| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
STAT3 9 nM (Ki)
SI-109 targets the SH2 domain of STAT3 (Signal Transducer and Activator of Transcription 3), a key transcription factor involved in cell proliferation, survival, and oncogenesis. It binds to the STAT3 SH2 domain with high affinity (Ki = 9 nM), blocking the interaction between STAT3 and its phosphorylated tyrosine motifs on activated receptors. This prevents STAT3 dimerization, nuclear translocation, and subsequent transcriptional activation of downstream target genes involved in tumor growth and survival. |
|---|---|
| ln Vitro |
In MOLM-16 cells, SI-109 has a moderate growth inhibitory effect (IC50=3 μM)[1]. SI-109 is ineffective in inhibition of STAT3 Y705 phosphorylation and in suppression of c-Myc expression at concentrations as high as 10 μM [1].
SI-109 demonstrates potent inhibition of STAT3 SH2 domain binding with a Ki of 9 nM. It effectively inhibits STAT3 transcriptional activity with an IC50 of 3 μM. In MOLM-16 cells, SI-109 exerts moderate growth inhibitory activity with an IC50 of 3 μM. Interestingly, SI-109 is ineffective in inhibiting STAT3 Y705 phosphorylation and suppressing c-Myc expression at concentrations as high as 10 μM, suggesting its mechanism of action is through direct SH2 domain binding rather than upstream kinase inhibition. |
| ln Vivo |
In vivo activity data for SI-109 are not extensively reported in the available literature. The compound's primary application has been as a tool for in vitro studies of STAT3 inhibition and as a ligand for PROTAC design. For in vivo studies, researchers typically use SI-109 derivatives or PROTAC molecules such as SD-36, which incorporate SI-109 as the STAT3-binding moiety. These downstream molecules have demonstrated antitumor efficacy in animal models. Further research is needed to characterize the direct in vivo activity of SI-109 itself.
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| Enzyme Assay |
The in vitro enzyme/receptor binding (cell-free) assay for SI-109 involves a fluorescence polarization-based competition assay to measure its binding affinity to the STAT3 SH2 domain. A fluorescently labeled phosphopeptide probe that binds to the STAT3 SH2 domain is incubated with recombinant STAT3 protein and varying concentrations of SI-109. The displacement of the probe by the compound results in a decrease in fluorescence polarization signal, from which the Ki value is calculated. Alternatively, surface plasmon resonance (SPR) can be used to directly measure the binding kinetics.
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| Cell Assay |
The in vitro cellular assay for SI-109 typically uses STAT3-dependent reporter cell lines, such as those carrying a STAT3-responsive luciferase construct. Cells are treated with varying concentrations of SI-109, and luciferase activity is measured to quantify inhibition of STAT3-mediated transcription. In MOLM-16 cells, the compound's growth inhibitory activity is assessed using standard cell viability assays such as MTT or CellTiter-Glo, with an IC50 of 3 μM reported. STAT3 Y705 phosphorylation and c-Myc expression can be evaluated by Western blot.
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| Animal Protocol |
In vivo animal studies for SI-109 are not well-documented. As a research tool primarily used for in vitro studies and PROTAC design, detailed in vivo protocols for SI-109 alone are not available. For PROTAC molecules incorporating SI-109, typical in vivo studies involve xenograft tumor models in mice, where tumor growth inhibition is assessed following administration of the compound. However, these studies reflect the properties of the PROTAC molecule rather than SI-109 itself. Researchers should consult the literature for specific protocols.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for SI-109 are not extensively reported. The compound is soluble in DMSO and has a molecular weight of 835.79. As a research tool, detailed ADME parameters including oral bioavailability, half-life, and clearance have not been characterized. The compound is primarily used for in vitro studies. If in vivo application is intended, researchers should perform their own pharmacokinetic studies to determine appropriate dosing regimens and formulations.
