Zelavespib (PU-H71)

For research use only.

Catalog No.S8039 Synonyms: NSC 750424

8 publications

Zelavespib (PU-H71) Chemical Structure

CAS No. 873436-91-0

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

Selleck's Zelavespib (PU-H71) has been cited by 8 publications

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. Zelavespib (PU-H71) purchased from Selleck.

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Biological Activity

Description Zelavespib (PU-H71, NSC 750424) is a potent and selective inhibitor of HSP90 with IC50 of 51 nM. Phase 1.
Features Purine-based, HSP90-selective inhibitor.
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 MXnGeY5kfGmxbjDhd5NigQ>? M3;xeGlvcGmkaYTvdpkh[WO2aY\peJkh[WejaX7zeEBJe3B7MDDpckBpfW2jbjDidoVie3RiY3HuZ4VzKE2GQT3NRk01PjhiY3XscEBtcW6nLDDFR|UxRTBwMEGwNkDPxE1? MXGxOlM6Ojh{Mx?=
SKBr3 cells M{fiXmdzd3e2aDDpcohq[mm2aX;uJIF{e2G7 MV3Hdo94fGhiaX7obYJqfGmxbjDpckBpfW2jbjDidoVie3RiY3HuZ4VzKFONQoKzJINmdGxibHnu[UB2e2mwZzDTVmItKEmFNUC9NE4xPSEQvF2= NF\KSmcyPjN7MkiyNy=>
MCF7 cells MkHISpVv[3Srb36gZZN{[Xl? MojaNlQhcA>? NH3DdZlKdmirYnn0bY9vKG:oIFjzdFkxKGmwIHj1cYFvKE2FRkegZ4VtdHNiYYPz[ZN{\WRiYYOgTIVzOiCuZY\lcEBi\nSncjCyOEBpenNiYomgW4V{fGW{bjDicI91NCCLQ{WwQVAvODZizszN MYqxPFU4OTl{OR?=
MRC5 cells M2rnXmN6fG:2b4jpZ4l1gSCjc4PhfS=> M4X6S2N6fG:2b4jpZ4l1gSCjZ3HpcpN1KG6xcn3hcEBtfW6pIH\pZpJw[myjc4SgUXJEPSClZXzsJIxqdmVuIFnDOVA:OSEQvF2= NEDMcIUyPjN7MkiyNy=>
NCI-H1299 cells NW\qVlFpTnWwY4Tpc44h[XO|YYm= NVTLdph5OTJiaB?= NV3ydGIyWmWmdXP0bY9vKGmwIH;4fYdmdiClb37zeY1xfGmxbjDyZZRmKGmwIHj1cYFvKE6FST3INVI6QSClZXzsd{BqdmO3YnH0[YQh\m:{IEGyJIhzew>? NF3EPFkzPTN6M{mxOS=>
NCI-H69 cells MmLGSpVv[3Srb36gZZN{[Xl? MWeyOEBp NV\MdI8ySmmwZHnu[{Bi\m[rbnn0fUB1dyCKU2C5NEBqdiCqdX3hckBPS0lvSE[5JINmdGy|IHHmeIVzKDJ2IHjyd{BjgSCobIXvdoV{[2WwY3WgdI9t[XKrenH0bY9vKGG|c3H5 MYGxO|YxOzV2MB?=
NCI-N417 cells MWXGeY5kfGmxbjDhd5NigQ>? MmrYNlQhcA>? NHLqdWpDcW6maX7nJIFn\mmwaYT5JJRwKEiVUEmwJIlvKGi3bXHuJG5EUS2QNEG3JINmdGy|IHHmeIVzKDJ2IHjyd{BjgSCobIXvdoV{[2WwY3WgdI9t[XKrenH0bY9vKGG|c3H5 MYWxO|YxOzV2MB?=
NCI-H187 cells M4TkWmZ2dmO2aX;uJIF{e2G7 NGPuepgzPCCq NFvpXlFDcW6maX7nJIFn\mmwaYT5JJRwKEiVUEmwJIlvKGi3bXHuJG5EUS2KMUi3JINmdGy|IHHmeIVzKDJ2IHjyd{BjgSCobIXvdoV{[2WwY3WgdI9t[XKrenH0bY9vKGG|c3H5 NHW1ZlYyPzZyM{W0NC=>
NCI-H510 cells M{nrNGZ2dmO2aX;uJIF{e2G7 MnvINlQhcA>? NF\2SHNDcW6maX7nJIFn\mmwaYT5JJRwKEiVUEmwJIlvKGi3bXHuJG5EUS2KNUGwJINmdGy|IHHmeIVzKDJ2IHjyd{BjgSCobIXvdoV{[2WwY3WgdI9t[XKrenH0bY9vKGG|c3H5 NWmxenU{OTd4MEO1OFA>
SKBR3 cells NY\C[YtETnWwY4Tpc44h[XO|YYm= MWOyOEBp NGDxcFJDcW6maX7nJIFn\mmwaYT5JJRwKEiVUEmwJIlvKGi3bXHuJHNMSlJ|IHPlcIx{KGGodHXyJFI1KGi{czDifUBndHWxcnXzZ4Vv[2VicH;sZZJqgmG2aX;uJIF{e2G7 M4T1T|E4PjB|NUSw
NCI-H526 cells Mn\MSpVv[3Srb36gZZN{[Xl? MYKxJO69VQ>? M2rZVVI1KGh? NF72dnRDcW6maX7nJIFn\mmwaYT5JJRwKEiVUEmwJIlvKGi3bXHuJG5EUS2KNUK2JINmdGy|IHH0JFEhfU1iYX\0[ZIhOjRiaILzJIJ6KG[udX;y[ZNk\W6lZTDwc4xiemm8YYTpc44h[XO|YYm= NIXhWIcyPzZyM{W0NC=>
H69AR cells NYT4fpVbTnWwY4Tpc44h[XO|YYm= NFHNTmI6PiCq MlnRTY5pcWKrdHnvckBw\iCKU2C5NE1u\WSrYYTl[EBidnSrYYDvdJRwfGmlIHHjeIl3cXS7IHnuJIh2dWGwIFi2PWFTKGOnbHzzJIF{e2W|c3XkJIF{KGmwZIXjeIlwdiCxZjDj[YxtKGe{b4f0bEBienKnc4SgZZQhOTBiYX\0[ZIhQTZiaILzJIJ6KHC{b4Dp[Il2dSCrb3Tp[IUhe3SjaX7pcocu[mG|ZXSg[oxwfyCleYTvcYV1enl? NHO2S2oyPzZyM{W0NC=>
NCI-H526 cells NEHYWohHfW6ldHnvckBie3OjeR?= MmrjNlQhcA>? MV\CbY5lcW6pIHHm[olvcXS7IITvJGhUWDlyIHnuJIh2dWGwIF7DTU1JPTJ4IHPlcIx{KGGodHXyJFI1KGi{czDifUBndHWxcnXzZ4Vv[2VicH;sZZJqgmG2aX;uJIF{e2G7 MmS0NVc3ODN3NEC=

