Home Cytoskeletal Signaling HSP inhibitor KW-2478

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KW-2478 HSP inhibitor

Cat.No.S2685

KW-2478 is a nonansamycin HSP90 inhibitor with IC50 of 3.8 nM. Phase 1.
KW-2478 HSP inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 574.66

Jump to Mechanism of Action Cell Culture & Working Concentration Solubility Chemical Information, Storage & Stability

Quality Control

Cell Culture, Treatment & Working Concentration

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
TC32 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells 29435139
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells 29435139
SJ-GBM2 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells 29435139
SK-N-MC qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-MC cells 29435139
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells 29435139
NB-EBc1 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells 29435139
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells 29435139
NB1643 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells 29435139
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
Rh18 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 cells 29435139
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells 29435139
Click to View More Cell Line Experimental Data

Chemical Information, Storage & Stability

Molecular Weight 574.66 Formula

C30H42N2O9

 Storage (From the date of receipt)
CAS No. 819812-04-9 Download SDF Storage of Stock Solutions

Synonyms N/A Smiles CCC1=C(C(=C(C=C1O)O)C(=O)C2=CC(=C(C=C2)OCCN3CCOCC3)OC)CC(=O)N(CCOC)CCOC

Solubility

In vitro
Batch:

DMSO : 115 mg/mL (200.11 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 3 mg/mL

Water : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
Batch:

In vivo Formulation Calculator (Clear solution)

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Working concentration: mg/ml;

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Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

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Mechanism of Action

Targets/IC50/Ki
HSP90 [1]
3.8 nM
In vitro
KW-2478 inhibits the binding of bRD to Hsp90α with IC50 of 3.8 nM. This compound degradates the Hsp90 client proteins, including FGFR3 and IGF-1Rβand c-Raf-1. It reduces the level of phosphorylated Erk1/2. This chemical induces apoptosis by cleavage of PARP, a substrate of caspase-3 In U266 cells,. It has Time dependency of antiproliferative activity, consecutive drug exposure for at least 12 hours is necessary to to exert potent antitumor activity. This agent downregulates the translocation products of IgH locus. It inhibits the transcription of c-Maf and cyclin D1 genes by mainly suppressing the function of Cdk9. [1] This compound has potent and broad growth inhibitory activities against various cell lines, it inhibites cancer cell growth in all cell lines, with EC50 of 101-252 nM, 81.4-91.4 nM and 120-622 nM for B-cell lymphoma, mantle cell lymphoma and multiple myeloma, respectively. It also shows potent growth inhibitory activity in primary CLL and NHL cells with EC50 of 40-170 nM and 200-400 nM, respectively. [2].
Kinase Assay
Hsp90 Binding Assay
Human Hsp90α solution (0.5 μg/mL) is fixed on 96-well plates, followed by blocking with TBS containing 1% bovine serum albumin. KW-2478 solutions is added to the wells, and bRD is added to a concentration of 0.1 μmol/L. After removal of solution, poly-HRP streptavidin solution dilutes with poly-HRP dilution buffer is added to the wells. After removal of solution, equal volumes of TMB peroxidase substrate and peroxidase solution B are added to the wells. To stop the HRP reaction, 2 mol/L H2SO4 are added, followed by measurement of absorbance at 450 nm using a microplate spectrophotometer.
In vivo
KW-2478 suppresses tumor growth and induces the degradation of client proteins in tumors in NCI-H929 s.c. inoculated model at doses of 100 mg/kg or more. This compound reduces both serum M protein and MM tumor burden in the bone marrow in OPM-2/GFP i.v. inoculated mouse model at doses of 100 mg/kg. [1]
References

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