VER155008

Catalog No.S7751 Batch:S775104

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Technical Data

Formula

C25H23Cl2N7O4
Molecular Weight 556.4 CAS No. 1134156-31-2
Solubility (25°C)* In vitro DMSO 100 mg/mL (179.72 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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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 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]
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]

Protocol (from reference)

Kinase Assay:[1] [5]
  • 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 Assay:[1]
  • 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.
Animal Study:[1]
  • Animal Models

    HCT116 tumor bearing

  • Dosages

    40 mg/kg

  • Administration

    i.v.

Customer Product Validation

, , Neuroscience, 2014, 281C:164-177.

Data from [Data independently produced by , , Antiviral Res, 2018, 150:39-46]

Data from [Data independently produced by , , Cell Signal, 2017, 30:130-141]

Selleck's VER155008 has been cited by 47 publications

Caspase-2 is a condensate-mediated deubiquitinase in protein quality control [ Nat Cell Biol, 2024, 26(11):1943-1957] PubMed: 39482354
Small molecule inhibitor targeting the Hsp70-Bim protein-protein interaction in estrogen receptor-positive breast cancer overcomes tamoxifen resistance [ Breast Cancer Res, 2024, 26(1):33] PubMed: 38409088
HSP70 positively regulates translation by interacting with the IRES and stabilizes the viral structural proteins VP1 and VP3 to facilitate duck hepatitis A virus type 1 replication [ Vet Res, 2024, 55(1):63] PubMed: 38760810
Albumosomes formed by cytoplasmic pre-folding albumin maintain mitochondrial homeostasis and inhibit nonalcoholic fatty liver disease [ Signal Transduct Target Ther, 2023, 8(1):229] PubMed: 37321990
FACS-based genome-wide CRISPR screens define key regulators of DNA damage signaling pathways [ Mol Cell, 2023, 83(15):2810-2828.e6] PubMed: 37541219
HRS mediates tumor immune evasion by regulating proteostasis-associated interferon pathway activation [ Cell Rep, 2023, 10.1016/j.celrep.2023.113352] PubMed: 37948180
Single-cell trajectory analysis reveals a CD9 positive state to contribute to exit from stem cell-like and embryonic diapause states and transit to drug-resistant states [ Cell Death Discov, 2023, 9(1):285] PubMed: 37542044
Single-cell trajectory analysis reveals a CD9 positive state to contribute to exit from stem cell-like and embryonic diapause states and transit to drug-resistant states [ Cell Death Discov, 2023, 9(1):285] PubMed: 37542044
Single-cell trajectory analysis reveals a CD9 positive state to contribute to exit from stem cell-like and embryonic diapause states and transit to drug-resistant states [ Cell Death Discov, 2023, 9(1):285] PubMed: 37542044
Suboptimal Mitochondrial Activity Facilitates Nuclear Heat Shock Responses for Proteostasis and Genome Stability [ Mol Cells, 2023, 46(6):374-386] PubMed: 37077029

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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