| Targets |
MG degrader 1 targets the zinc finger transcription factors IKZF1 (Ikaros) and IKZF3 (Aiolos), as well as the translation termination factors GSPT1 and GSPT2. As a molecular glue degrader, it acts by co-opting the E3 ubiquitin ligase Cereblon (CRBN). The compound induces proximity between CRBN and its neo-substrates, leading to their ubiquitination and subsequent degradation by the proteasome.
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| ln Vitro |
MG degrader 1 shows potent in vitro activity as a degrader of IKZF3, GSPT1, and GSPT2 with an EC50 value of 1.385 nM in MM.1S cells. The compound demonstrates selective degradation of its target proteins through the ubiquitin-proteasome pathway. In cellular models, MG degrader 1 effectively reduces the levels of IKZF1, IKZF3, GSPT1, and GSPT2, leading to antiproliferative effects in cancer cell lines.
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| ln Vivo |
In vivo activity of MG degrader 1 has been suggested based on its potent in vitro degradation activity and its mechanism of action as a molecular glue degrader. The compound's ability to selectively degrade oncogenic proteins positions it as a promising candidate for cancer treatments targeting specific pathways involved in tumorigenesis. However, detailed in vivo efficacy data have not been extensively reported in the available literature.
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| Enzyme Assay |
Non-cell-based binding assays for MG degrader 1 typically involve measuring the affinity of the compound for Cereblon (CRBN) and its neo-substrates. A standard protocol includes surface plasmon resonance (SPR) or fluorescence polarization (FP) using purified CRBN protein and target proteins. The compound's ability to induce ternary complex formation between CRBN and its neo-substrates can be assessed using biochemical binding assays. The degradation activity is typically evaluated in cell-based systems.
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| Cell Assay |
Cellular assays for MG degrader 1 typically involve multiple myeloma cell lines such as MM.1S cells. A representative protocol includes culturing cells in appropriate medium, treating with MG degrader 1 at various concentrations (0.001–100 nM) for 4–24 hours, and measuring target protein levels (IKZF1, IKZF3, GSPT1, GSPT2) by Western blot to determine the DC50 (half-maximal degradation concentration). Cell viability is assessed using CellTiter-Glo assays to evaluate antiproliferative effects.
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| Animal Protocol |
In vivo animal studies with MG degrader 1 are typically conducted in xenograft mouse models of multiple myeloma or other cancers dependent on IKZF1, IKZF3, GSPT1, or GSPT2. A typical protocol involves subcutaneous implantation of tumor cells in immunodeficient mice, allowing tumors to reach a certain size, administering MG degrader 1 via oral gavage or intraperitoneal injection at doses determined from pharmacokinetic studies, monitoring tumor growth and body weight, and harvesting tumors for analysis of target protein degradation by Western blot.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of MG degrader 1 have not been extensively reported in the available literature. As a molecular glue degrader with a molecular weight of 591.7 g/mol, it is expected to have reasonable oral bioavailability and tissue distribution. The compound is typically stored as a powder at -20°C for up to 3 years and is soluble in DMSO. Further PK studies are needed to fully characterize its absorption, distribution, metabolism, and excretion profile.
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| Toxicity/Toxicokinetics |
As a research compound, MG degrader 1 is not intended for human therapeutic use, and comprehensive toxicological data are limited to preclinical studies. Standard safety assessments would include cytotoxicity screening, hERG channel inhibition testing, and preliminary toxicology studies in animal models to determine maximum tolerated dose and identify potential target organs of toxicity. The compound is for research use only and not for human or veterinary use.
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| References | |
| Additional Infomation |
MG degrader 1 (Compound E14) is a novel molecular glue degrader that targets IKZF1, IKZF3, GSPT1, and GSPT2 through Cereblon-mediated degradation. The compound is referenced in the primary literature (PubMed ID: 38114468) for its potent degradation activity with an EC50 of 1.385 nM in MM.1S cells. MG degrader 1 represents a promising approach for cancer therapy by selectively degrading oncogenic proteins through the ubiquitin-proteasome pathway.
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| Molecular Formula |
C31H37N5O7
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|---|---|
| Molecular Weight |
591.65
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| Appearance |
Light yellow to yellow solid powder
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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 :~125 mg/mL (~211.27 mM; with sonication)
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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 | 1.6902 mL | 8.4509 mL | 16.9019 mL | |
| 5 mM | 0.3380 mL | 1.6902 mL | 3.3804 mL | |
| 10 mM | 0.1690 mL | 0.8451 mL | 1.6902 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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