Zelavespib (PU-H71)

製品コードS8039 バッチS803902

印刷

化学情報

Chemical Structure Synonyms NSC 750424 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C18 H21 I N6 O2 S
分子量 512.37 CAS No. 873436-91-0
Solubility (25°C)* 体外 DMSO 100 mg/mL (195.17 mM)
Water (warmed with 50ºC water bath) 34 mg/mL (66.35 mM)
Ethanol (warmed with 50ºC water bath) 0.875 mg/mL (1.7 mM)
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <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 Zelavespib (PU-H71, NSC 750424) is a potent and selective inhibitor of HSP90 with IC50 of 51 nM. Phase 1.
in vitro Zelavespib (PU-H71) (1 μM) potently suppresses the growth of triple-negative breast cancers (TNBC) cell lines MDA-MB-468, MDA-MB-231, and HCC-1806 with IC50 of 65, 140 and 87 nM, respectively. This compound (1 μM) kills 80%, 65%, and 80% of the initial population of MDA-MB-468, MDA-MB-231, and HCC-1806 cells, respectively. It (0.25-1 μM) induces a dose-dependent degradation or inactivation of tumor driving molecules, including EGFR, IGF1R, HER3, c-Kit, Raf-1and Akt. Treatment for 24 h with 1 μM PU-H71, augments the percent of cells in G2-M phase of MDA-MB-468 to 69%, mediated by reduction in CDK1 and Chk1 expression. It induces apoptosis in TNBC in part by inactivation and downregulation of Akt and Bcl-xL. It leads to a proteasome-mediated reduction in IRAK-1 and TBK1 levels, resulting in approximately 84% and 90% reduction in NF-κB activity in MDA-MB-231 cells treated with 0.5 and 1 μM PU-H71, respectively. It markedly contains MDA-MB-231 cell invasion, with 90% suppression at 1 μM. [1] At 2.5 μM, it generates endoplasmic reticulum (ER) stress and activated the Unfolded Protein Response (UPR) as evidenced by XBP1 mRNA splicing (2.3-fold) and up-regulation of Grp94 (3.7-fold), Grp78 (4.9-fold), and CHOP (48-fold) protein expression and ATF4 (1.8-fold) mRNA expression. At 1 μM, it induces the mitochondrial pathway of apoptosis in HeLa cells, mediated by caspase but not calpain activation. In response to PU-H71-induced ER stress, apoptosis is triggered in melanoma, cervix, colon, liver and lung cancer cells, but not in normal human fibroblasts. It is able to induce apoptosis overcoming the resistance conferred by Bcl-2. [2] At 30 nM, it significantly reduces NOS2 activity (60% reduction) and expression in LI (1 μg/mL LPS and 5 ng/mL IFN γ)-stimulated astrocytes via inhibiting NF-κB element activation. It displays similar effects on microglial cells as on astrocytes, with 50 nM PU-H71 needed to significantly reduce the LPS dependent nitrite release. [3]
in vivo Zelavespib (PU-H71) administered at 75 mg/kg a.d. in the MDA-MB-231 model induces a 100% complete response, and tumors are reduced to scar tissue after 37 days of treatment, accompanied with reduction in many proliferative and anti-apoptotic molecules, namely an 80%, 95%, 99%, 80%, and 65% decrease in EGFR, HER3, Raf-1, Akt, and p-Akt, respectively. When administered at 75 mg/kg 3 times per week, this compound induces a 96% inhibition of tumor growth, accompanied by an 60% reduction in tumor cell proliferation, an 85% decline in activated Akt associated with survival and high invasive potential, and a 6-fold increase in apoptosis. [1]
特徴 Purine-based, HSP90-selective inhibitor.

