Home Cytoskeletal Signaling HSP (HSP90) inhibitor PF-04929113 (SNX-5422)

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PF-04929113 (SNX-5422) HSP (HSP90) inhibitor

Cat.No.S2656

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

Chemical Structure

Molecular Weight: 521.53

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Chemical Information, Storage & Stability

Molecular Weight 521.53 Formula

C25H30F3N5O4

 Storage (From the date of receipt)
CAS No. 908115-27-5 Download SDF Storage of Stock Solutions

Synonyms N/A 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

Solubility

In vitro
Batch:

DMSO : 100 mg/mL ( (191.74 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 3 mg/mL

Water : Insoluble

Molarity Calculator

Mass Concentration Volume Molecular Weight

In vivo
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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.

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Mechanism of Action

Targets/IC50/Ki
HER2 [1]
37 nM
HSP90 [1]
41 nM(Kd)
In vitro
PF-04929113 (SNX-5422) is a small-molecule Hsp90 inhibitor based on the 6,7-dihydro-indazol-4-one scaffold, developed by Serenex. It converts to SNX-2122, which is the active Hsp90 inhibitor form. This compound exhibits potent effects on Her-2 stability and causes expected up-regulation of Hsp70. It also 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 (SNX-5422) 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.
In vivo
PF-04929113 (SNX-5422) inhibits human MM cell growth in vivo, and immuno-histochemical analysis shows it significantly inhibits p-ERK and p-Akt in treated mice. Meanwhile, this compound significantly decreases the percentage of CD31+ cells and MVD, consistent with an inhibitory effect on angiogenesis in vivo. A 50 mg/kg administration 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. Inhibition of tumor progression may result from a combination of decreased proliferative (reduced Ki67 and Akt expression) or increased apoptosis (increased ApopTag staining) rates. [3]
References

Applications

Methods Biomarkers Images PMID
Western blot Hsp27 / Hsp70 / AKT Grp78 / ATF4 / CHOP S2656-WB1 24411988

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

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

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