|-- -- --|
|Solubility (25°C) *||In vitro||DMSO||15 mg/mL warmed (61.16 mM)|
|In vivo||5% DMSO+corn oil||2mg/mL|
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
|Description||KNK437 is a pan-HSP inhibitor, which inhibits the synthesis of inducible HSPs, including HSP105, HSP72, and HSP40.|
|In vitro||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.|
|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.|
|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).|
|Cell lines||COLO 320DM cells|
|Incubation Time||1 h|
|Method||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.|
|Animal Models||C3H/He mice|
Data from [Data independently produced by , , Br J Haematol, 2013, 161(5):667-76]
Western blots of lysates from BaF3 JAK2 V617F cells.
Data from [Data independently produced by , , ONCOLOGY REPORTS, 2012, 28:1953-1958.]
Secreted AMF levels measured with ELISA under hyperthermia with or without HSP inhibitors. AMF secretion was inhibited by hyperthermia and recovered to the level of the control by the addition of HSP27. Data are presented as the mean ± SD of 6 different experiments. a, control; b, hyperthermia; c, hyperthermia + 17-AAG; d, hyperthermia + KNK437; e, hyperthermia + KRIBB-III.
Inhibition of related JAK/STAT pathways with molecular targeted drugs shows strong synergy with ruxolitinib in chronic myeloproliferative neoplasm. [Barrio S, et al. Br J Haematol, 2013, 161(5):667-76]PubMed: 23560534
Hyperthermia reduces migration of osteosarcoma by suppression of autocrine motility factor. [Nakajima K, et al. Oncol Rep, 2012, 28(6):1953-8]PubMed: 23027359
PLEASE KEEP THE PRODUCT UNDER -20°C FOR LONG-TERM STORAGE.
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