PF-04929113 (SNX-5422)

Catalog No.S2656

PF-04929113 (SNX-5422) Chemical Structure

Molecular Weight(MW): 521.53

PF-04929113 (SNX-5422) is a potent and selective HSP90 inhibitor with Kd of 41 nM and induces Her-2 degradation with IC50 of 37 nM. Phase 1/2.

Size Price Stock Quantity  
In DMSO USD 560 In stock
USD 270 In stock
USD 470 In stock

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3 Customer Reviews

  • J Biol Chem 2013 288(23), 16308-20. PF-04929113 (SNX-5422) purchased from Selleck.

    Effect of SNX-2112 on E. histolytica morphology. Trophozoites were treated with 3 uM SNX-2112 for 48 h. (A) E. histolytica trophozoites treated with 0.5% DMSO. Arrow indicates live trophozoite. Magnification, x 10. (B) E. histolytica trophozoites treated with 3 uM SNX-2112. Treatment caused complete lysis of trophozoites (arrow). Magnification, x 10. Trophozoites were imaged under phase-contrast microscope.

    Antimicrob Agents Chemother 2014 58(7), 4138-44. PF-04929113 (SNX-5422) purchased from Selleck.

  • 8505C and CAL62 cells were treated with SNX5422 at 5 μM for 72 h, and the protein levels of hsp90, hsp70, Raf-1, GSK3b, and total and phospho-Akt were measured. All experiments were performed in triplicate. The blots are representative of independent experiments.

    Endocrine, 2016, 51(2):274-82.. PF-04929113 (SNX-5422) purchased from Selleck.

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Notes:

2. For more details, such as half maximal inhibitory concentrations (IC50s) and working concentrations of each inhibitor, please click on the link of the inhibitor of interest.
3. "+" indicates inhibitory effect. Increased inhibition is marked by a higher "+" designation.
4. Orange "√" refers to compounds which do inhibitory effects on the related isoform, but without specific value.

Biological Activity

Description PF-04929113 (SNX-5422) is a potent and selective HSP90 inhibitor with Kd of 41 nM and induces Her-2 degradation with IC50 of 37 nM. Phase 1/2.
Targets
HER2 [1] HSP90 [1]
37 nM 41 nM(Kd)
In vitro

PF-04929113 is a small-molecule Hsp90 inhibitor based on the 6,7-dihydro-indazol-4-one scaffold. PF-04929113 developed by Serenex, converts to SNX-2122, which is the active Hsp90 inhibitor form. PF-04929113 exhibits potent effects on Her-2 stability and causes expected up-regulation of Hsp70. PF-04929113 shows potent antiproliferative activity against a broad range of cancer cell types, e.g. MCF-7 (IC50=16 nM), SW620 (IC50=19 nM), K562 (IC50=23 nM), SK-MEL-5 (IC50=25 nM), and A375 (IC50=51 nM). [1]

In vivo PF-04929113 inhibits human MM cell growth in vivo, and immuno-histochemical analysis shows PF-04929113 significantly inhibits p-ERK and p-Akt in treated mice. Meanwhile, PF-04929113 treatment significantly decreases the percentage of CD31+ cells and MVD, consistent with an inhibitory effect on angiogenesis in vivo. A 50 mg/kg administration of PF-04929113 delivered 3 times per week significantly delays castrate-resistant LNCaP tumor growth and prolongs cancer specific survival. [2] Immuno-histochemical analysis indicates increased SP70 expression, and decreases Ki67, Akt, and AR expression, after treatment with PF-04929113. Inhibition of tumor progression by PF-04929113 may result from a combination of decreased proliferative (reduced Ki67 and Akt expression) or increased apoptosis (increased ApopTag staining) rates. [3]

Protocol

Kinase Assay:[1]
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Affinity for Hsp90:

Hsp90 from porcine spleen extract is isolated by affinity capture on a purine-affinity media. The Hsp90 loaded media is then challenged with PF-04929113 at a given concentration, ranging from 0.8 to 500 μM, and the amount of Hsp90 liberated at each concentration is determined by Bradford protein assay. The resulting IC50 values are corrected for the ATP ligand concentration and presented as apparent Kd values.
Cell Research:[1]
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  • Cell lines: MCF-7, SW620, K562, SK-MEL-5 and A375 cancer cell lines
  • Concentrations: 0-300 nM
  • Incubation Time: 72 or 144 hours
  • Method: All assays are done in 96-well plates. All cell lines are purchased from ATCC. Proliferation rates are measured by seeding cells into 96-well plates, followed by compound addition 24 h later. After addition of PF-04929113, cells are allowed to grow for either an additional 72 or 144 h depending on rate of growth. At harvest, media is removed and DNA content for individual wells is determined using CyQuant DNA dye. Levels of Hsp90 client proteins and phosphor-regulated proteins in A375 are measured by high content analysis (HCA) using an ArrayScan 4.5 instrument after 24 hours of treatment with PF-04929113, followed by methanol fixation. After fixation in 4% PBS-buffered formalin and permeablization with 0.1% TX-100, cells are probed with anti-Her2, antiphospho-S6 (pS6), antipERK, and anti-Hsp70 primary antibodies, followed by TRITC or FITC conjugated secondary antibodies. Nuclei are also stained with Hoechst DNA binding dye. For each well, 250-500 individual nuclei are identified along with the average staining intensity for the client and phospho-proteins for each cell. Average client staining intensities are then calculated for each well.
    (Only for Reference)
Animal Research:[2]
+ Expand
  • Animal Models: 5 × 106 MM.1S cells are inoculated subcutaneously in the Fox Chase SCID mice (6-7 weeks old).
  • Formulation: PF-04929113 is dissolved in 1% carboxy methylcellulose/0.5% Tween 80 at 10 mg/mL and stored at 4 °C for in vivo stud
  • Dosages: 20 or 40 mg/kg
  • Administration: PF-04929113 is administered orally 3 times per week, total 3 weeks.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 104 mg/mL (199.41 mM)
Ethanol 5 mg/mL (9.58 mM)
Water <1 mg/mL
In vivo 0.5% CMC+0.25% Tween 80 25 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.

Chemical Information

Molecular Weight 521.53
Formula

C25H30F3N5O4

CAS No. 908115-27-5
Storage powder
in solvent
Synonyms N/A

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02973399 Recruiting Cancer Esanex Inc. February 7, 2017 Phase 1
NCT00644072 Completed Lymphoma|Neoplasms National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) March 7, 2008 Phase 1
NCT02612285 Terminated Cancer Esanex Inc. March 2016 Phase 2
NCT02063958 Active, not recruiting Cancer Esanex Inc. February 2014 Phase 1
NCT01635712 Active, not recruiting Cancer Esanex Inc. February 2014 Phase 1
NCT01892046 Active, not recruiting Cancer Esanex Inc. November 2013 Phase 1

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID