PF-04929113 (SNX-5422)

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PF-04929113 (SNX-5422) is available in the following compound libraries:

Chemical Library (96-well) Inhibitor Library (96-well) Pfizer Licensed Library

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Dr. Antonino Maria Sparta demonstrates a breakthrough in leukemia research by utilizing two inhibitors produced by Selleck Chemicals.

Cat.No.	Product Name	Solubility (25°C)
S1141	17-AAG (Tanespimycin)	<1 mg/mL	117 mg/mL	5 mg/mL
S1069	AUY922 (NVP-AUY922)	<1 mg/mL	93 mg/mL	93 mg/mL
S1052	Elesclomol	<1 mg/mL	80 mg/mL	<1 mg/mL
S1159	Ganetespib (STA-9090)	<1 mg/mL	40 mg/mL	9 mg/mL
S1142	17-DMAG HCl (Alvespimycin)	<1 mg/mL	131 mg/mL	<1 mg/mL
S2713	Geldanamycin	<1 mg/mL	112 mg/mL	<1 mg/mL
S1163	AT13387	<1 mg/mL	25 mg/mL	<1 mg/mL
S1498	NVP-BEP800	<1 mg/mL	<1 mg/mL	15 mg/mL
S1175	BIIB021	<1 mg/mL	64 mg/mL	2 mg/mL
S2639	SNX-2112	<1 mg/mL	93 mg/mL	1 mg/mL
S2656	PF-04929113 (SNX-5422)	<1 mg/mL	104 mg/mL	5 mg/mL
S2685	KW-2478	<1 mg/mL	115 mg/mL	3 mg/mL

Product Description

Biological Activity Protocol Chemical Information Tech Support & FAQs

Biological Activity

Description	PF-04929113 (SNX-5422) is a potent and selective HSP90 inhibitor with K_d of 41 nM and also inhibits Her-2 degradation with IC50 of 37 nM.
Targets	HSP90	Her-2
IC50	41 nM (K_d)	37 nM ^[1]
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]
Clinical Trials	PF-04929113 is currently under the Phase I clinical trial for the safety and pharmacology study in subjects with refractory solid tumor malignancies.
Features

Protocol(Only for 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 K_d values.

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 K_d values.

Cell Assay: ^[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 Study: ^[2]

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 study.
Dosages	20 or 40 mg/kg
Administration	PF-04929113 is administered orally 3 times per week, total 3 weeks.

1

References

Chemical Information

Download PF-04929113 (SNX-5422) SDF

Molecular Weight (MW)	521.53
Formula	C₂₅H₃₀F₃N₅O₄
CAS No.	908115-27-5, 1173111-67-5 (methanesulfonate)
Synonyms	N/A

Solubility (25°C) DMSO 104 mg/mL Water <1 mg/mL Ethanol 5 mg/mL
Storage	2 years -20°CPowder
	2 weeks4°Cin DMSO
	6 months-80°Cin DMSO

Chemical Name	(1r,4r)-4-(2-carbamoyl-5-(6,6-dimethyl-4-oxo-3-(trifluoromethyl)-4,5,6,7-tetrahydroindazol-1-yl)phenylamino)cyclohexyl 2-aminoacetate

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Tech Support & FAQs

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:3Monday–Friday 9:00 AM–5:00 PM (Central Time)

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Validation & Quality Control

Quality Control & MSDS

Related Compound Libraries

PF-04929113 (SNX-5422) is available in the following compound libraries:

Product Information

Compare HSP (e.g. HSP90) Inhibitors

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Product Description

Biological Activity

Protocol(Only for Reference)

Kinase Assay: ^[1]

Cell Assay: ^[1]

Animal Study: ^[2]

References

Chemical Information

Research Area

Tech Support & FAQs

If you have any other enquiries, please leave a message.

Related HSP (e.g. HSP90) Inhibitors

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Cat.No.	Product Name	Solubility (25°C)
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S1141	17-AAG (Tanespimycin)	<1 mg/mL	117 mg/mL	5 mg/mL
S1069	AUY922 (NVP-AUY922)	<1 mg/mL	93 mg/mL	93 mg/mL
S1052	Elesclomol	<1 mg/mL	80 mg/mL	<1 mg/mL
S1159	Ganetespib (STA-9090)	<1 mg/mL	40 mg/mL	9 mg/mL
S1142	17-DMAG HCl (Alvespimycin)	<1 mg/mL	131 mg/mL	<1 mg/mL
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S1163	AT13387	<1 mg/mL	25 mg/mL	<1 mg/mL
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S1175	BIIB021	<1 mg/mL	64 mg/mL	2 mg/mL
S2639	SNX-2112	<1 mg/mL	93 mg/mL	1 mg/mL
S2656	PF-04929113 (SNX-5422)	<1 mg/mL	104 mg/mL	5 mg/mL
S2685	KW-2478	<1 mg/mL	115 mg/mL	3 mg/mL

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Product Categories

PF-04929113 (SNX-5422)

Validation & Quality Control

Quality Control & MSDS

Related Compound Libraries

PF-04929113 (SNX-5422) is available in the following compound libraries:

Product Information

Compare HSP (e.g. HSP90) Inhibitors

Research Area

Product Description

Biological Activity

Protocol(Only for Reference)

Kinase Assay: [1]

Cell Assay: [1]

Animal Study: [2]

References

Chemical Information

Research Area

Tech Support & FAQs

If you have any other enquiries, please leave a message.

Related HSP (e.g. HSP90) Inhibitors

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Kinase Assay: ^[1]

Cell Assay: ^[1]

Animal Study: ^[2]