PU-H71

製品コードS8039 別名:NSC 750424

PU-H71化学構造

分子量(MW):512.37

PU-H71 is a potent and selective inhibitor of HSP90 with IC50 of 51 nM. Phase 1.

サイズ 価格(税別)  
JPY 16102.00
JPY 36520.00

カスタマーフィードバック(1)

  • Effects of low-level HSP90 inhibition (by ganetespib, 2-5 nM; PU-H71, 40-70 nM) or febrile-range temperature (39 ℃) on HSP70 and HSP90 protein levels in FANCA wild-type cells. High-level HSP90 inhibition (ganetespib, 25 nM; PU-H71, 300 nM) as well as proteotoxic proteasomal inhibition (MG132, 2.5 mM) induced the expression of HSP70. Constitutive (upper band: C) and inducible forms (lower band: I) of HSP70 are indicated. HSP90 levels are shown for comparison.

    Cell, 2017, 168(5):856-866. PU-H71 purchased from Selleck.

製品安全説明書

HSP (e.g. HSP90)阻害剤の選択性比較

生物活性

製品説明 PU-H71 is a potent and selective inhibitor of HSP90 with IC50 of 51 nM. Phase 1.
特性 Purine-based, HSP90-selective inhibitor.
ターゲット
HSP90 [1]
51 nM
体外試験

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]

