Home Cell Cycle HSP (HSP90) inhibitor KNK437 For research use only.

KNK437

KNK437 is a pan-HSP inhibitor, which inhibits the synthesis of inducible HSPs, including HSP105, HSP72, and HSP40.

KNK437 Chemical Structure

KNK437 Chemical Structure

CAS No. 218924-25-5

Purity & Quality Control

KNK437 Related Products

Signaling Pathway

HSP (HSP90) Signaling Pathways

HSP (HSP90) Signaling Pathway

Biological Activity

Description KNK437 is a pan-HSP inhibitor, which inhibits the synthesis of inducible HSPs, including HSP105, HSP72, and HSP40.
Targets
HSP105 [1] HSP72 [1] HSP40 [1]
In vitro
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.[1] 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.[2]
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).
Cell Research Cell lines COLO 320DM cells
Concentrations 100 μM
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.
In Vivo
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]
Animal Research Animal Models C3H/He mice
Dosages 200 mg/kg
Administration i.p.

Chemical Information & Solubility

Molecular Weight 245.23 Formula

C13H11NO4
CAS No. 218924-25-5 SDF Download KNK437 SDF
Smiles C1CN(C(=O)C1=CC2=CC3=C(C=C2)OCO3)C=O
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 17 mg/mL ( (69.32 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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