Zelavespib (PU-H71)

別名:NSC 750424

Zelavespib (PU-H71, NSC 750424) is a potent and selective inhibitor of HSP90 with IC50 of 51 nM. Phase 1.

Zelavespib (PU-H71)化学構造

CAS No. 873436-91-0

サイズ 価格(税別) 在庫状況
10mM (1mL in DMSO) JPY 23200 国内在庫なし(納期7~10日)
JPY 18100 国内在庫あり
JPY 38500 国内在庫あり

代表番号: 045-509-1970|電子メール:[email protected]
よく尋ねられる質問

文献中Selleckの製品使用例(12)

カスタマーフィードバック1个实验数据

製品安全説明書

現在のバッチを見る: 純度: 99.03%
99.03

Zelavespib (PU-H71)関連製品

シグナル伝達経路

HSP (HSP90)阻害剤の選択性比較

Cell Data

Cell Lines Assay Type Concentration Incubation Time 活性情報 PMID
NCI-H526 cells Function assay 1 μM 24 h Binding affinity to HSP90 in human NCI-H526 cells at 1 uM after 24 hrs by fluorescence polarization assay 17603540
MCF7 cells Function assay 24 h Inhibition of Hsp90 in human MCF7 cells assessed as Her2 level after 24 hrs by Western blot, IC50=0.06 μM 18571929
NCI-H1299 cells Function assay 12 h Reduction in oxygen consumption rate in human NCI-H1299 cells incubated for 12 hrs 25383915
NCI-H69 cells Function assay 24 h Binding affinity to HSP90 in human NCI-H69 cells after 24 hrs by fluorescence polarization assay 17603540
NCI-N417 cells Function assay 24 h Binding affinity to HSP90 in human NCI-N417 cells after 24 hrs by fluorescence polarization assay 17603540
NCI-H187 cells Function assay 24 h Binding affinity to HSP90 in human NCI-H187 cells after 24 hrs by fluorescence polarization assay 17603540
NCI-H510 cells Function assay 24 h Binding affinity to HSP90 in human NCI-H510 cells after 24 hrs by fluorescence polarization assay 17603540
SKBR3 cells Function assay 24 h Binding affinity to HSP90 in human SKBR3 cells after 24 hrs by fluorescence polarization assay 17603540
H69AR cells Function assay 96 h Inhibition of HSP90-mediated antiapoptotic activity in human H69AR cells assessed as induction of cell growth arrest at 10 after 96 hrs by propidium iodide staining-based flow cytometry 17603540
NCI-H526 cells Function assay 24 h Binding affinity to HSP90 in human NCI-H526 cells after 24 hrs by fluorescence polarization assay 17603540
MDA-MB-468 cells Function assay Inhibitory activity against Hsp90 in human breast cancer MDA-MB-468 cell line, EC50=0.0102 μM 16392823
SKBr3 cells Growth inhibition assay Growth inhibition in human breast cancer SKBr3 cell line using SRB, IC50=0.05 μM 16392823
MRC5 cells Cytotoxicity assay Cytotoxicity against normal lung fibroblast MRC5 cell line, IC50=1 μM 16392823
他の多くの細胞株試験データをご覧になる場合はこちらをクリックして下さい

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.
特性 Purine-based, HSP90-selective inhibitor.
Targets
HSP90 [1]
51 nM
In Vitro
In vitro 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. PU-H71 (1 μM) kills 80%, 65%, and 80% of the initial population of MDA-MB-468, MDA-MB-231, and HCC-1806 cells, respectively. PU-H71 (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. PU-H71 induces apoptosis in TNBC in part by inactivation and downregulation of Akt and Bcl-xL. PU-H71 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 1μM PU-H71, respectively. PU-H71 markedly contains MDA-MB-231 cell invasion, with 90% suppression at 1 μM. [1] PU-H71 (2.5 μM) 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. PU-H71 (1 μM) 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. PU-H71 is able to induce apoptosis overcoming the resistance conferred by Bcl-2. [2] PU-H71 (30 n M) 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. PU-H71 displays similar effects on microglial cells as on astrocytes, with 50 nM PU-H71 needed to significantly reduce the LPS dependent nitrite release. [3]
Kinase Assay 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 tested Hsp90 inhibitor 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.
細胞実験 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 the 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.

