| Name | KNK437 |
| Description | KNK437 (Heat Shock Protein Inhibitor I), a pan-HSP inhibitor, suppresses the synthesis of inducible HSPs(HSP105, HSP72, and HSP40). |
| Cell Research | 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.(Only for Reference) |
| Kinase Assay | Metabolic Labeling and Gel Electrophoresis: 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). |
| In vivo | KNK437 (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.[3] |
| Storage | Shipping with blue ice/Shipping at ambient temperature. |
| Solubility Information | 10% DMSO+90% Corn Oil : 1 mg/mL (4.08 mM), Sonication is recommended.
Ethanol : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 12 mg/mL (48.93 mM), Sonication is recommended.
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| Keywords | KNK-437 | KNK437 | KNK 437 | Inhibitor | inhibit | HSP72 | HSP40 | HSP105 | HSP | Heat shock proteins |
| Inhibitors Related | Ethoxyquin | Adezmapimod | Tamoxifen | Palmitic acid sodium | Mequinol | 7-Aminocephalosporanic acid | Benzbromarone | Elesclomol | Rifabutin | Palmitic acid | Tamoxifen Citrate | Isoxazole |
| Related Compound Libraries | Bioactive Compound Library | Endoplasmic Reticulum Stress Compound Library | Membrane Protein-targeted Compound Library | Anti-Breast Cancer Compound Library | Inhibitor Library | Metabolism Compound Library | Bioactive Compounds Library Max | Covalent Inhibitor Library | Preclinical Compound Library | Anti-Metabolism Disease Compound Library | Anti-Cancer Active Compound Library | Oxidation-Reduction Compound Library |
United States
