- 貨號 Cat. No.
- S2656
- 規格 Size
- 5~200mg
- 品牌 Brand
- Selleckchem
Description
PF-04929113 (SNX-5422)
Catalog No.S2656
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.
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10mM/1mLIn DMSO |
USD 705 |
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5mg |
USD 340 |
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10mg |
USD 592 |
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10
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50mg |
USD 1348 |
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200mg |
USD 3238 |
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Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw
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. |
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Targets |
HSP90 |
Her-2 |
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IC50 |
41 nM (Kd) |
37 nM [1] |
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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] |
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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] |
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Features |
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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 Kd values. |
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Cell Assay: [1]
Cell lines |
MCF-7, SW620, K562, SK-MEL-5 and A375 cancer cell lines |
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Concentrations |
0-300 nM |
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Incubation Time |
72 or 144 hours |
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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. |
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Animal Study: [2]
Animal Models |
5 × 106 MM.1S cells are inoculated subcutaneously in the Fox Chase SCID mice (6-7 weeks old). |
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Dosages |
20 or 40 mg/kg |
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Administration |
PF-04929113 is administered orally 3 times per week, total 3 weeks. |
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Solubility |
0.5% CMC/0.25% Tween 80, 25 mg/mL |
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1
References
Clinical Trial Information( data from http://clinicaltrials.gov)
NCT Number |
Recruitment |
Conditions |
Sponsor
/Collaborators |
Start Date |
Phases |
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NCT01611623 |
Completed |
Cancer |
Esanex Inc. |
2012-05 |
Phase 1 |
NCT01635712 |
Withdrawn |
Cancer |
Esanex Inc. |
2012-07 |
Phase 1 |
NCT01851096 |
Recruiting |
Cancer |
Esanex Inc. |
2013-05 |
Phase 1 |
NCT01848756 |
Recruiting |
Cancer |
Esanex Inc. |
2013-08 |
Phase 1|Phase 2 |
NCT01892046 |
Recruiting |
Cancer |
Esanex Inc. |
2013-11 |
Phase 1 |
Download PF-04929113 (SNX-5422) SDF
Molecular Weight (MW) |
521.53 |
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Formula |
C25H30F3N5O4
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CAS No. |
908115-27-5 |
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Storage |
3 years -20℃Powder |
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6 months-80℃in DMSO |
Syonnyms |
N/A |
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Solubility (25°C) * |
In vitro |
DMSO |
104 mg/mL (199 mM) |
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Water |
<1 mg/mL (<1 mM) |
Ethanol |
5 mg/mL (9 mM) |
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 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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Stock Solution (1ml DMSO) |
1mM |
10mM |
20mM |
30mM |
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Mass(mg) |
0.52153 |
5.2153 |
10.4306 |
15.6459 |
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