VER-155008

製品コードS7751 バッチS775102

印刷

化学情報

Chemical Structure Synonyms Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C25H23Cl2N7O4
分子量 556.4 CAS No. 1134156-31-2
Solubility (25°C)* 体外 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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 VER155008は、HSP70、HSC70、およびGRP78（HSPA5、Bip）のセルフリーアッセイにおいて、それぞれ0.5 μM、2.6 μM、および2.6 μMのIC50を示す強力なHsp70ファミリー阻害剤であり、HSP90に対して100倍以上の選択性を示します。VER155008はautophagyを阻害し、HSP90クライアントタンパク質のレベルを低下させます。
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. In the 8505C and FRO cells, this compound reduces the cell viability and elevates the percentage of dead cells in a time- and dose- dependent manner. It causes a dose-dependent inhibition of cytokine-dependent AML cell proliferation. This chemical shows an effective inhibition of cell proliferation in A549 and H1975 cells.
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.

プロトコル(参考用のみ)

キナーゼアッセイ 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.
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.

参考

  • https://pubmed.ncbi.nlm.nih.gov/20012863/
  • https://pubmed.ncbi.nlm.nih.gov/25450359/
  • https://pubmed.ncbi.nlm.nih.gov/23586877/
  • https://pubmed.ncbi.nlm.nih.gov/24676905/
  • https://pubmed.ncbi.nlm.nih.gov/19256508/

カスタマーフィードバック

, , 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の高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

A chaperone-proteasome-based fragmentation machinery is essential for aggrephagy [ Nat Cell Biol, 2025, 27(9):1448-1464] PubMed: 40866512
Pharmacological Modulation of the Unfolded Protein Response as a Therapeutic Approach in Cutaneous T-Cell Lymphoma [ Biomolecules, 2025, 15(1)76] PubMed: 39858470
Shiga Toxin Type 2 Aggravates G1/S Phase Cell Cycle Arrest, Mediating Caspase-Independent Cell Death under Hyperosmotic Conditions in the Kidney [ J Microbiol Biotechnol, 2025, 35:e2508015] PubMed: 40915655
USP8 and Hsp70 regulate endoreplication by synergistically promoting Fzr deubiquitination and stabilization [ Sci Adv, 2025, 11(12):eadq9111] PubMed: 40106570
Caspase-2 is a condensate-mediated deubiquitinase in protein quality control [ Nat Cell Biol, 2024, 26(11):1943-1957] PubMed: 39482354
Impairment of lipid homeostasis causes lysosomal accumulation of endogenous protein aggregates through ESCRT disruption [ Elife, 2024, 12RP86194] PubMed: 39713930
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
Synergistic anticancer activity of HSP70 and HSF1 inhibitors in colorectal cancer cells: A new strategy for combination therapy [ Biochim Biophys Acta Mol Basis Dis, 2024, 1871(3):167630] PubMed: 39675530
Hsp70 Negatively Regulates Autophagy via Governing AMPK Activation, and Dual Hsp70-Autophagy Inhibition Induces Synergetic Cell Death in NSCLC Cells [ Int J Mol Sci, 2024, 25(16)9090] PubMed: 39201776
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

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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