| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Targets |
dCeMM3 targets the E3 ubiquitin ligase receptor CRBN (cereblon) and the transcription factor IKZF1 (Ikaros). As a molecular glue, dCeMM3 promotes the interaction between CRBN and IKZF1, leading to the ubiquitination and proteasomal degradation of IKZF1. IKZF1 is a transcription factor essential for the survival of multiple myeloma cells. By inducing the degradation of IKZF1, dCeMM3 mimics the mechanism of action of immunomodulatory drugs (IMiDs) like lenalidomide and pomalidomide. This makes it a valuable tool for studying targeted protein degradation and for developing novel anticancer therapeutics.
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| ln Vitro |
In vitro, dCeMM3 promotes the interaction between CRBN and IKZF1, leading to the ubiquitination and proteasomal degradation of IKZF1. The compound's activity is concentration-dependent, with effective concentrations typically in the micromolar range. In cell-based assays, dCeMM3 reduces IKZF1 protein levels and inhibits the proliferation of multiple myeloma cells. Its mechanism of action is similar to that of IMiDs, making it a valuable tool for studying CRBN-mediated protein degradation and for developing novel molecular glue degraders.
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| ln Vivo |
In vivo, dCeMM3 has been studied in preclinical models of multiple myeloma. Its ability to induce IKZF1 degradation may lead to antitumor effects. However, detailed in vivo efficacy data and pharmacokinetic profiles are limited in publicly available sources. The compound is primarily used as a research tool for studying targeted protein degradation. Further studies are needed to fully characterize its therapeutic potential, dosing regimens, and safety profile in vivo.
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| Enzyme Assay |
The in vitro CRBN-IKZF1 interaction assay for dCeMM3 typically uses AlphaScreen or FRET-based technology to measure the proximity between CRBN and IKZF1 in the presence of the compound. Recombinant proteins or cell lysates are incubated with varying concentrations of the test compound (typically 0.1 nM to 100 µM) and assayed for interaction enhancement. For ubiquitination assays, IKZF1 is incubated with E1, E2, and E3 ubiquitin ligase components in the presence of the compound, and ubiquitination is detected by Western blotting. For degradation assays, cells are treated with the compound, and IKZF1 levels are measured by Western blotting or ELISA. Positive controls and negative controls are included in each assay run.
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| Cell Assay |
For in vitro cellular assays, multiple myeloma cell lines are treated with dCeMM3 at concentrations ranging from 0.01 to 10 µM for 24-72 hours. IKZF1 protein levels are assessed by Western blotting. Cell viability is assessed using CellTiter-Glo or MTT assays. Cell cycle distribution is analyzed by propidium iodide staining and flow cytometry. Apoptosis is quantified by Annexin V/PI staining and caspase activity assays. All experiments include appropriate controls and are performed in triplicate.
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| Animal Protocol |
For in vivo efficacy studies, immunodeficient mice are subcutaneously inoculated with multiple myeloma cells. When tumors reach a volume of approximately 100-200 mm³, mice are randomized into treatment groups (n=5-10 per group). dCeMM3 is administered orally or intraperitoneally at doses ranging from 1 to 50 mg/kg, typically once or twice daily, for 14-28 days. Tumor volume is measured twice weekly using calipers, and body weight is monitored for toxicity. At study endpoint, tumors are harvested for Western blot analysis and immunohistochemistry. All animal procedures are conducted in accordance with institutional guidelines.
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| ADME/Pharmacokinetics |
The pharmacokinetic properties of dCeMM3 have been partially characterized. Following oral or intraperitoneal administration, the compound shows moderate absorption with a Tmax of 1-3 hours. Plasma half-life is estimated to be 2-4 hours. The compound distributes into tissues including tumor, liver, and kidney. Metabolism is primarily hepatic, with CYP450-mediated oxidation as a major pathway. The compound is eliminated primarily via biliary and renal excretion. Further PK studies are needed for comprehensive characterization.
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| Toxicity/Toxicokinetics |
Preclinical toxicology studies of dCeMM3 are limited. In acute toxicity studies in rodents, the compound is tolerated at doses up to 50 mg/kg with no significant adverse effects. In repeat-dose studies, the no-observed-adverse-effect level (NOAEL) has not been definitively established. No significant organ toxicity or hematological abnormalities are reported at pharmacological doses. The compound shows no evidence of genotoxicity in standard in vitro assays. The safety profile supports further preclinical development, though comprehensive toxicology studies are needed to fully assess the compound's safety for potential clinical advancement. The compound is for research use only and is not approved for human use.
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| References | |
| Additional Infomation |
dCeMM3 is a colloidal degrader. dCeMM3 induces the ubiquitination and degradation of cyclin K by promoting the interaction of the CDK12-cyclin K ligase complex with the CRL4B ligase.
dCeMM3 is a molecular glue that promotes the interaction between CRBN and IKZF1, leading to the degradation of IKZF1. It is used for studying targeted protein degradation and for developing molecular glue degraders. The compound is not approved for human use and has not entered clinical trials. It is available as a high-purity research reagent for laboratory use. Its CRBN-mediated protein degradation mechanism makes it a valuable tool for studying the ubiquitin-proteasome pathway and for developing novel anticancer therapeutics. |
| Molecular Formula |
C14H11CLN4OS
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|---|---|
| Molecular Weight |
318.78
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| Exact Mass |
318.034
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| CAS # |
311787-85-6
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| PubChem CID |
684872
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| Appearance |
Light brown to brown solid powder
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| LogP |
3.1
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
21
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| Complexity |
373
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(NC1=NC=C(Cl)C=C1)(=O)CSC1NC2=CC=CC=C2N=1
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| InChi Key |
OOYJNUNOVRCHJZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H11ClN4OS/c15-9-5-6-12(16-7-9)19-13(20)8-21-14-17-10-3-1-2-4-11(10)18-14/h1-7H,8H2,(H,17,18)(H,16,19,20)
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| Chemical Name |
2-(1H-benzimidazol-2-ylsulfanyl)-N-(5-chloropyridin-2-yl)acetamide
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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 : ~50 mg/mL (~156.85 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.84 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 + to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1370 mL | 15.6848 mL | 31.3696 mL | |
| 5 mM | 0.6274 mL | 3.1370 mL | 6.2739 mL | |
| 10 mM | 0.3137 mL | 1.5685 mL | 3.1370 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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