Home Cytoskeletal Signaling HSP (HSP90) inhibitor PF-04929113 (SNX-5422) For research use only.

PF-04929113 (SNX-5422)

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

PF-04929113 (SNX-5422) Chemical Structure

CAS No. 908115-27-5

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PF-04929113 (SNX-5422) Related Products

Signaling Pathway

HSP (HSP90) Signaling Pathways

HSP (HSP90) Signaling Pathway

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
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]
Kinase Assay 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 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.
Experimental Result Images Methods Biomarkers Images PMID
Western blot Hsp27 / Hsp70 / AKT Grp78 / ATF4 / CHOP 24411988
In Vivo
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]
Animal Research 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.
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02973399 Terminated
Cancer
Esanex Inc.
 February 7 2017 Phase 1
NCT02914327 Withdrawn
Cancer
Esanex Inc.
 February 2 2017 Phase 1
NCT00644072 Completed
Lymphoma|Neoplasms
National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC)
 March 7 2008 Phase 1
NCT00647764 Completed
Solid Tumor Malignancy|Lymphoid Malignancy (Lymphoma and CLL)|Leukemia|Lymphoma
Esanex Inc.|National Cancer Institute (NCI)
 March 2008 Phase 1

Chemical Information & Solubility

Molecular Weight 521.53 Formula

C25H30F3N5O4
CAS No. 908115-27-5 SDF Download PF-04929113 (SNX-5422) SDF
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
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 104 mg/mL ( (199.41 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 5 mg/mL

Water : Insoluble


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In vivo
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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

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