| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg | |||
| Other Sizes |
| Targets |
The primary target is STAT6, a critical transcription factor in the signaling pathways of IL-4 and IL-13 cytokines. When STAT6 is activated via phosphorylation, it dimerizes and translocates to the nucleus to drive the expression of genes involved in Th2 cell differentiation and allergic inflammation. (S)-PM-43I also shows activity against STAT5 in some models.
|
|---|---|
| ln Vitro |
In Beas-2B immortalized human airway cells, PM-43I (0.05-5 μM; 2 hours) suppresses IL-4-stimulated STAT6 phosphorylation [1].
(S)-PM-43I inhibits IL-4-stimulated phosphorylation of STAT6 in Beas-2B immortalized human airway epithelial cells at concentrations of 0.05-5 uM for 2 hours. It potently inhibits both STAT5- and STAT6-dependent allergic airway disease in murine models and reverses pre-existing disease with an ED50 of 0.25 microg/kg, indicating high potency and efficacy. |
| ln Vivo |
PM-43I (intranasal; 5 μg per mouse; every other day; 18 days) limits activity to the lungs by intranasal administration [1].
When administered intranasally at 5 microg per mouse every other day for 18 days in a mouse model, its activity is restricted to the lung, indicating a favorable localized effect. Furthermore, it reverses pre-existing allergic airway disease in mice, a key finding for its therapeutic potential, with a minimum ED50 of 0.25 microg/kg. |
| Enzyme Assay |
While not specified, a typical biochemical assay for STAT6 is a TR-FRET-based immunoassay. Recombinant STAT6 protein is activated by a kinase (e.g., JAK1) in the presence of ATP and a peptide substrate. The inhibitor is added to the reaction mix. After incubation, a terbium-labeled anti-phospho-STAT6 antibody (pTyr641) and an acceptor dye-labeled substrate are added to generate a TR-FRET signal that is proportional to STAT6 phosphorylation.
|
| Cell Assay |
Western Blot Analysis[1]
Cell Types: Beas-2B Immortalized Human Airway Cells Tested Concentrations: 0.05, 0.1, 0.5, 1, 2.5, 5 µM Incubation Duration: 2 hrs (hours) Experimental Results: STAT6 phosphorylation levels were inhibited at 2.5 and 2.5 18% and 21% are 5 µM respectively. The standard protocol uses Beas-2B (human airway epithelial) cells or primary human CD4+ T cells polarized to Th2. Cells are pre-incubated with (S)-PM-43I for 2 hours, then stimulated with IL-4 (20 ng/mL) for 15-30 minutes to activate the JAK-STAT pathway. Cells are lysed, and the level of STAT6 phosphorylation at Tyr641 is measured by a phospho-ELISA kit or by Western blotting using a specific anti-p-STAT6 (Tyr641) antibody. |
| Animal Protocol |
Animal/Disease Models: Mice injected with ovalbumilum [1]
Doses: 5 μg per mouse Doses: Intranasal; 5 μg per mouse; each other day; 18-day Experimental Results: On peripheral spleen Cells had no effect on sensitization to ovalbumin. In a mouse model of allergic airway disease, the protocol typically involves sensitizing BALB/c mice with ovalbumin (OVA) or house dust mite extract (HDM) via intraperitoneal injection. Mice are then challenged intranasally with the same allergen. (S)-PM-43I is administered intranasally at 5 microg per mouse every other day for a total of 3-4 doses. Lung function (airway hyperresponsiveness to methacholine), inflammation, Th2 cytokine levels (IL-4, IL-5, IL-13), and STAT6 phosphorylation in lung tissue are assessed. |
| ADME/Pharmacokinetics |
Specific pharmacokinetic parameters for (S)-PM-43I are not detailed in the available literature. However, its efficacy by the intranasal route suggests it has good local retention and permeability. As a phosphatase-stable compound, it is resistant to degradation, which likely enhances its cellular activity and potency in vivo.
|
| Toxicity/Toxicokinetics |
Detailed toxicological data for (S)-PM-43I are not specified in the publicly available literature. However, as a research tool for inflammatory diseases, its safety profile is initially assessed in vivo by monitoring animal health, weight, and histological analysis of the lungs and other major organs after both acute and chronic dosing regimens, including the intranasal route of administration.
|
| References | |
| Additional Infomation |
STAT6 is a central mediator of allergic inflammation, making it a highly attractive target for diseases like asthma and atopic dermatitis. (S)-PM-43I is a potent, direct inhibitor that demonstrates oral and intranasal efficacy. As of the latest updates, this compound remains a powerful research-grade chemical tool for studying STAT6-dependent pathologies and has not yet been approved for clinical use.
|
| Molecular Formula |
C38H50F2N3O10P
|
|---|---|
| Molecular Weight |
777.79
|
| Exact Mass |
777.32
|
| CAS # |
1637532-77-4
|
| PubChem CID |
154731124
|
| Appearance |
White to off-white solid powder
|
| LogP |
6.3
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
12
|
| Rotatable Bond Count |
18
|
| Heavy Atom Count |
54
|
| Complexity |
1380
|
| Defined Atom Stereocenter Count |
1
|
| SMILES |
C(C1C=CC(=CC=1)/C(/C)=C/C(=O)N[C@H]1CCCCN(C1=O)CC(=O)N(C1C=CC=CC=1)C)(F)(F)P(=O)(OCOC(=O)C(C)(C)C)OCOC(=O)C(C)(C)C
|
| InChi Key |
MUOJHRIQZPVHNP-ZLMUDAIHSA-N
|
| InChi Code |
InChI=1S/C38H50F2N3O10P/c1-26(22-31(44)41-30-16-12-13-21-43(33(30)46)23-32(45)42(8)29-14-10-9-11-15-29)27-17-19-28(20-18-27)38(39,40)54(49,52-24-50-34(47)36(2,3)4)53-25-51-35(48)37(5,6)7/h9-11,14-15,17-20,22,30H,12-13,16,21,23-25H2,1-8H3,(H,41,44)/b26-22+/t30-/m0/s1
|
| Chemical Name |
[[difluoro-[4-[(E)-4-[[(3S)-1-[2-(N-methylanilino)-2-oxoethyl]-2-oxoazepan-3-yl]amino]-4-oxobut-2-en-2-yl]phenyl]methyl]-(2,2-dimethylpropanoyloxymethoxy)phosphoryl]oxymethyl 2,2-dimethylpropanoate
|
| 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 |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO : ~35 mg/mL (~45.00 mM)
|
|---|---|
| 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 | 1.2857 mL | 6.4285 mL | 12.8569 mL | |
| 5 mM | 0.2571 mL | 1.2857 mL | 2.5714 mL | |
| 10 mM | 0.1286 mL | 0.6428 mL | 1.2857 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
