PU-H71

Catalog No.S8039 Synonyms: NSC 750424

PU-H71 Chemical Structure

Molecular Weight(MW): 512.37

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

Size Price Stock Quantity  
USD 97 In stock
USD 220 In stock
Bulk Discount

Free Overnight Delivery on orders over $ 500
Next day delivery by 10:00 a.m. Order now.

1 Customer Review

  • 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.

Purity & Quality Control

Choose Selective HSP (e.g. HSP90) Inhibitors

Biological Activity

Description PU-H71 is a potent and selective inhibitor of HSP90 with IC50 of 51 nM. Phase 1.
Features Purine-based, HSP90-selective inhibitor.
Targets
HSP90 [1]
51 nM
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]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
MDA-MB-468 cells M2nBPGZ2dmO2aX;uJIF{e2G7 MX7Jcohq[mm2b4L5JIFkfGm4aYT5JIFo[Wmwc4SgTJNxQTBiaX6gbJVu[W5iYoLlZZN1KGOjbnPldkBOTEFvTVKtOFY5KGOnbHygcIlv\SxiRVO1NF0xNjBzMEKg{txO M3zFOVE3Ozl{OEKz
SKBr3 cells MmXtS5Jwf3SqIHnubIljcXSrb36gZZN{[Xl? NH7pU4VIem:5dHigbY5pcWKrdHnvckBqdiCqdX3hckBjemWjc4SgZ4Fv[2W{IGPLRpI{KGOnbHygcIlv\SC3c3nu[{BUWkJuIFnDOVA:OC5yNTFOwG0> MUmxOlM6Ojh{Mx?=
MCF7 cells NVfQSGZSTnWwY4Tpc44h[XO|YYm= NEPCclEzPCCq M1e5UWlvcGmkaYTpc44hd2ZiSIPwPVAhcW5iaIXtZY4hVUOINzDj[YxteyCjc4Pld5Nm\CCjczDI[ZIzKGyndnXsJIFnfGW{IEK0JIhzeyCkeTDX[ZN1\XKwIHLsc5QtKEmFNUC9NE4xPiEQvF2= M2XBSFE5PTdzOUK5
MRC5 cells Mn\SR5l1d3SxeHnjbZR6KGG|c3H5 M13h[2N6fG:2b4jpZ4l1gSCjZ3HpcpN1KG6xcn3hcEBtfW6pIH\pZpJw[myjc4SgUXJEPSClZXzsJIxqdmVuIFnDOVA:OSEQvF2= MX:xOlM6Ojh{Mx?=
NCI-H1299 cells NWXuVmhVTnWwY4Tpc44h[XO|YYm= NGHxWJkyOiCq NUXIO4xwWmWmdXP0bY9vKGmwIH;4fYdmdiClb37zeY1xfGmxbjDyZZRmKGmwIHj1cYFvKE6FST3INVI6QSClZXzsd{BqdmO3YnH0[YQh\m:{IEGyJIhzew>? M3fzdFI2Ozh|OUG1
NCI-H69 cells MlTwSpVv[3Srb36gZZN{[Xl? NITjc|QzPCCq NYTXVW9wSmmwZHnu[{Bi\m[rbnn0fUB1dyCKU2C5NEBqdiCqdX3hckBPS0lvSE[5JINmdGy|IHHmeIVzKDJ2IHjyd{BjgSCobIXvdoV{[2WwY3WgdI9t[XKrenH0bY9vKGG|c3H5 NHzmOFIyPzZyM{W0NC=>
NCI-N417 cells M1fqZ2Z2dmO2aX;uJIF{e2G7 NX:zUGRqOjRiaB?= MY\CbY5lcW6pIHHm[olvcXS7IITvJGhUWDlyIHnuJIh2dWGwIF7DTU1PPDF5IHPlcIx{KGGodHXyJFI1KGi{czDifUBndHWxcnXzZ4Vv[2VicH;sZZJqgmG2aX;uJIF{e2G7 Ml;5NVc3ODN3NEC=
NCI-H187 cells NUXDcIMyTnWwY4Tpc44h[XO|YYm= MmLSNlQhcA>? NEnsOGtDcW6maX7nJIFn\mmwaYT5JJRwKEiVUEmwJIlvKGi3bXHuJG5EUS2KMUi3JINmdGy|IHHmeIVzKDJ2IHjyd{BjgSCobIXvdoV{[2WwY3WgdI9t[XKrenH0bY9vKGG|c3H5 NE\X[IIyPzZyM{W0NC=>
NCI-H510 cells NFrt[mNHfW6ldHnvckBie3OjeR?= NEXZUIEzPCCq NXzoNZYySmmwZHnu[{Bi\m[rbnn0fUB1dyCKU2C5NEBqdiCqdX3hckBPS0lvSEWxNEBk\WyuczDh[pRmeiB{NDDodpMh[nliZnz1c5Jme2OnbnPlJJBwdGG{aYrheIlwdiCjc4PhfS=> NVXBUmxkOTd4MEO1OFA>
SKBR3 cells NF\F[IdHfW6ldHnvckBie3OjeR?= M3LvOVI1KGh? M3vTRWJqdmSrbnegZYZncW6rdImgeI8hUFOSOUCgbY4hcHWvYX6gV2tDWjNiY3XscJMh[W[2ZYKgNlQhcHK|IHL5JIZtfW:{ZYPj[Y5k\SCyb3zhdol7[XSrb36gZZN{[Xl? NV73UWJROTd4MEO1OFA>
NCI-H526 cells MmXiSpVv[3Srb36gZZN{[Xl? NHfvbJkyKM7:TR?= MkXtNlQhcA>? Ml33Rolv\GmwZzDh[oZqdmm2eTD0c{BJW1B7MDDpckBpfW2jbjDOR2kuUDV{NjDj[YxteyCjdDCxJJVOKGGodHXyJFI1KGi{czDifUBndHWxcnXzZ4Vv[2VicH;sZZJqgmG2aX;uJIF{e2G7 NIr4RZoyPzZyM{W0NC=>
H69AR cells MoLLSpVv[3Srb36gZZN{[Xl? M1O2U|k3KGh? NYDnbHdpUW6qaXLpeIlwdiCxZjDIV3A6OC2vZXTpZZRm\CCjboTpZZBweHSxdHnjJIFkfGm4aYT5JIlvKGi3bXHuJGg3QUGUIHPlcIx{KGG|c3Xzd4VlKGG|IHnu[JVkfGmxbjDv[kBk\WyuIHfyc5d1cCCjcoLld5Qh[XRiMUCgZYZ1\XJiOU[gbJJ{KGK7IIDyc5Bq\Gm3bTDpc4Rq\GVic4ThbY5qdmdvYnHz[YQh\myxdzDjfZRwdWW2com= MkXjNVc3ODN3NEC=
NCI-H526 cells MYDGeY5kfGmxbjDhd5NigQ>? MnfGNlQhcA>? NUnsN4RVSmmwZHnu[{Bi\m[rbnn0fUB1dyCKU2C5NEBqdiCqdX3hckBPS0lvSEWyOkBk\WyuczDh[pRmeiB{NDDodpMh[nliZnz1c5Jme2OnbnPlJJBwdGG{aYrheIlwdiCjc4PhfS=> M3Oz[FE4PjB|NUSw