細胞データ
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
MDA-MB-468 cells M121V2Z2dmO2aX;uJIF{e2G7 NYDZb3JZUW6qaXLpeI9zgSCjY4Tpeol1gSCjZ3HpcpN1KEi|cEmwJIlvKGi3bXHuJIJz\WG|dDDjZY5k\XJiTVTBMW1DNTR4ODDj[YxtKGyrbnWsJGVEPTB;MD6wNVAzKM7:TR?= M4HBb|E3Ozl{OEKz
SKBr3 cells M4SxdGdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 NWfsOo54T3Kxd4ToJIlvcGmkaYTpc44hcW5iaIXtZY4h[nKnYYP0JINidmOncjDTT2JzOyClZXzsJIxqdmVidYPpcochW1KELDDJR|UxRTBwMEWg{txO NVfGeGRtOTZ|OUK4NlM>
MCF7 cells NIS4V5pHfW6ldHnvckBie3OjeR?= M2\lOVI1KGh? M1\uW2lvcGmkaYTpc44hd2ZiSIPwPVAhcW5iaIXtZY4hVUOINzDj[YxteyCjc4Pld5Nm\CCjczDI[ZIzKGyndnXsJIFnfGW{IEK0JIhzeyCkeTDX[ZN1\XKwIHLsc5QtKEmFNUC9NE4xPiEQvF2= NWrkcmtCOTh3N{G5Nlk>
MRC5 cells NY\EPFJZS3m2b4TvfIlkcXS7IHHzd4F6 MXrDfZRwfG:6aXPpeJkh[WejaX7zeEBvd3KvYXygcJVv\yCoaXLyc4Jt[XO2IF3SR|Uh[2WubDDsbY5mNCCLQ{WwQVEh|ryP M4S2dVE3Ozl{OEKz
NCI-H1299 cells MkP5SpVv[3Srb36gZZN{[Xl? MnzWNVIhcA>? M4TBXnJm\HWldHnvckBqdiCxeInn[Y4h[2:wc4XtdJRqd25icnH0[UBqdiCqdX3hckBPS0lvSEGyPVkh[2WubIOgbY5kfWKjdHXkJIZweiBzMjDodpM> MUiyOVM5OzlzNR?=
NCI-H69 cells NWLJR3d5TnWwY4Tpc44h[XO|YYm= MoT5NlQhcA>? MoTKRolv\GmwZzDh[oZqdmm2eTD0c{BJW1B7MDDpckBpfW2jbjDOR2kuUDZ7IHPlcIx{KGGodHXyJFI1KGi{czDifUBndHWxcnXzZ4Vv[2VicH;sZZJqgmG2aX;uJIF{e2G7 MYSxO|YxOzV2MB?=
NCI-N417 cells MkD1SpVv[3Srb36gZZN{[Xl? MYOyOEBp NWDzXFd{SmmwZHnu[{Bi\m[rbnn0fUB1dyCKU2C5NEBqdiCqdX3hckBPS0lvTkSxO{Bk\WyuczDh[pRmeiB{NDDodpMh[nliZnz1c5Jme2OnbnPlJJBwdGG{aYrheIlwdiCjc4PhfS=> NXHm[ZJWOTd4MEO1OFA>
NCI-H187 cells Ml;aSpVv[3Srb36gZZN{[Xl? MUKyOEBp NGS5fJlDcW6maX7nJIFn\mmwaYT5JJRwKEiVUEmwJIlvKGi3bXHuJG5EUS2KMUi3JINmdGy|IHHmeIVzKDJ2IHjyd{BjgSCobIXvdoV{[2WwY3WgdI9t[XKrenH0bY9vKGG|c3H5 M{HGSFE4PjB|NUSw
NCI-H510 cells M3vrO2Z2dmO2aX;uJIF{e2G7 MorTNlQhcA>? NFHkO3JDcW6maX7nJIFn\mmwaYT5JJRwKEiVUEmwJIlvKGi3bXHuJG5EUS2KNUGwJINmdGy|IHHmeIVzKDJ2IHjyd{BjgSCobIXvdoV{[2WwY3WgdI9t[XKrenH0bY9vKGG|c3H5 M2C0NlE4PjB|NUSw
SKBR3 cells M2TxbGZ2dmO2aX;uJIF{e2G7 MnfGNlQhcA>? MWfCbY5lcW6pIHHm[olvcXS7IITvJGhUWDlyIHnuJIh2dWGwIGPLRnI{KGOnbHzzJIFnfGW{IEK0JIhzeyCkeTDmcJVwemW|Y3XuZ4UheG:uYYLpfoF1cW:wIHHzd4F6 NH;WcWsyPzZyM{W0NC=>
NCI-H526 cells M1LyPWZ2dmO2aX;uJIF{e2G7 M2\Te|Eh|ryP MUCyOEBp NUHGTVNYSmmwZHnu[{Bi\m[rbnn0fUB1dyCKU2C5NEBqdiCqdX3hckBPS0lvSEWyOkBk\WyuczDheEAyKHWPIHHmeIVzKDJ2IHjyd{BjgSCobIXvdoV{[2WwY3WgdI9t[XKrenH0bY9vKGG|c3H5 NWW4XpV6OTd4MEO1OFA>
H69AR cells NVvsb4lPTnWwY4Tpc44h[XO|YYm= NYC4eXdnQTZiaB?= M4rkOGlvcGmkaYTpc44hd2ZiSGPQPVAudWWmaXH0[YQh[W62aXHwc5B1d3SrYzDhZ5Rqfmm2eTDpckBpfW2jbjDIOllCWiClZXzsd{Bie3Onc4Pl[EBieyCrbnT1Z5Rqd25ib3[gZ4VtdCCpcn;3eIgh[XK{ZYP0JIF1KDFyIHHmeIVzKDl4IHjyd{BjgSCycn;wbYRqfW1iaX;kbYRmKHO2YXnubY5oNWKjc3XkJIZtd3diY4n0c41mfHK7 M4PxfFE4PjB|NUSw
NCI-H526 cells MlHSSpVv[3Srb36gZZN{[Xl? NW\wOohIOjRiaB?= M3r2eWJqdmSrbnegZYZncW6rdImgeI8hUFOSOUCgbY4hcHWvYX6gUmNKNUh3Mk[gZ4VtdHNiYX\0[ZIhOjRiaILzJIJ6KG[udX;y[ZNk\W6lZTDwc4xiemm8YYTpc44h[XO|YYm= MY[xO|YxOzV2MB?=

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

体内試験 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]

お薦めの試験操作(参考用のみ)

キナーゼ試験:

[1]

+ 展開

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.
細胞試験:

[1]

+ 展開
  • 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.


