| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| ln Vitro |
PROTAC IRAK4 degrader-14 (compound Ori-Zim-6) (250 nM; 3-24 hours) can induce time-dependent degradation of IRAK4 in the human mononuclear cell line THP-1. After treatment at a concentration of 250 nM for 12 hours, the degradation rate exceeded 90%, and after 24 hours, it was completely degraded [1]. PROTAC IRAK4 degrader-14 (250-500 nM; 12-24 hours) can induce proteasome-dependent, NCL-dependent and MDM2-dependent ubiquitination and degradation of IRAK4, and promote the assembly of the MDM2-NCL-PROTAC-IRAK4 quaternary complex in the human mononuclear cell line THP-1 [1]. PROTAC IRAK4 degrader-14 (0.01–1 μM; 24 h) inhibited LPS-induced pro-inflammatory mediator (CCL2, CXCL8, IL-6, TNF-α) mRNA expression in human monocyte cell line THP-1 in a concentration-dependent manner [1]. PROTAC IRAK4 degrader-14 (0.01–1 μM; 24 h) inhibited pro-inflammatory cytokine (TNF-α, IL-2, IFN-γ) mRNA expression in human Jurkat T cells in a concentration-dependent manner [1]. PROTAC IRAK4 degrader-14 (0.01–1 μM; 24 h) inhibited IL-1β-induced pro-inflammatory mediator (TNF-α, IL-6, CXCL8, IL-19) mRNA expression in human keratinocyte cell line HaCaT in a concentration-dependent manner [1].
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|---|---|
| ln Vivo |
PROTAC IRAK4 degrader-14 (compound Ori-Zim-6) (20 mg/kg; orally; once daily for 5 days) showed significant efficacy in an imiquimod (IMQ)-induced psoriasis mouse model, while also exhibiting good safety, including recovery of body weight and serum liver function parameters [1].
|
| Cell Assay |
Real-time quantitative PCR [1]
Cell Types: LPS-stimulated human mononuclear cell line THP-1 Tested Concentrations: 0.01, 0.1 and 1 μM Incubation Duration: 24 hours Experimental Results: It led to a concentration-dependent decrease in the mRNA levels of pro-inflammatory mediators CCL2, CXCL8, IL-6 and TNF-α. At the same concentration, the inhibitory effect on the expression of CCL2, IL-6 and TNF-α mRNA was stronger than that of the reference degrader KT-474. Real-time quantitative PCR [1] Cell Types: Human Jurkat T cells Tested Concentrations: 0.01, 0.1 and 1 μM Incubation Duration: 24 hours Experimental Results: T cell activation was inhibited by reducing the mRNA levels of TNF-α, IL-2 and IFN-γ. At the same concentration, the inhibitory effect on IFN-γ mRNA was stronger than that of KT-474. Real-time quantitative PCR[1] Cell Types: IL-1β-stimulated human keratinocytes (HaCaT cells) Tested Concentrations: 0.01-1 μM Incubation Duration: 24 hours Experimental Results: Inhibited the mRNA levels of TNF-α, IL-6, CXCL8, and IL-19. At the same concentration, the inhibitory effect on the mRNA levels of IL-6, CXCL8, and IL-19 was stronger than that of KT-474. |
| Animal Protocol |
Animal/Disease Models:BALB/c (male, 6-8 weeks old) [1]
Doses: 20 mg/kg Route of Administration: Oral; once daily for 5 consecutive days Experimental Results: Reduced total Psoriasis Area and Severity Index (PASI) score, auricular thickening, splenomegaly, and dorsal epidermal thickness. Downregulated mRNA expression of IL-1β, IL-23, lipid transporter 2 (Lcn2), and TNF-α in auricular skin tissue. Prevented imiquimod (IMQ)-induced weight loss. Significantly restored serum albumin (ALB) and alkaline phosphatase (ALP) levels. No histopathological damage was detected in major organs (heart, liver, spleen, lungs, kidneys). |
| References |
| Molecular Formula |
C59H68FN5O13
|
|---|---|
| Molecular Weight |
1074.20
|
| CAS # |
3113890-51-7
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| Appearance |
Typically exists as solids at room temperature
|
| SMILES |
O=C(O[C@H]([C@H]1CC[C@]23[H])[C@]2(C(C1=C)=O)[C@]4(O)OC[C@@]53[C@@H](O)CCC([C@@]5([H])[C@@H]4O)(C)C)CCC(N6CCC7(CCN(CC7)C(C8=CC=C(C#CC9=CN=C(OC[C@H]([C@@H]%10CC)NC([C@H]%10F)=O)C%11=CC(OC)=C(C(N)=O)C=C9%11)C=C8)=O)C6)=O
|
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 0.9309 mL | 4.6546 mL | 9.3093 mL | |
| 5 mM | 0.1862 mL | 0.9309 mL | 1.8619 mL | |
| 10 mM | 0.0931 mL | 0.4655 mL | 0.9309 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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