受注:045-509-1970 |
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Synonyms | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C25H23Cl2N7O4 |
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分子量 | 556.4 | CAS No. | 1134156-31-2 | |
Solubility (25°C)* | 体外 | DMSO | 100 mg/mL warmed with 50ºC water bath (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. |
製品説明 | 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. |
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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] |
キナーゼアッセイ | Hsc70, Hsp70 and Grp78 fluorescence polarisation (FP) assay | |
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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. | ||
細胞アッセイ | 細胞株 | BT474, MB-468, HCT116, and HT29 cells |
濃度 | 50 μM | |
反応時間 | 72 h | |
実験の流れ | 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. | |
動物実験 | 動物モデル | HCT116 tumor bearing |
投薬量 | 40 mg/kg | |
投与方法 | i.v. |
, , 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]
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 |
A curcumin analogue GO-Y030 depletes cancer stem cells by inhibiting the interaction between the HSP70/HSP40 complex and its substrates [ FEBS Open Bio, 2023, none] | PubMed: 36648092 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
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