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    InvivoChem Cat #: V0880
    CAS #: 218924-25-5Purity ≥98%

    Description: KNK437 (KNK-437; KNK 437; Heat Shock Protein Inhibitor I), a benzylidene lactam analog, is a novel and potent pan-HSP (heat shock proteins) inhibitor with potential antineoplastic activity. KNK-437 inhibited the acquisition of thermotolerance and the induction of various HSPs such as HSP105, HSP70, and HSP40 in a dose-dependent manner in COLO 320DM (human colon carcinoma) cells.

    References: Cancer Res. 2000;60(11):2942-8; Int J Hyperthermia. 2011;27(1):63-73; Clin Cancer Res. 2001;7(1):215-9.

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    Molecular Weight (MW)245.23
    CAS No.218924-25-5
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 15 mg/mL (61.2 mM)
    Water: <1 mg/mL
    Ethanol: <1 mg/mL
    Solubility (In vivo)Olive oil: 30 mg/mL

    Synonym: KNK437; KNK 437; KNK-437; 

    Chemical Name: (Z)-3-(benzo[d][1,3]dioxol-5-ylmethylene)-2-oxopyrrolidine-1-carbaldehyde


    InChi Code: InChI=1S/C33H41N5O6S2/c1-33(2,3)37-31(42)26-19-46-20-38(26)32(43)29(40)24(15-21-9-6-5-7-10-21)36-30(41)25(18-45-4)35-28(39)17-44-27-12-8-11-22-16-34-14-13-23(22)27/h5-14,16,24-26,29,40H,15,17-20H2,1-4H3,(H,35,39)(H,36,41)(H,37,42)/t24-,25-,26-,29-/m0/s1

    SMILES Code: O=CN1C(/C(CC1)=C\C2=CC=C(OCO3)C3=C2)=O

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    In Vitro

    In vitro activity: KNK437 dose-dependently inhibits the acquisition of thermotolerance and the induction of various HSPs including HSP105, HSP70, and HSP40 in COLO 320DM (human colon carcinoma) cells. KNK437 and quercetin inhibits thermotolerance in a dose-dependent manner in PC-3 cells. KNK437 decreases heat-induced accumulation of Hsp70 mRNA and protein in PC-3 and LNCaP cells

    Kinase Assay: COLO 320DM cells (200,000) are injected into each well of 12-well plastic plates 2 days before incubation in the presence of KNK437 for 1 h before heat shock. The cells are then heat-shocked at 42°C for 90 min or kept at 37°C for the same length of time and incubated at 37°C for 2 h. For metabolic labeling, cells are washed with PBS without Ca2+ or Mg2+ and incubated for 1 h with 1.22 MBq of [35S]methionine in 250 μL of methionine-free DMEM supplemented with 10% dialyzed fetal bovine serum. After metabolic labeling, cells are washed twice with PBS and lysed in a buffer containing 1% NP40, 0.15 M NaCl, 50 mM Tris-HCl (pH 8.0), 5 mM EDTA, and protease inhibitors [0.2 mM 4-(2-aminoethyl)benzenesulfonyl fluoride hydrochloride, 2 mM N-ethylmaleimide, 1 μg/mL pepstatin, and 1 μg/mL leupeptin]. After centrifugation at 12,000×g for 20 min, cell extracts containing equal amounts of trichloroacetic acid-insoluble radioactivity are analyzed by two-dimensional gel electrophoresis (the one-dimensional gel electrophoresis is a nonequilibrium pH gradient gel electrophoresis, and the two-dimensional gel electrophoresis is 10% SDS-PAGE).  

    Cell Assay: Thermotolerance is induced by incubating cells with 300 μM sodium arsenite for 90 min. Cells are preincubated with or without 100 μM KNK437 for 1 h before the sodium arsenite treatment. After treatment of the cells with sodium arsenite, cells are washed once with PBS and incubated at 37℃ for 5 h with or without KNK437. The effects of KNK437 on acquired thermotolerance are tested by heating the cells at 45°C for the indicated time. The surviving fraction is calculated as the plating efficiency of the treated cells divided by the plating efficiency of untreated control cells.

    In VivoKNK437 (200 mg/kg, i.p.) shows no antitumor effects and does not increase the thermosensitivity of nontolerant tumors. The same dose of KNK437 enhances the antitumor effects of fractionated heat treatment in a synergistic manner.
    Animal modelC3H/He mice
    Formulation & DosageDissolved in Olive oil; 200 mg/kg; i.p. injection

    Cancer Res. 2000 Jun 1;60(11):2942-8; Int J Hyperthermia. 2011;27(1):63-73; Clin Cancer Res. 2001 Jan;7(1):215-9.

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


    The effects of KNK437 on the bodyweights of tumor-free ICR mice. Clin Cancer Res. 2001 Jan;7(1):215-9. 


    The effect of KNK437 on tumors with a single heat treatment at 44°C for 30 min. Clin Cancer Res. 2001 Jan;7(1):215-9. 


    The effect of KNK437 on tumors with fractionated heat treatment. Clin Cancer Res. 2001 Jan;7(1):215-9.


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