    (参考用のみ)
動物試験:

[1]

+ 展開
  • 動物モデル: Human triple-negative breast cancers xenografts MDA-MB-231
  • 製剤: PBS
  • 投薬量: 75 mg/kg
  • 投与方法: i.p. on an alternate day schedule
    (参考用のみ)

溶解度 (25°C)

体外 DMSO 100 mg/mL (195.17 mM)
Ethanol 100 mg/mL (195.17 mM)
Water 34 mg/mL warmed (66.35 mM)

* 溶解度測定はSelleck技術部門によって行われており、その他文献に示されている溶解度と差異がある可能性がありますが、同一ロットの生産工程で起きる正常な現象ですからご安心ください。

化学情報

分子量 512.37
化学式

C18 H21 I N6 O2 S

CAS No. 873436-91-0
保管
in solvent
別名 NSC 750424

便利ツール

モル濃度計算器

モル濃度計算器

求めたい質量、体積または濃度を計算してください。

質量 (g) = 濃度 (mol/L) x 体積 (L) x 分子量 (g/mol)

モル濃度計算器方程式

  • 質量
    濃度
    体積
    分子量

*貯蔵液を準備するとき、常に、オンであるとわかる製品のバッチに特有の分子量を使って、を通してラベルとMSDS/COA(製品ページで利用可能な)。

希釈計算器

希釈計算器

貯蔵液を準備するために必要な希釈率を計算してください。Selleck希釈計算器は、以下の方程式に基づきます:

開始濃度 x 開始体積 = 最終濃度 x 最終体積

希釈の計算式

この方程式は、一般に略語を使われます:C1V1 = C2V2 ( 入力 出力 )

  • C1
    V1
    C2
    V2

常に貯蔵液を準備するとき、小びんラベルとMSDS/COA(オンラインで利用できる)で見つかる製品のバッチに特有の分子量を使ってください。

連続希釈計算器方程式

  • 連続希釈剤

  • 計算結果

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
分子量計算器

分子量计算器

そのモル質量と元素組成を計算するために、合成物の化学式を入力してください:

総分子量:g/mol

チップス: 化学式は大文字と小文字の区別ができます。C10H16N2O2 c10h16n2o2

モル濃度計算器

質量 濃度 体積 分子量

臨床試験

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03373877 Recruiting Myelofibrosis|Primary Myelofibrosis|Post-polycythemia Vera Myelofibrosis|Post-essential Thrombocythemia Myelofibrosis Samus Therapeutics Inc. May 24 2018 Phase 1
NCT03373877 Recruiting Myelofibrosis|Primary Myelofibrosis|Post-polycythemia Vera Myelofibrosis|Post-essential Thrombocythemia Myelofibrosis Samus Therapeutics Inc. May 24 2018 Phase 1
NCT03166085 Active not recruiting Metastatic Breast Cancer Memorial Sloan Kettering Cancer Center|Samus Therapeutics Inc. May 23 2017 Phase 1
NCT03166085 Active not recruiting Metastatic Breast Cancer Memorial Sloan Kettering Cancer Center|Samus Therapeutics Inc. May 23 2017 Phase 1
NCT01393509 Active not recruiting Metastatic Solid Tumor|Lymphoma|Myeloproliferative Neoplasms (MPN) Memorial Sloan Kettering Cancer Center July 2011 Phase 1
NCT01393509 Active not recruiting Metastatic Solid Tumor|Lymphoma|Myeloproliferative Neoplasms (MPN) Memorial Sloan Kettering Cancer Center July 2011 Phase 1

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

HSP (e.g. HSP90)シグナル伝達経路

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細胞株 試験類型 濃度 培養時間 溶剤類型 活性叙述 PMID