... Click to View More Cell Line Experimental Data

Methods Test Index PMID
Western blot
AKT / c-Myc / pERK / RAF1 / EWS-FLI1 / IGF-1R / PDGFRA / c-KIT / SRC; 

PubMed: 24388362     

Immunoblot analysis of AKT, MYC, pERK, RAF‐1, EWS‐FLI1, IGF1R, PDGFRA, c‐KIT, SRC, GSK‐3β and β actin proteins in A673 and SK‐PN‐DW cell lines treated with the indicated concentrations of PU‐H71 for 24 h. Adjusted relative densities of the above proteins are shown as bar graphs below the immunoblots.

EGFR / HER3 / IGF-1R / c-Kit / Raf-1 / Akt / p90RSK / CSK / Hsp70 / Hsp90 ; 

PubMed: 19416831     

MDA-MB-468 cells were treated for 24 h with indicated concentrations of PU-H71, and protein extracts were analyzed by western blot.

Bcl-xl / p-PDK1 / p-AKT / cPARP; 

PubMed: 19416831     

MDA-MB-468 cells were treated for 24 h with vehicle and increasing concentrations of PU-H71, and protein extracts were analyzed by western blot.

LYN / SYK / BTK / AKT / MEK / ERK ; 

PubMed: 28114285     

Cells were treated with 0.5 μM PU-H71 for the indicated hours. Protein lysates were probed for BCR signaling molecules. GAPDH, loading control. 

24388362 19416831 28114285
Growth inhibition assay
Cell viability; 

PubMed: 19416831     

Representative TNBC cells were incubated with increasing concentrations of PU-H71 and growth over 72 h was assessed. y-axis values below 0% represent cell death of the starting population.

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]


Kinase Assay:


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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:


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  • 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:


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  • Animal Models: Human triple-negative breast cancers xenografts MDA-MB-231
  • 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)
Water 34 mg/mL warmed (66.35 mM)
Ethanol ''100 mg/mL warmed

* 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

C18 H21 I N6 O2 S

CAS No. 873436-91-0
Storage powder
in solvent
Synonyms NSC 750424
Smiles CC(C)NCCCN1C2=NC=NC(=C2N=C1SC3=C(C=C4C(=C3)OCO4)I)N

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Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT03935555 Recruiting Drug: PU-H71 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 Drug: PU-H71|Drug: Ruxolitinib Myelofibrosis|Primary Myelofibrosis|Post-polycythemia Vera Myelofibrosis|Post-essential Thrombocythemia Myelofibrosis Samus Therapeutics Inc. May 24 2018 Phase 1
NCT01393509 Active not recruiting Drug: PU-H71 Metastatic Solid Tumor|Lymphoma|Myeloproliferative Neoplasms (MPN) Memorial Sloan Kettering Cancer Center July 2011 Phase 1
NCT01581541 Terminated Drug: PU-H71 Solid Tumors|Lymphoma National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) April 26 2011 Phase 1

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID