product name KNK437
Description: KNK437 is a novel and potent pan-HSP inhibitor, which inhibits the synthesis of inducible HSPs, including HSP105, HSP72, and HSP40. KNK437 is an effective radiosensitizer that targets multiple pro-survival stress response pathways. KNK437 is a useful agent for enhancing the efficiency of hyperthermic therapy which has less toxic side-effects in prostate cancer.
References: Cancer Res. 2000;60(11):2942-8; Int J Hyperthermia. 2011;27(1):63-73; Clin Cancer Res. 2001;7(1):215-9.
245.23
Formula
C13H11NO4
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
Synonyms
other peoduct :
| 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 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. |
| Animal model | C3H/He mice |
| Formulation & Dosage | Dissolved in Olive oil; 200 mg/kg; i.p. injection |
| References | 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. |
(R)-(+)-Etomoxir (sodium salt)
