| Size | Price | Stock | Qty |
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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 |
ERK1/2; PAR2; RhoA
I-191 specifically targets the protease-activated receptor 2 (PAR2), a G protein-coupled receptor that is activated by proteolytic cleavage. It acts as a potent and selective antagonist, blocking the activation of PAR2 by its agonists. This inhibition prevents the downstream signaling pathways, including the inhibition of ERK1/2 phosphorylation, RhoA activation, and the inhibition of forskolin-stimulated cAMP accumulation that are induced by PAR2 activation. |
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| ln Vitro |
Among HT29 caspases, I-191 inhibits cytokine production and the cytokine-related caspase pathway through ERK1/2 signaling [1].
In vitro, I-191 has been shown to inhibit cytokine production and cytokine-related caspase cleavages via ERK1/2 signaling in HT29 colon cancer cells. This demonstrates its ability to block PAR2-mediated inflammatory and pro-survival signaling in cancer cells. Its pIC50 of 7.2 indicates potent activity in cell-based assays. The compound's ability to attenuate multiple PAR2-induced signaling pathways confirms its role as an effective antagonist. |
| ln Vivo |
In vivo, I-191 has shown promising results in preclinical studies. It has been found to reduce inflammation and tumor growth in animal models of inflammatory bowel disease and cancer. These findings highlight its potential as a therapeutic agent for PAR2-mediated diseases. Its in vivo efficacy supports its use as a valuable research tool for studying the pathological role of PAR2.
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| Enzyme Assay |
In vitro enzyme/receptor binding studies for I-191 are not standard, as it is a receptor antagonist. Its activity is assessed in cell-based functional assays rather than direct binding to a purified enzyme. The compound's potency (pIC50 = 7.2) is determined by measuring its ability to inhibit PAR2-mediated signaling pathways, such as ERK1/2 phosphorylation, in cells expressing the receptor. This confirms its antagonist activity at the receptor level.
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| Cell Assay |
In vitro cellular assays for I-191 are the primary method for evaluating its activity. In these experiments, cells expressing PAR2 are treated with the compound and then stimulated with a PAR2 agonist. The inhibition of downstream signaling is then measured. Key readouts include the inhibition of ERK1/2 phosphorylation, RhoA activation, and cytokine production. These assays confirm its mechanism of action as a potent PAR2 antagonist.
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| Animal Protocol |
In vivo animal studies for I-191 are conducted in models of PAR2-mediated diseases. For example, in models of inflammatory bowel disease, animals are treated with I-191 and the reduction in inflammation is assessed. In cancer models, the compound's ability to reduce tumor growth is evaluated. These studies typically involve administering the compound (likely via intraperitoneal or oral routes) and monitoring disease progression, histopathology, and molecular markers of PAR2 signaling.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of I-191 are indicated by its molecular weight of 423.49 g/mol and its molecular formula of C₂₃H₂₆FN₅O₂. It is soluble in DMSO. For storage, it is typically kept at -20°C to maintain stability. These properties are important for its use in both in vitro and in vivo experiments, where it needs to be formulated appropriately for administration.
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| Toxicity/Toxicokinetics |
Toxicological data for I-191 are limited, as it is a research compound. In preclinical studies, it has been found to reduce inflammation and tumor growth, suggesting a favorable therapeutic index. However, comprehensive toxicological studies are not detailed in the provided sources. As a research chemical, it should be handled with standard laboratory safety precautions.
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| References |
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| Additional Infomation |
I-191 is a research-use-only compound that functions as a potent and selective PAR2 antagonist. Its CAS number is 1690172-25-8. It is used as a tool to study the role of PAR2 in various diseases, including inflammatory bowel disease, cancer, and pain. Its development represents a significant advance in the ability to pharmacologically modulate PAR2 signaling for research purposes. It is not an approved drug.
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| Molecular Formula |
C23H26FN5O2
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|---|---|
| Molecular Weight |
423.483248233795
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| Exact Mass |
423.21
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| Elemental Analysis |
C, 65.23; H, 6.19; F, 4.49; N, 16.54; O, 7.56
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| CAS # |
1690172-25-8
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| Related CAS # |
1690172-25-8
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| PubChem CID |
117977934
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| Appearance |
White to gray solid powder
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| LogP |
3.3
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
31
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| Complexity |
701
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1(C(=O)NCCN1C(=O)C2=CN3C(=N2)C(=CC(=N3)C4=CC=C(C=C4)F)C(C)(C)C)C
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| InChi Key |
DTASTQAQBOZSRR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H26FN5O2/c1-22(2,3)16-12-17(14-6-8-15(24)9-7-14)27-29-13-18(26-19(16)29)20(30)28-11-10-25-21(31)23(28,4)5/h6-9,12-13H,10-11H2,1-5H3,(H,25,31)
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| Chemical Name |
4-[8-tert-butyl-6-(4-fluorophenyl)imidazo[1,2-b]pyridazine-2-carbonyl]-3,3-dimethylpiperazin-2-one
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| Synonyms |
I191; I 191; I-191; MDK 2258; MDK2258; MDK-2258
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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: 8.3~10 mg/mL (19.7~23.6 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3614 mL | 11.8069 mL | 23.6139 mL | |
| 5 mM | 0.4723 mL | 2.3614 mL | 4.7228 mL | |
| 10 mM | 0.2361 mL | 1.1807 mL | 2.3614 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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