VER155008

VER155008 is a potent Hsp70 family inhibitor with IC50 of 0.5 μM, 2.6 μM, and 2.6 μM in cell-free assays for HSP70, HSC70, and GRP78 (HSPA5, Bip), respectively, >100-fold selectivity over HSP90. VER155008 inhibits autophagy and causes reduced levels of HSP90 client proteins.

VER155008 Chemical Structure

VER155008 Chemical Structure

CAS: 1134156-31-2

Selleck's VER155008 has been cited by 41 publications

Purity & Quality Control

Batch: Purity: 99.96%
99.96

VER155008 Related Products

Choose Selective HSP (HSP90) Inhibitors

Cell Data

Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
BL21 DE3 Function assay 10 mins Inhibition of GRP78 (26 to 636 residues) (unknown origin) expressed in Escherichia coli BL21 DE3 cells pre-incubated for 10 mins before FITC-NRLLLTG fluorescent peptide addition in presence of 10 uM ADP followed by further incubation for 2 hrs by fluoresc, IC50=0.8μM 31129054
HCT116 Cytotoxicity assay Cytotoxicity against human HCT116 cells by SRB assay, GI50=5μM 19256508
HCT116 Antiproliferative assay Antiproliferative activity against human HCT116 cells, GI50=5μM 21526763
BT474 Function assay Binding affinity to Hsp70 nucleotide binding domain in human BT474 cells, IC50=10.4μM 20608738
HCT116 Function assay 24 hrs Inhibition of HSP70 in human HCT116 cells assessed as reduction of He2 protein levels after 24 hrs by Western blot 19256508
HCT116 Function assay 24 hrs Inhibition of HSP70 in human HCT116 cells assessed as reduction of Raf1 protein levels after 24 hrs by Western blot 19256508
Click to View More Cell Line Experimental Data

Biological Activity

Description VER155008 is a potent Hsp70 family inhibitor with IC50 of 0.5 μM, 2.6 μM, and 2.6 μM in cell-free assays for HSP70, HSC70, and GRP78 (HSPA5, Bip), respectively, >100-fold selectivity over HSP90. VER155008 inhibits autophagy and causes reduced levels of HSP90 client proteins.
Targets
HSP70 [1]
(Cell-free assay)
HSC70 [1]
(Cell-free assay)
GRP78 [1]
(Cell-free assay)
0.5 μM 2.6 μM 2.6 μM
In vitro
In vitro VER-155008 inhibits the proliferation of human breast and colon cancer cell lines BT474, MB-468, HCT116, and HT29 with GI50s in the range 5.3-14.4 μM, and induces Hsp90 client protein degradation in both HCT116 and BT474 cells.[1] In the 8505C and FRO cells, VER-155008 reduces the cell viability and elevates the percentage of dead cells in a time- and dose- dependent manner.[2] VER-155008 causes a dose-dependent inhibition of cytokine-dependent AML cell proliferation.[3] VER-155008 shows an effective inhibition of cell proliferation in A549 and H1975 cells. [4]
Kinase Assay Hsc70, Hsp70 and Grp78 fluorescence polarisation (FP) assay
The FP assay for Hsp70 is conducted in aqueous buffer consisting of 100 mM Tris pH 7.4, 150 mM KCl and 5 mM CaCl2, in a final assay volume of 100 µl, using 96 well black polystyrene high bind plates with a Fusion plate reader. N6-(6-amino)hexyl-ATP-5-FAM and the in-house protein preparation of GST-HSP70 3-382 have final concentrations in the assay of 20 nM and 400 nM, respectively. Compounds are tested as 10-point IC50s, with a final DMSO concentration of 5%. Assay mixtures are incubated for 3 h prior to reading on the Fusion (ex 485 nm; em 535 nm). The data is fitted using a 4 parameter logistical data model by XLFit 4. The FP assay for Hsc70 and Grp78 is carried out as described for Hsp70 using the same N6 -(6-amino)hexyl-ATP-5-FAM as the FP probe with the following modifications. For Hsc70, the protein and probe concentrations are 0.3 μM and 20 nM, respectively with a 30 min incubation at 22℃ while for Grp78, the protein and probe concentrations are 2 μM and 10 nM, respectively with a 2 h incubation at 22℃. The KD for the FAM-ATP probe was 0.24 μM for Hsc70 and 2 μM for Grp78.
Cell Research Cell lines BT474, MB-468, HCT116, and HT29 cells
Concentrations 50 μM
Incubation Time 72 h
Method All cell lines are grown in DMEM/10% FCS with GlutaMAX-I in a humidified atmosphere of 5% CO2 in air. Cell proliferation is determined using the sulforhodamine B (SRB) assay.
Experimental Result Images Methods Biomarkers Images PMID
Western blot Hsp70 / AR 28691182
Immunofluorescence Blimp-1 28842558
Growth inhibition assay Cell viability 28053100
In Vivo
In vivo In HCT116 tumor bearing mice, VER-155008 (25 or 40 mg/kg, i.v.) demonstrates rapid metabolism and clearance, along with tumor levels below the predicted pharmacologically active level.[1]
Animal Research Animal Models HCT116 tumor bearing
Dosages 40 mg/kg
Administration i.v.

Chemical Information & Solubility

Molecular Weight 556.4 Formula

C25H23Cl2N7O4

CAS No. 1134156-31-2 SDF Download VER155008 SDF
Smiles C1=CC(=CC=C1COCC2C(C(C(O2)N3C4=NC=NC(=C4N=C3NCC5=CC(=C(C=C5)Cl)Cl)N)O)O)C#N
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 100 mg/mL ( (179.72 mM); Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Water : Insoluble

Ethanol : Insoluble


Molecular Weight Calculator

In vivo
Batch:

Add solvents to the product individually and in order.


In vivo Formulation Calculator

Preparing Stock Solutions

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

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.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

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

Tel: +1-832-582-8158 Ext:3
If you have any other enquiries, please leave a message.

* Indicates a Required Field

Please enter your name.
Please enter your email. Please enter a valid email address.
Please write something to us.
Tags: buy VER155008 | VER155008 supplier | purchase VER155008 | VER155008 cost | VER155008 manufacturer | order VER155008 | VER155008 distributor