KNK437 inhibit stress-induced synthesis of heat shock proteins (HSPs). KNK437 (100 μM) inhibits thermotolerance in COLO 320DM cells after the first heat treatment. KNK437 shows inhibitory effects on thermotolerance dose-dependently in COLO 320DM cells (0-200 μM) and HeLa S3 cells (100, 200 μM).
In vivo, KNK437 (62.5-400 mg/kg) recovers bodyweight losses of tumor-free CD-1 (ICR) mice. KNK437 (200 mg/kg) alone shows no antitumor effects and does not increase the thermosensitivity of nontolerant tumors.
|Cell lines||COLO 320DM cells|
|Preparation method||Cells (1 × 105) are seeded in the flasks, incubated at 37°C for 48 h, and then heated by immersing the flasks in a water bath (45°C ± 0.05°C). KNK437 and quercetin are dissolved in DMSO before being added at the indicated concentrations. The final concentration of DMSO in each culture medium is 0.25% (v/v), irrespective of the concentrations of the drugs. The same concentration of DMSO is used as a control. Sodium arsenite is dissolved in PBS at a concentration of 80 mM and added to the medium. Cells are treated with 300 μM sodium arsenite at 37°C for 1.5 h, rinsed, and then incubated at 37°C for 5 h before 45°C heat challenge.|
|Concentrations||0, 25, 50, 100, 150, and 200 μm|
|Animal models||tumor-free CD-1 (ICR) mice|
|Formulation||dissolved in olive oil|
|Dosages||62.5 to 500 mg/kg|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
|Solubility||DMSO: ≥ 25 mg/mL|
|Related HSP Products|
Calenduloside E (CE) is a natural pentacyclic triterpenoid saponin extracted from Aralia elata. Calenduloside E (CE) has anti-apoptotic potent by targeting heat shock protein 90 (Hsp90).
HM03 is a potent and selective HSPA5 inhibitor with anticancer activity.
Cucurbitacin D induces apoptosis through caspase-3 and phosphorylation of JNK in hepatocellular carcinoma cells.
Arimoclomol maleate (also known as BRX-220) is a heat shock protein amplifier, and is potentially useful for the treatment of Niemann-Pick disease type C (NP-C).
JG-98 is an allosteric heat shock protein 70 (Hsp70) inhibitor, which binds tightly to a conserved site on Hsp70 and disrupts the Hsp70-Bag3 interaction.
Products are for research use only. Not for human use. We do not sell to patients.
© Copyright 2010-2020 AbMole BioScience. All Rights Reserved.