| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| Other Sizes |
| Targets |
IRAK3[1]
PROTAC IRAK3 degrade-1 formic targets IRAK3 (interleukin-1 receptor-associated kinase 3), also known as IRAK-M. IRAK3 is a key regulator in immune and inflammatory responses, acting as a negative regulator of Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) signaling. The compound is a potent and specific IRAK3 degrader (IC50 = 5 nM). It binds to IRAK3 and recruits an E3 ubiquitin ligase, leading to its proteasomal degradation. |
|---|---|
| ln Vitro |
In vitro, PROTAC IRAK3 degrade-1 formic is a potent and selective IRAK3 degrader with an IC50 of 5 nM. It forms a ternary complex with IRAK3 and the E3 ubiquitin ligase, leading to the ubiquitination and subsequent degradation of IRAK3 by the proteasome. The compound is used to study the role of IRAK3 in immune and inflammatory signaling pathways. Detailed cellular data are not provided.
|
| ln Vivo |
In vivo, PROTAC IRAK3 degrade-1 formic can be used to modulate immune signaling pathways by degrading IRAK3. By inducing targeted degradation of IRAK3, this compound has the potential to be beneficial for treating conditions like autoimmune diseases, inflammation, or cancer. Specific in vivo efficacy data have not been reported. The formic salt is used for enhanced solubility.
|
| Enzyme Assay |
A cell-free binding assay for IRAK3 degradation is not typical; the mechanism requires a functional cellular degradation machinery. To assess the binding of the IRAK3 ligand to IRAK3, SPR can be used with purified IRAK3 protein. To assess CRBN binding (if the compound uses CRBN), a TR-FRET-based assay can be performed. However, the full PROTAC is typically tested in cell-based degradation assays.
|
| Cell Assay |
HEK293 or THP-1 cells expressing IRAK3 are seeded in 6-well plates. Cells are treated with PROTAC IRAK3 degrade-1 formic at varying concentrations (0.1-1000 nM) for 6-24 hours. Cells are lysed, and protein lysates are analyzed by Western blot using an anti-IRAK3 antibody. The IC50 or DC50 (concentration for 50% degradation) is calculated from densitometry data (IC50 = 5 nM). Alternatively, an ELISA-based assay can be used to quantify IRAK3 levels. Cell viability is assessed by MTT.
|
| Animal Protocol |
PROTAC IRAK3 degrade-1 formic can be studied in mouse models of inflammation or autoimmune disease. Female C57BL/6 mice (8-10 weeks, n=8-10 per group) are used in models such as LPS-induced endotoxemia or collagen-induced arthritis (CIA). The compound (1-10 mg/kg) is administered intraperitoneally or orally in a suitable vehicle (e.g., 10% DMSO + 40% PEG300 + 5% Tween 80 + 45% saline). Inflammatory cytokines (TNF-alpha, IL-6, IL-1beta) are measured by ELISA. IRAK3 degradation in immune cells is confirmed by Western blot.
|
| ADME/Pharmacokinetics |
PROTAC IRAK3 degrade-1 formic has a molecular weight of 924.10 (free base) and the molecular formula C48H65N11O8 (for the free base). It should be stored at 4degC in a sealed container, protected from moisture and light. In solvent, it is stable for 6 months at -80degC or 1 month at -20degC. The formic salt enhances solubility for in vivo and in vitro applications. Specific PK parameters have not been reported.
|
| Toxicity/Toxicokinetics |
No detailed toxicity data for PROTAC IRAK3 degrade-1 formic are available. As a research-grade PROTAC, it is used at low concentrations in vitro and in vivo. The compound is designed to degrade IRAK3, which is a negative regulator of TLR signaling. Therefore, the primary mechanism-based safety concern would be enhanced inflammation and increased susceptibility to infection. No formal toxicology studies have been published. Standard safety precautions for handling PROTAC molecules should be followed.
|
| References | |
| Additional Infomation |
PROTAC IRAK3 degrade-1 formic (Compound 23) is a research-grade PROTAC and is not approved for clinical use. It is a potent and selective degrader of IRAK3 with an IC50 of 5 nM. This compound is a valuable research tool for studying the role of IRAK3 in immune signaling, inflammation, and autoimmune diseases. It is for research use only.
|
| Molecular Formula |
C48H65N11O8
|
|---|---|
| Molecular Weight |
924.10
|
| Related CAS # |
PROTAC IRAK3 degrade-1;2712600-00-3
|
| Appearance |
Light yellow to yellow solid powder
|
| 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 and light. |
| 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 :~150 mg/mL (~162.32 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 | 1.0821 mL | 5.4107 mL | 10.8213 mL | |
| 5 mM | 0.2164 mL | 1.0821 mL | 2.1643 mL | |
| 10 mM | 0.1082 mL | 0.5411 mL | 1.0821 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
