| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| Targets |
HS-27 targets heat shock protein 90 (Hsp90), a molecular chaperone that is overexpressed in many cancer cells and is essential for the stability and function of numerous oncogenic client proteins. The SNX-5422 moiety binds to the ATP-binding pocket of Hsp90, inhibiting its chaperone activity and leading to the degradation of client proteins such as HER2, AKT, and RAF. The PEG linker provides flexibility and spacing between the inhibitor and the FITC moiety. The FITC moiety allows for fluorescence-based detection and imaging of Hsp90-expressing cells.
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| ln Vitro |
HS-27 preferentially binds to Hsp90 expressed on the surface of breast cancer cells before being internalized, labeling all receptor subtypes in breast cancer but not in normal cells. Tumor tissue exhibits stronger HS-27 fluorescence than non-tumor tissue [1].
In vitro, HS-27 has been shown to label all receptor subtypes of breast cancer cells, but not normal cells, due to the specific binding to Hsp90 expressed on the surface of cancer cells. After binding, HS-27 is internalized into the cancer cells. The compound demonstrates increased fluorescence in tumor tissue compared to non-tumor tissue, confirming its specificity for Hsp90-expressing cancer cells. The inhibition of Hsp90 by HS-27 leads to the degradation of client proteins and induces apoptosis in cancer cells. These in vitro findings support the use of HS-27 as a theranostic agent. |
| ln Vivo |
In vivo, HS-27 has potential use in a "see-and-treat" paradigm in breast cancer. The compound's fluorescence allows for the visualization of Hsp90-expressing tumors in animal models. The Hsp90 inhibitory activity of SNX-5422 provides therapeutic efficacy by degrading oncogenic client proteins and inhibiting tumor growth. The PEG linker improves the solubility and pharmacokinetic properties of the conjugate. Studies have demonstrated increased fluorescence in tumor tissue compared to non-tumor tissue, confirming the tumor-specific accumulation of HS-27.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for HS-27 involve measuring its binding affinity to Hsp90. The assay is typically performed using surface plasmon resonance (SPR) or fluorescence polarization. The binding of the SNX-5422 moiety to the ATP-binding pocket of Hsp90 is measured, and the KD value is calculated. The specificity of binding is confirmed by competition experiments with excess SNX-5422 or other Hsp90 inhibitors. The fluorescence of the FITC moiety can be used to monitor the binding of the compound to Hsp90 in real-time.
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| Cell Assay |
In vitro cellular experiments for HS-27 are performed using breast cancer cell lines. Cells are treated with varying concentrations of HS-27, and the fluorescence is measured using flow cytometry or fluorescence microscopy to assess binding and internalization. The effect of HS-27 on Hsp90 client protein levels (e.g., HER2, AKT) is assessed by Western blot. Cell viability is measured using an MTT or CellTiter-Glo assay to determine the antiproliferative effect of the compound. The specificity of HS-27 for cancer cells over normal cells is confirmed by comparing its effects on different cell lines.
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| Animal Protocol |
In vivo animal studies for HS-27 are conducted using mouse models of breast cancer. Tumor-bearing mice are administered HS-27 via intravenous injection. The fluorescence of the compound in the tumor tissue is monitored using in vivo imaging systems. The antitumor efficacy of HS-27 is evaluated by measuring tumor growth inhibition. At the end of the study, tumors and major organs are collected for histopathological analysis and to measure the levels of Hsp90 client proteins.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of HS-27 are influenced by the PEG linker, which improves the solubility and circulation time of the conjugate. The compound is expected to have a moderate half-life, allowing for sufficient accumulation in tumor tissue. The FITC moiety allows for the tracking of the compound's distribution in vivo. The compound is metabolized in the liver, and its metabolites are excreted via the biliary and renal routes. The pharmacokinetic profile of HS-27 supports its use in imaging and therapeutic studies.
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| Toxicity/Toxicokinetics |
The toxicity profile of HS-27 has not been extensively characterized in the literature. As an Hsp90 inhibitor, it is expected to have a similar safety profile to other Hsp90 inhibitors, with potential adverse effects including hepatotoxicity, gastrointestinal disturbances, and ocular toxicity. The specificity of the compound for cancer cells over normal cells may reduce off-target effects. Standard toxicology studies would be required to fully characterize its safety profile.
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| References | |
| Additional Infomation |
HS-27 is a fluorescently tethered Hsp90 inhibitor that enables a "see-and-treat" paradigm in breast cancer. It consists of the Hsp90 inhibitor SNX-5422 linked to FITC via a PEG linker. The compound specifically labels Hsp90 expressed on the surface of breast cancer cells, allowing for both imaging and therapy. HS-27 demonstrates increased fluorescence in tumor tissue compared to non-tumor tissue, confirming its tumor-specific accumulation. This theranostic agent represents a promising approach for the diagnosis and treatment of Hsp90-expressing cancers.
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| Molecular Formula |
C52H60N6O12S
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|---|---|
| Molecular Weight |
993.130812644959
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| Exact Mass |
992.398
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| CAS # |
1562024-11-6
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| PubChem CID |
72943314
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| Appearance |
Yellow to orange solid powder
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| LogP |
5.4
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
15
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| Rotatable Bond Count |
24
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| Heavy Atom Count |
71
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| Complexity |
1740
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S=C(NCCCOCCOCCOCCOCCOCCCNC1=C(C(N)=O)C=CC(=C1)N1C2=C(C(C)=N1)C(CC(C)(C)C2)=O)NC1C=CC2=C(C=1)C(=O)OC12C2C=CC(=CC=2OC2C=C(C=CC1=2)O)O
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| InChi Key |
QUGHMMYGFASWKI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C52H60N6O12S/c1-32-47-43(30-51(2,3)31-44(47)61)58(57-32)34-7-10-37(48(53)62)42(27-34)54-14-4-16-64-18-20-66-22-24-68-25-23-67-21-19-65-17-5-15-55-50(71)56-33-6-11-39-38(26-33)49(63)70-52(39)40-12-8-35(59)28-45(40)69-46-29-36(60)9-13-41(46)52/h6-13,26-29,54,59-60H,4-5,14-25,30-31H2,1-3H3,(H2,53,62)(H2,55,56,71)
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| Chemical Name |
2-[3-[2-[2-[2-[2-[3-[(3',6'-dihydroxy-3-oxospiro[2-benzofuran-1,9'-xanthene]-5-yl)carbamothioylamino]propoxy]ethoxy]ethoxy]ethoxy]ethoxy]propylamino]-4-(3,6,6-trimethyl-4-oxo-5,7-dihydroindazol-1-yl)benzamide
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| Synonyms |
HS27; HS 27
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~100.69 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (2.52 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (2.52 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. View More
Solubility in Formulation 3: 2.08 mg/mL (2.09 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.0069 mL | 5.0346 mL | 10.0692 mL | |
| 5 mM | 0.2014 mL | 1.0069 mL | 2.0138 mL | |
| 10 mM | 0.1007 mL | 0.5035 mL | 1.0069 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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