実験結果図 Methods Biomarkers 結果図 PMID
Western blot AKT / c-Myc / pERK / RAF1 / EWS-FLI1 / IGF-1R / PDGFRA / c-KIT / SRC EGFR / HER3 / IGF-1R / c-Kit / Raf-1 / Akt / p90RSK / CSK / Hsp70 / Hsp90 Bcl-xl / p-PDK1 / p-AKT / cPARP LYN / SYK / BTK / AKT / MEK / ERK 24388362
Growth inhibition assay Cell viability 19416831
In Vivo
In Vivo 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. PU-H71 (75 mg/kg, 3 times per week) 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]
動物実験 動物モデル Human triple-negative breast cancers xenografts MDA-MB-231
投与量 75 mg/kg
投与経路 i.p. on an alternate day schedule
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT05612633 Withdrawn
Accelerated Phase MPN|Blast Phase MPN
Samus Therapeutics Inc.
June 15 2022 Phase 2
NCT03935555 Terminated
Primary Myelofibrosis (PMF)|Post-Polycythemia Vera Myelofibrosis (Post-PV MF)|Post-Essential Thrombocythemia Myelofibrosis (Post-ET MF)
Samus Therapeutics Inc.
August 12 2019 Phase 1
NCT03373877 Terminated
Myelofibrosis|Primary Myelofibrosis|Post-polycythemia Vera Myelofibrosis|Post-essential Thrombocythemia Myelofibrosis
Samus Therapeutics Inc.
May 24 2018 Phase 1
NCT01393509 Completed
Metastatic Solid Tumor|Lymphoma|Myeloproliferative Neoplasms (MPN)
Memorial Sloan Kettering Cancer Center
July 6 2011 Phase 1
NCT01581541 Terminated
Solid Tumors|Lymphoma
National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC)
April 26 2011 Phase 1

化学情報

分子量 512.37 化学式

C18 H21 I N6 O2 S

CAS No. 873436-91-0 SDF --
Smiles CC(C)NCCCN1C2=NC=NC(=C2N=C1SC3=C(C=C4C(=C3)OCO4)I)N
保管

In vitro
Batch:

DMSO : 100 mg/mL ( (195.17 mM); 吸湿したDMSOは溶解度を減少させます。新しいDMSOをご使用ください。)

Ethanol : 100 mg/mL

Water : 34 mg/mL

モル濃度計算器

in vivo
Batch:

Add solvents to the product individually and in order.

投与溶液組成計算機

実験計算

モル濃度計算器

質量 濃度 体積 分子量

投与溶液組成計算機(クリア溶液)

ステップ1:実験データを入力してください。(実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します)

mg/kg g μL

ステップ2:投与溶媒の組成を入力してください。(ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください)

% DMSO % % Tween 80 % ddH2O
%DMSO %

計算結果:

投与溶媒濃度: mg/ml;

DMSOストック溶液調製方法: mg 試薬を μL DMSOに溶解する(濃度 mg/mL, 注:濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法:Take μL DMSOストック溶液に μL PEG300,を加え、完全溶解後μL Tween 80,を加えて完全溶解させた後 μL ddH2O,を加え完全に溶解させます。

投与溶媒調製方法:μL DMSOストック溶液に μL Corn oil,を加え、完全溶解。

注意:1.ストック溶液に沈殿、混濁などがないことをご確認ください;
2.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

技術サポート

ストックの作り方、阻害剤の保管方法、細胞実験や動物実験の際に注意すべき点など、製品を取扱う時に問い合わせが多かった質問に対しては取扱説明書でお答えしています。

Handling Instructions

他に質問がある場合は、お気軽にお問い合わせください。

* 必須

大学・企業名を記入してください
名前を記入してください
電子メール・アドレスを記入してください 有効なメールアドレスを入力してください
お問い合わせ内容をご入力ください
Tags: Zelavespib (PU-H71)を買う | Zelavespib (PU-H71) ic50 | Zelavespib (PU-H71)供給者 | Zelavespib (PU-H71)を購入する | Zelavespib (PU-H71)費用 | Zelavespib (PU-H71)生産者 | オーダーZelavespib (PU-H71) | Zelavespib (PU-H71)化学構造 | Zelavespib (PU-H71)分子量 | Zelavespib (PU-H71)代理店