PF-04929113 (SNX-5422) (Synonyms: SNX-5422) |
| Catalog No.GC11912 |
Hsp90 inhibitor,potent and selective
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 908115-27-5
Sample solution is provided at 25 µL, 10mM.
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PF-04929113 is an inhibitor of Hsp90 [1].
PF-04929113 is a water-soluble and oral pre-PF-04928473, which can be rapidly absorbed and converted into PF-04928473 after oral administration. In BT-474 xenograft mice, PF-04928473 induced the degradation of HER2 client protein. No obvious toxicity was observed when the dose reached 150mg/kg. PF-04928473 at 100mg/kg resulted in complete tumor growth inhibition and local tumor regression in some mice. In H1650 xenograft mice, PF-04928473 also showed significant anti-tumor activity. In addition, as an inhibitor of Hsp90, PF-04928473 inhibits p-ERK and p-Akt in vivo, reduces CD31+ cells and MVD, and has an effect on angiogenesis [1,2].
References:
[1] Chandarlapaty S, Sawai A, Ye Q, Scott A, Silinski M, Huang K, Fadden P, Partdrige J, Hall S, Steed P, Norton L, Rosen N, Solit DB. SNX2112, a synthetic heat shock protein 90 inhibitor, has potent antitumor activity against HER kinase-dependent cancers. Clin Cancer Res. 2008 Jan 1;14(1):240-8.
[2] Okawa Y, Hideshima T, Steed P, Vallet S, Hall S, Huang K, Rice J, Barabasz A, Foley B, Ikeda H, Raje N, Kiziltepe T, Yasui H, Enatsu S, Anderson KC. SNX-2112, a selective Hsp90 inhibitor, potently inhibits tumor cell growth, angiogenesis, and osteoclastogenesis in multiple myeloma and other hematologic tumors by abrogating signaling via Akt and ERK. Blood. 2009 Jan 22;113(4):846-55.
| Kinase experiment [1]: | |
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Affinity for Hsp90 |
Hsp90 from porcine spleen extract was isolated by affinity capture on a purine-affinity media. The Hsp90 loaded media was 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 was determined by Bradford protein assay. The resulting IC50 values were corrected for the ATP ligand concentration and presented as apparent Kd values. |
| Cell experiment [1]: | |
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Cell lines |
MCF-7, SW620, K562, SK-MEL-5 and A375 cancer cell lines |
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Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reaction Conditions |
0 ~ 300 nM; 72 or 144 hrs |
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Applications |
In a broad range of cancer cell lines (MCF-7, SW620, K562, SK-MEL-5 and A375 cells), PF-04929113 showed potent antiproliferative activity, with the IC50 values being 16, 19, 23, 25 and 51 nM, respectively. |
| Animal experiment [2]: | |
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Animal models |
Fox Chase SCID mice (6 ~ 7 weeks old) inoculated subcutaneously with 5 × 106 MM.1S cells |
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Dosage form |
20 or 40 mg/kg; p.o.; 3 times per week, for 3 weeks |
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Applications |
PF-04929113 inhibited human MM cell growth and angiogenesis in vivo. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1]. Huang KH, Veal JM, Fadden RP, Rice JW, Eaves J, Strachan JP, Barabasz AF, Foley BE, Barta TE, Ma W, Silinski MA, Hu M, Partridge JM, Scott A, DuBois LG, Freed T, Steed PM, Ommen AJ, Smith ED, Hughes PF, Woodward AR, Hanson GJ, McCall WS, Markworth CJ, Hinkley L, Jenks M, Geng L, Lewis M, Otto J, Pronk B, Verleysen K, Hall SE. Discovery of novel 2-aminobenzamide inhibitors of heat shock protein 90 as potent, selective and orally active antitumor agents. J Med Chem. 2009 Jul 23;52(14):4288-305. [2]. Okawa Y, Hideshima T, Steed P, Vallet S, Hall S, Huang K, Rice J, Barabasz A, Foley B, Ikeda H, Raje N, Kiziltepe T, Yasui H, Enatsu S, Anderson KC. SNX-2112, a selective Hsp90 inhibitor, potently inhibits tumor cell growth, angiogenesis, and osteoclastogenesis in multiple myeloma and other hematologic tumors by abrogating signaling via Akt and ERK. Blood. 2009 Jan 22;113(4):846-55. |
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| Cas No. | 908115-27-5 | SDF | |
| Synonyms | SNX-5422 | ||
| Chemical Name | [4-[2-carbamoyl-5-[6,6-dimethyl-4-oxo-3-(trifluoromethyl)-5,7-dihydroindazol-1-yl]anilino]cyclohexyl] 2-aminoacetate | ||
| Canonical 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 | ||
| Formula | C25H30F3N5O4 | M.Wt | 521.5 |
| Solubility | ≥ 23.85 mg/mL in DMSO with gentle warming | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9175 mL | 9.5877 mL | 19.1755 mL |
| 5 mM | 0.3835 mL | 1.9175 mL | 3.8351 mL |
| 10 mM | 0.1918 mL | 0.9588 mL | 1.9175 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
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.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 28 reference(s) in Google Scholar.)
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