PF-04929113 (SNX-5422)

Catalog No.S2656

For research use only.

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.

PF-04929113 (SNX-5422) Chemical Structure

CAS No. 908115-27-5

Selleck's PF-04929113 (SNX-5422) has been cited by 4 Publications

3 Customer Reviews

Purity & Quality Control

Choose Selective HSP (HSP90) Inhibitors

Other HSP (HSP90) Products

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]

Assay
Methods Test Index PMID
Western blot Hsp27 / Hsp70 / AKT ; Grp78 / ATF4 / CHOP 24411988
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 (from reference)

Kinase Assay:[1]
  • 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]
  • 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.
Animal Research:[2]
  • Animal Models: 5 × 106 MM.1S cells are inoculated subcutaneously in the Fox Chase SCID mice (6-7 weeks old).
  • Dosages: 20 or 40 mg/kg
  • Administration: PF-04929113 is administered orally 3 times per week, total 3 weeks.

Solubility (25°C)

In vitro

In vivo

Add solvents to the product individually and in order
(Data is from Selleck tests instead of citations):
0.5% CMC+0.25% Tween 80
For best results, use promptly after mixing.

25 mg/mL

Chemical Information

Molecular Weight 521.53
Formula

C25H30F3N5O4

CAS No. 908115-27-5
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC1(CC2=C(C(=O)C1)C(=NN2C3=CC(=C(C=C3)C(=O)N)NC4CCC(CC4)OC(=O)CN)C(F)(F)F)C

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT02973399 Terminated Drug: SNX-5422 plus ibrutinib Cancer Esanex Inc. February 7 2017 Phase 1
NCT02914327 Withdrawn Drug: SNX-5422 plus ibrutinib Cancer Esanex Inc. February 2 2017 Phase 1
NCT00644072 Completed Drug: SNX-5422 Lymphoma|Neoplasms National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC) March 7 2008 Phase 1
NCT00647764 Completed Drug: SNX-5422 Mesylate Hsp90 inhibitor Solid Tumor Malignancy|Lymphoid Malignancy (Lymphoma and CLL)|Leukemia|Lymphoma Esanex Inc.|National Cancer Institute (NCI) March 2008 Phase 1

(data from https://clinicaltrials.gov, updated on 2022-01-17)

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

Please enter your name.
Please enter your email. Please enter a valid email address.
Please write something to us.
Tags: buy PF-04929113|PF-04929113 ic50|PF-04929113 price|PF-04929113 cost|PF-04929113 solubility dmso|PF-04929113 purchase|PF-04929113 manufacturer|PF-04929113 research buy|PF-04929113 order|PF-04929113 mouse|PF-04929113 chemical structure|PF-04929113 mw|PF-04929113 molecular weight|PF-04929113 datasheet|PF-04929113 supplier|PF-04929113 in vitro|PF-04929113 cell line|PF-04929113 concentration|PF-04929113 nmr|PF-04929113 in vivo|PF-04929113 clinical trial|PF-04929113 inhibitor|PF-04929113 Cytoskeletal Signaling inhibitor