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    Plinabulin (NPI-2358)
    Plinabulin (NPI-2358)

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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 #: V0683
    CAS #: 714272-27-2Purity ≥98%

    Description: Plinabulin (formerly also known as NPI-2358) is a novel and potent vascular disrupting agent (VDA) against tubulin-depolymerizing with IC50 of 9.8~18 nM in tumor cells. It demonstrate significant in vivo antitumor efficacy in human plasmacytoma mouse xenograft models. Plinabulin is a first-in-class and selective immunomodulating microtubule-binding agent (SIMBA), which binds in the vicinity of the colchicine binding domain of tubulin.

    References: Anticancer Drugs. 2006 Jan;17(1):25-31; Blood. 2011 May 26;117(21):5692-700.

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    Molecular Weight (MW)336.39
    CAS No.714272-27-2
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 54 mg/mL (160.5 mM)
    Water: <1 mg/mL
    Ethanol: <1 mg/mL
    SynonymsNPI-2358; Plinabulin; NPI2358; NPI 2358;  

    Chemical Name: (3E,6E)-3-benzylidene-6-((5-(tert-butyl)-1H-imidazol-4-yl)methylene)piperazine-2,5-dione

    SMILES Code: O=C(/C(NC/1=O)=C\C2=CC=CC=C2)NC1=C\C3=C(C(C)(C)C)NC=N3 

    Exact Mass: 336.15863 

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    In Vitro

    In vitro activity: NPI-2358 binds to the colchicine-binding site of tubulin and has potent inhibitory to human tumor cell lines which have overexpressed Pgp or reduced nuclear Topo II catalytic activity, with IC50 from 9.8 to 18 nM. NPI-2358 is able to rapidly induce tubulin depolymerization in HUVECs and monolayer permeability even at 20 nM. NPI-2358 induces cell death in MM cells with IC50 of 8-10 nM, which due to trigger early mitotic arrest in MM cells. NPI-2358 also inhibits tubule formation and migration of endothelial as well as MM cells, which leads to disrupt tumor vasculature. NPI-2358 could induces cell death in patient MM (CD138+) cells without effecting viability of normal mononuclear cells. Blockade of JNK abrogates NPI-2358-induced mitotic arrest or MM cell death.

    Cell Assay: The adherent cells (HT-29, PC-3, DU 145, MDA-MB-231, NCI-H292, Jurkat, MES-SA, MES-SA/Dx5, HL-60, HL-60/MX2.) are plated in 96-well flat-bottomed plates and allowed to attach for 24 hours at 37 °C. HL-60 and HL-60/MX2 cells are plated in 96-well plates on the day of NPI-2358 addition. Serially diluted NPI-2358 is added to cells at concentrations ranging from 2 pM to 20 μM. Cells treated with a final concentration of 0.25% (v/v) DMSO serves as the vehicle control. Cell viability is assessed 48 hours later by measuring the reduction of resazurin with a fluorimeter. The IC50 value is calculated.

    In VivoNPI-2358 (7.5 mg/kg) inhibits tumor growth in human plasmacytoma mouse xenograft models at well-tolerated doses. NPI-2358 induces a time- and dose-dependent decrease in tumour perfusion. NPI-2358 is more sensitive to the KHT sarcoma than the C3H tumour, while radiation response could enhance the antitumor activity in both models.
    Animal modelCDF1 mice or C3H/Hej mice. 
    Formulation & DosageDissolved  in a polyethylene glycol/solutol solution and diluted to the required concentration with 5% dextrose; 15 mg/kg; i.p. injection
    ReferencesAnticancer Drugs. 2006 Jan;17(1):25-31; Blood. 2011 May 26;117(21):5692-700; Int J Radiat Biol. 2011 Nov;87(11):1126-34. 

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

    Plinabulin (NPI-2358)

    Antivascular activity of plinabulin. Blood. 2011 May 26;117(21):5692-700.

    Plinabulin (NPI-2358)

    Cell death induced by plinabulin depends on JNK as well as caspases. Blood. 2011 May 26;117(21):5692-700.

    Plinabulin (NPI-2358)

    Plinabulin inhibits growth and triggers apoptosis in MM. Blood. 2011 May 26;117(21):5692-700. 


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