented by inhibition of the MAPK cascade, protein kinase C or phosphatidylinositide 3-kinase.


    Kinase Assay: c-Raf kinase activity is assayed directly in Sl9 cell lysates. Human c-Raf is activated in Sf9 cells by cotransfection from baculovirus vectors containing DNA encoding v-Ras and Lck in the absence of ZM 336372. The cell lysates are then assayed for c-Raf activity in the presence of increasing concentrations of ZM 336372. 


    Cell Assay: Cells (H727 and BON) are exposed to various concentrations of ZM 336372 for 48 and 72 hours. After incubation, the medium is removed and cells are trypsinized. Cells are incubated on ice, and 2.5 μg/mL propidium iodide is added 5 minutes before flow cytometry. Data is acquired using a FACSCalibur benchtop flow cytometer using CellQuest acquisition and analysis software. Cytotoxicity is done using Cell Titer Glo Assay. Cell proliferation is measured using MTT assay.

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    Formulation & DosageN/A
    References

    Chem Biol. 1999 Aug;6(8):559-68; Int J Cancer. 2003 Apr 10;104(3):274-82.


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

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