... Click to View More Cell Line Experimental Data

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]

Protocol

Kinase Assay:

[1]

+ Expand

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.
Cell Research:

[1]

+ Expand
  • Cell lines: Human triple-negative breast cancers cell line MDA-MB-231
  • Concentrations: ~5μM
  • Incubation Time: 3 days
  • Method:

    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.


    (Only for Reference)
Animal Research:

[1]

+ Expand
  • Animal Models: Human triple-negative breast cancers xenografts MDA-MB-231
  • Formulation: PBS
  • Dosages: 75 mg/kg
  • Administration: i.p. on an alternate day schedule
    (Only for Reference)

Solubility (25°C)

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

* 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.

Chemical Information

Molecular Weight 512.37
Formula

C18 H21 I N6 O2 S

CAS No. 873436-91-0
Storage powder
Synonyms NSC 750424

Bio Calculators

Molarity Calculator

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

  • Mass
    Concentration
    Volume
    Molecular Weight

*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).

Dilution Calculator

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

  • C1
    V1
    C2
    V2

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

The Serial Dilution Calculator Equation

  • Serial Dilutions

  • Computed Result

  • 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):
Molecular Weight Calculator

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Total Molecular Weight: g/mol

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01581541 Completed Solid Tumors|Lymphoma National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) April 26, 2011 Phase 1
NCT01393509 Recruiting Metastatic Solid Tumor|Lymphoma|Myeloproliferative Neoplasms (MPN) Memorial Sloan Kettering Cancer Center July 2011 Phase 1
NCT01269593 Recruiting Non-Hodgkins Lymphoma|Myeloma|Active Solid Malignancy Memorial Sloan Kettering Cancer Center|Samus Therapeutics December 2010 Early Phase 1

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

  • * Indicates a Required Field

HSP (e.g. HSP90) Signaling Pathway Map

Related HSP (e.g. HSP90) Products

Tags: buy PU-H71 | PU-H71 supplier | purchase PU-H71 | PU-H71 cost | PU-H71 manufacturer | order PU-H71 | PU-H71 distributor
×
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID