| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
| ln Vitro |
PROTAC MLKL Degrader-3 (compound C116) (1 nM-20000 nM, 0.5 μM-1 μM; 2 h-96 h) can efficiently and rapidly degrade MLKL in mouse Hepa1-6 and human HepG2 hepatocellular carcinoma cells, with DC50 values of 248.9 nM and 271.3 nM, respectively, and the maximum degradation rate of both cell lines exceeds 90% [1]. PROTAC MLKL Degrader-3 (C116) (1 μM; 4 h) can selectively degrade MLKL in mouse Hepa1-6 hepatocellular carcinoma cells without significantly affecting other proteins in the proteome [1]. PROTAC MLKL Degrader-3 (C116) (6 h) mediates the degradation of MLKL in a proteasome and CRBN-dependent manner by enhancing the ubiquitination of MLKL in mouse Hepa1-6 and human HEK293T cells [1]. PROTAC MLKL Degrader-3 (C116) (1 μM–10 μM; pretreatment for 24 hours followed by 20 hours of PA stimulation) enhanced PA-induced cell death and subsequent cytotoxicity in mouse Hepa1-6 and human HepG2 liver cancer cells, an effect dependent on cell death signaling pathways [1]. PROTAC MLKL Degrader-3 (C116) degrades MLKL in various mouse and human cancer cell lines, including colorectal cancer cells, triple-negative breast cancer cells, and lung cancer cells [1].
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| ln Vivo |
PROTAC MLKL degrader-3 (compound C116) (10 mg/kg; intraperitoneal injection; once daily) significantly reduced the level of MLKL in tumors of male C57BL/6 mice and inhibited the growth of in situ HCC tumors, and was well tolerated [1].
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| Cell Assay |
Western Blot Analysis [1]
Cell Types: Mouse Hepa1-6 hepatocellular carcinoma cells, human HepG2 hepatocellular carcinoma cells Tested Concentrations: 1 μM, 10 μM (24 hours); 1 nM-20000 nM (24 hours); 0.5 μM, 1 μM (2 hours, 4 hours, 6 hours, 12 hours, 24 hours, 48 hours, 72 hours, 96 hours) Incubation Duration: 24 hours (1 μM, 10 μM, 1 nM-20000 nM); 2 hours to 96 hours (0.5 μM, 1 μM) Experimental Results: After treatment at 1 μM concentration for 24 hours, the MLKL level in Hepa1-6 cells decreased to 9.6%, and the HepG2... The MLKL level decreased to 18.7% in cells. After 24 hours of treatment at a concentration of 10 μM, the MLKL level decreased to 2.5% in Hepa1-6 cells and 11.7% in HepG2 cells. Concentration-dependent degradation was induced, with a DC50 value of 248.9 nM in Hepa1-6 cells and 271.3 nM in HepG2 cells. The maximum degradation rate (Dₘₐₓ) was 99.3% in Hepa1-6 cells and 91.2% in HepG2 cells. At a concentration of 1 μM, MLKL was reduced by more than 90% within 2 hours, with degradation continuing for 48 hours and recovery observed within 96 hours. |
| Animal Protocol |
Animal/Disease Models:C57BL/6 (male, 5 weeks old, orthotopic liver tumor model established by surgical implantation of Hepa1-6-luc cells) [1]
Doses: 10 mg/kg Route of Administration: Intraperitoneal injection; once daily; during the study period Experimental Results: Significantly inhibited the growth of hepatocellular carcinoma (HCC) tumors, as evidenced by a decrease in total bioluminescence flux. Significantly reduced the level of MLKL in tumors of treated mice. Well tolerated, with no weight loss observed in treated mice. |
| References |
| Molecular Formula |
C49H47F4N11O8S
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|---|---|
| Molecular Weight |
1026.02
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| Appearance |
Typically exists as solids at room temperature
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| SMILES |
NC1=C(C2=C(C=N1)C3=CN(N=C3)C4CCN(CC4)C(C5CCN(C6=CC=C(C(N(C7C(NC(CC7)=O)=O)C8=O)=O)C8=C6)CC5)=O)C(C9=CC(OC(C%10=CC=C(C=C%10)F)C)=C(C=C9F)NS(=O)(C(F)F)=O)=NN2C
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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) |
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 | 0.9746 mL | 4.8732 mL | 9.7464 mL | |
| 5 mM | 0.1949 mL | 0.9746 mL | 1.9493 mL | |
| 10 mM | 0.0975 mL | 0.4873 mL | 0.9746 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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