| 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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| Other Sizes |
| Targets |
iST2-1 targets ST2 (also known as IL-1RL1), which is the receptor for interleukin-33 (IL-33). By inhibiting the ST2-IL-33 interaction, it blocks the downstream signaling cascade, which is involved in inflammatory and immune responses. This makes it a potential therapeutic for immune-related diseases.
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| ln Vitro |
iST2-1 shows inhibitory activity in biochemical assays, with IC50 values of 56.14 μM in AlphaLISA and 54.62 μM in the HEK-Blue IL-33 assay. It blocks the interaction between ST2 and IL-33, thereby inhibiting the activation of downstream signaling pathways.
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| ln Vivo |
In vivo, iST2-1 reduces plasma sST2 levels, alleviates graft-versus-host disease (GVHD), and improves survival in a murine MLL-AF9 leukemia model. It ameliorates GVHD burden while maintaining the graft-versus-leukemia (GVL) effect. This demonstrates its efficacy in a disease-relevant model.
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| Enzyme Assay |
The primary in vitro assay for iST2-1 is a binding assay that measures its ability to disrupt the ST2-IL-33 interaction. This is performed using techniques like AlphaLISA or ELISA, where the compound's ability to inhibit the binding of IL-33 to ST2 is quantified. Its IC50 is determined in this type of assay.
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| Cell Assay |
In vitro cellular assays involve using cells that express ST2 and respond to IL-33 stimulation. For example, the HEK-Blue IL-33 assay uses a cell line that produces a reporter gene upon IL-33 stimulation. iST2-1's ability to inhibit this response is measured as a functional readout of its antagonistic activity.
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| Animal Protocol |
In vivo efficacy is evaluated in a murine model of GVHD. Mice are treated with iST2-1, and its effects on GVHD progression, survival, and sST2 levels are monitored. This model demonstrates the compound's potential for treating immune-mediated diseases. Its activity is also assessed in leukemia models.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic data for iST2-1 is not extensively provided in the sources. It is described as being active in vivo, indicating it has suitable properties for systemic administration. Its molecular weight is 378.42 g/mol, and its formula is C22H22N2O4.
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| Toxicity/Toxicokinetics |
Toxicological data for iST2-1 is not detailed in the provided sources. As a research compound, it is not intended for human use. Standard preclinical safety studies would be required for its development as a therapeutic. It is supplied for research purposes only.
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| References |
Ramadan AM, Daguindau E, Rech JC, Chinnaswamy K, Zhang J, Hura GL, Griesenauer B, Bolten Z, Robida A, Larsen M, Stuckey JA, Yang CY, Paczesny S. From proteomics to discovery of first-in-class ST2 inhibitors active in vivo. JCI Insight. 2018 Jul 25;3(14). pii: 99208. doi: 10.1172/jci.insight.99208. [Epub ahead of print] PubMed PMID: 30046004; PubMed Central PMCID: PMC6124397.
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| Additional Infomation |
iST2-1 is a first-in-class ST2 inhibitor. It represents a novel approach to modulating the IL-33/ST2 pathway, which is a key driver of inflammation in various diseases, including GVHD and asthma. Its ability to maintain the GVL effect while reducing GVHD is a particularly promising feature.
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| Molecular Formula |
C22H22N2O4
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|---|---|
| Molecular Weight |
378.43
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| Exact Mass |
378.157
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| CAS # |
1019158-02-1
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| Related CAS # |
1019158-02-1;
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| PubChem CID |
46266483
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| Appearance |
Yellow to brown liquid (Density: 1.235±0.06 g/cm3)
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
500.5±50.0 °C at 760 mmHg
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| Flash Point |
256.5±30.1 °C
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| Vapour Pressure |
0.0±1.3 mmHg at 25°C
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| Index of Refraction |
1.607
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| LogP |
4.04
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
28
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| Complexity |
517
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O1C(C2C=CC=CC=2[N+](=O)[O-])=CC=C1CN1CCCC1C1C=CC(=CC=1)OC
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| InChi Key |
RBVNERPDMZVXIP-UHFFFAOYSA-N InChi Code
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| InChi Code |
InChI=1S/C22H22N2O4/c1-27-17-10-8-16(9-11-17)20-7-4-14-23(20)15-18-12-13-22(28-18)19-5-2-3-6-21(19)24(25)26/h2-3,5-6,8-13,20H,4,7,14-15H2,1H3
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| Chemical Name |
2-(4-Methoxyphenyl)-1-((5-(2-nitrophenyl)furan-2-yl)methyl)pyrrolidine
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| Synonyms |
i-ST2-1 iST2 1 iST2-1
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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 (~264.3 mM; with ultrasonication)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (13.21 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 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 DMSO stock solution (50.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6425 mL | 13.2125 mL | 26.4250 mL | |
| 5 mM | 0.5285 mL | 2.6425 mL | 5.2850 mL | |
| 10 mM | 0.2642 mL | 1.3212 mL | 2.6425 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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