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| Toxicity/Toxicokinetics |
Toxicity data for SI-109 are not available in the public domain. As with most research compounds, comprehensive toxicological studies have not been performed. The compound is intended for laboratory research use only and should be handled with appropriate safety precautions. Standard laboratory safety practices, including the use of gloves, lab coats, and eye protection, should be followed. Consult the Material Safety Data Sheet for specific handling and disposal information.
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| References | |
| Additional Infomation |
((2-(((5S,8S,10aR)-3-acetyl-8-(((S)-5-amino-1-(benzhydrylamino)-1,5-dioxopentan-2-yl)carbamoyl)-6-oxodecahydropyrrolo[1,2-a][1,5]diazocin-5-yl)carbamoyl)-1H-indol-5-yl)difluoromethyl)phosphonic acid is a potent small molecule STAT3 SH2 domain inhibitor.
SI-109 is a potent STAT3 SH2 domain inhibitor (Ki = 9 nM) with antitumor activity. It inhibits STAT3 transcriptional activity with an IC50 of 3 μM. A key feature of SI-109 is its use as a STAT3-binding ligand in the design of PROTAC STAT3 degraders, such as SD-36, in combination with CRBN ligand lenalidomide. This positions SI-109 as a valuable tool for both direct inhibition and targeted degradation of STAT3. The compound is not in clinical trials and has not been approved for therapeutic use. |
| Molecular Formula |
C40H44F2N7O9P
|
|---|---|
| Molecular Weight |
835.79
|
| Exact Mass |
835.29
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| CAS # |
2429877-30-3
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| PubChem CID |
139600322
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| Appearance |
White to off-white solid powder
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| Density |
1.49±0.1 g/cm3(Predicted)
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| LogP |
1.3
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| Hydrogen Bond Donor Count |
7
|
| Hydrogen Bond Acceptor Count |
11
|
| Rotatable Bond Count |
13
|
| Heavy Atom Count |
59
|
| Complexity |
1610
|
| Defined Atom Stereocenter Count |
4
|
| SMILES |
CC(=O)N1CC[C@H]2CC[C@H](N2C(=O)[C@H](C1)NC(=O)C3=CC4=C(N3)C=CC(=C4)C(F)(F)P(=O)(O)O)C(=O)N[C@@H](CCC(=O)N)C(=O)NC(C5=CC=CC=C5)C6=CC=CC=C6
|
| InChi Key |
HBICZHLVBCLHSV-VUCLUUCHSA-N
|
| InChi Code |
InChI=1S/C40H44F2N7O9P/c1-23(50)48-19-18-28-13-16-33(38(54)45-30(15-17-34(43)51)36(52)47-35(24-8-4-2-5-9-24)25-10-6-3-7-11-25)49(28)39(55)32(22-48)46-37(53)31-21-26-20-27(12-14-29(26)44-31)40(41,42)59(56,57)58/h2-12,14,20-21,28,30,32-33,35,44H,13,15-19,22H2,1H3,(H2,43,51)(H,45,54)(H,46,53)(H,47,52)(H2,56,57,58)/t28-,30+,32+,33+/m1/s1
|
| Chemical Name |
[[2-[[(5S,8S,10aR)-3-acetyl-8-[[(2S)-5-amino-1-(benzhydrylamino)-1,5-dioxopentan-2-yl]carbamoyl]-6-oxo-1,2,4,5,8,9,10,10a-octahydropyrrolo[1,2-a][1,5]diazocin-5-yl]carbamoyl]-1H-indol-5-yl]-difluoromethyl]phosphonic acid
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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: 150 mg/mL (179.47 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 7.5 mg/mL (8.97 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 75.0 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: ≥ 7.5 mg/mL (8.97 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 75.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 7.5 mg/mL (8.97 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1965 mL | 5.9824 mL | 11.9647 mL | |
| 5 mM | 0.2393 mL | 1.1965 mL | 2.3929 mL | |
| 10 mM | 0.1196 mL | 0.5982 mL | 1.1965 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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