プロトコル(参考用のみ)

キナーゼアッセイ HSP90 binding assay
Measurements are performed in black 96-well microtiter plates. Cell lysates are prepared by rupturing cellular membranes by freezing at -70℃ and dissolving the cellular extract in HFB [20 mM Hepes (K), pH 7.3, 50 mM KCl, 5 mM MgCl2, 20 mM Na2MoO4, 0.01% Nonidet P-40] with added protease and phosphatase inhibitors. Saturation curves are recorded in which fluorescently labeled geldanamycin (Cy3B-GM) (3 nM) is treated with increasing amounts of cellular lysates. The amount of lysate that results in polarization (mP) readings corresponding to 90%-99% bound ligand is chosen for the competition study. Here, each 96-well plate contains 3 nM Cy3B-GM, cellular lysate (amounts as determined and normalized to total Hsp90 as determined by Western blot analysis using Hsp90 purified from HeLa cells as standard) and Zelavespib (PU-H71) in a final volume of 100 μL. The plate is left for 24 h on a shaker at 4 ℃, and the fluorescence polarization (FP) values in mP are recorded. EC50 values are determined as the competitor concentrations at which 50% of the Cy3B-GM is displaced. FP measurements are performed on an Analyst GT microplate reader.
細胞アッセイ 細胞株 Human triple-negative breast cancers cell line MDA-MB-231
濃度 ~5μM
反応時間 3 days
実験の流れ

Exponentially growing MDA-MB-231 cells are seeded into black 96-well microtiter plates and incubated in medium containing either vehicle control (DMSO) or compounds for the indicated time at 37 ℃. Plates containing 3 replicate wells per assay condition are seeded at a density of 8×103 cells for each cell line in 100μL medium. After exposure of cells to Zelavespib (PU-H71) or other Hsp90 inhibitors, plates are equilibrated to room temperature (20-25 ℃) for approximately 30 min, and 100 μL CellTiter-Glo reagent are added to each well. Plates are mixed for 2 min on an orbital shaker and then incubated for 15 min to 2 h at room temperature. The luminescence signal in each well is measured in an Analyst GT microplate reader.
動物実験 動物モデル Human triple-negative breast cancers xenografts MDA-MB-231
投薬量 75 mg/kg
投与方法 i.p. on an alternate day schedule

参考

  • https://pubmed.ncbi.nlm.nih.gov/19416831/
  • https://pubmed.ncbi.nlm.nih.gov/23485394/
  • https://pubmed.ncbi.nlm.nih.gov/23123171/

カスタマーフィードバック

Data from [Data independently produced by , , Cell, 2017, 168(5):856-866]

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 patient-derived T cell lymphoma biorepository uncovers pathogenetic mechanisms and host-related therapeutic vulnerabilities [ Cell Rep Med, 2025, S2666-3791(25)00102-8] PubMed: 40147445
In Vivo Visualization and Quantification of Brain Heat Shock Protein 90 with [11C]HSP990 in Healthy Aging and Neurodegeneration [ J Nucl Med, 2025, jnumed.124.268961] PubMed: 40306968
BCL2 drives castration resistance in castration-sensitive prostate cancer by orchestrating reciprocal crosstalk between oncogenic pathways [ Cell Rep, 2025, 44(6):115779] PubMed: 40448998
Radiosynthesis and Evaluation of [18F]FEHSP990 as Novel PET Tracer for Hsp90 PET Imaging [ J Labelled Comp Radiopharm, 2025, 68(4):e4144] PubMed: 40219580
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
Epichaperome Inhibition by PU-H71-Mediated Targeting of HSP90 Sensitizes Glioblastoma Cells to Alkylator-Induced DNA Damage [ Cancers (Basel), 2024, 16(23)3934] PubMed: 39682123
High CD142 Level Marks Tumor-Promoting Fibroblasts with Targeting Potential in Colorectal Cancer [ Int J Mol Sci, 2023, 24(14)11585] PubMed: 37511344
Radiosynthesis and preclinical evaluation of [11C]SNX-ab as an Hsp90α,β isoform-selective PET probe for in vivo brain and tumour imaging [ EJNMMI Radiopharm Chem, 2023, 8(1):2] PubMed: 36715827
Development of a First-in-Class Small-Molecule Inhibitor of the C-Terminal Hsp90 Dimerization [ ACS Cent Sci, 2022, 8(5):636-655] PubMed: 35647282
BCL-xL inhibition potentiates cancer therapies by redirecting the outcome of p53 activation from senescence to apoptosis [ Cell Rep, 2022, 41(12):111826] PubMed: 36543138

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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