PF-04929113 (SNX-5422)

製品コードS2656 バッチS265601

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C25H30F3N5O4
分子量 521.53 CAS No. 908115-27-5
Solubility (25°C)* 体外 DMSO 104 mg/mL (199.41 mM)
Ethanol 5 mg/mL (9.58 mM)
Water Insoluble
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 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.
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]

プロトコル(参考用のみ)

キナーゼアッセイ 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.
細胞アッセイ 細胞株 MCF-7, SW620, K562, SK-MEL-5 and A375 cancer cell lines
濃度 0-300 nM
反応時間 72 or 144 hours
実験の流れ 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.
動物実験 動物モデル 5 × 106 MM.1S cells are inoculated subcutaneously in the Fox Chase SCID mice (6-7 weeks old).
投薬量 20 or 40 mg/kg
投与方法 PF-04929113 is administered orally 3 times per week, total 3 weeks.

カスタマーフィードバック

Data from [Data independently produced by Antimicrob Agents Chemother, 2014, 58(7), 4138-44]

Data from [J Biol Chem, 2013, 288(23), 16308-20]

Data from [Data independently produced by , , Endocrine, 2016, 51(2):274-82.]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

HSP90 Inhibitor, NVP-AUY922, Improves Myelination in Vitro and Supports the Maintenance of Myelinated Axons in Neuropathic Mice. [ ACS Chem Neurosci, 2019, 10(6):2890-2902] PubMed: 31017387
The heat shock protein 90 inhibitor SNX5422 has a synergistic activity with histone deacetylase inhibitors in induction of death of anaplastic thyroid carcinoma cells. [Kim SH, et al. Endocrine, 2016, 51(2):274-82] PubMed: 26219406
Hsp90 Inhibitors as New Leads to Target Parasitic Diarrheal Diseases. [Debnath A, et al. Antimicrob Agents Chemother, 2014, 58(7):4138-44] PubMed: 24820073
Heat shock protein 90 functions to stabilize and activate the testis-specific serine/threonine kinases, a family of kinases essential for male fertility. [Jha KN J Biol Chem, 2013, 288(23):16308-20] PubMed: 23599433

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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