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| Other Sizes |
| Targets |
Cereblon (CRBN), an E3 ubiquitin ligase component. Pomalidomide-C6-COOH targets CRBN by mimicking the binding of thalidomide and its analogs. The pomalidomide moiety binds to the CRBN substrate receptor, altering its substrate specificity. When conjugated to a ligand for a protein of interest (POI) via the C6-COOH linker, the resulting PROTAC molecule brings the POI into proximity with CRBN, leading to ubiquitination and proteasomal degradation of the POI. This is a key mechanism in PROTAC technology.
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| ln Vitro |
In vitro, Pomalidomide-C6-COOH itself is not evaluated for direct biological activity as it is a ligand-linker conjugate. Its activity is demonstrated when it is incorporated into a complete PROTAC molecule. The pomalidomide-based CRBN ligand has been validated in various assays for its ability to bind to CRBN. The compound serves as a building block for synthesizing PROTACs that induce degradation of target proteins. The in vitro efficacy of the final PROTAC is assessed by measuring target protein levels via Western blot in cell lines, typically showing DC50 values in the nanomolar to micromolar range.
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| ln Vivo |
In vivo activity is not applicable to Pomalidomide-C6-COOH itself as it is a synthetic intermediate for PROTAC synthesis, not a complete therapeutic agent. The in vivo efficacy would be attributed to the complete PROTAC molecule synthesized using this linker-ligand conjugate. Such PROTACs would be evaluated in animal models for target protein degradation and therapeutic efficacy. The compound itself is not administered to animals. Its role is confined to chemical synthesis as a building block. It is stored and handled based on its chemical properties.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for Pomalidomide-C6-COOH focus on its interaction with CRBN. These assays typically use surface plasmon resonance (SPR) or fluorescence polarization to measure the binding affinity (Kd) of the pomalidomide moiety to recombinant CRBN protein. Competition binding assays using fluorescently labeled thalidomide analogs can also be employed. The C6-COOH linker is not expected to interfere with CRBN binding. The compound's purity is confirmed by HPLC, and its identity is confirmed by mass spectrometry and NMR. These assays are performed in buffer solutions at physiological pH.
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| Cell Assay |
Cell-based assays are not directly performed on Pomalidomide-C6-COOH as it is a linker-ligand conjugate. However, the final PROTAC molecules synthesized from this compound are tested in cell-based degradation assays. Typically, cancer cell lines are treated with the PROTAC, and the levels of the target protein are measured by Western blot. Cell viability is assessed using MTT or CellTiter-Glo assays. The efficacy of target protein degradation (DC50) and the maximum degradation (Dmax) are determined. These assays confirm the functional activity of the PROTAC.
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| Animal Protocol |
In vivo animal experiments are not performed with Pomalidomide-C6-COOH itself. This compound is a synthetic building block used to construct PROTAC molecules. Once a complete PROTAC is synthesized, it may be tested in animal models, typically xenograft models in mice. Tumor-bearing mice are administered the PROTAC, and tumor growth inhibition, target protein degradation in tissues, and pharmacokinetics are evaluated. However, the intermediate itself is not administered to animals.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties are not applicable to Pomalidomide-C6-COOH as it is a synthetic reagent used for PROTAC synthesis. The compound is stored as a solid at -20°C and is stable for extended periods. In solvent, it is stable at -80°C for six months. It is soluble in DMSO. Its molecular weight is 401.41, and its molecular formula is C20H23N3O6. These properties are characterized to facilitate its use in chemical synthesis. No ADME studies are performed on this intermediate.
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| Toxicity/Toxicokinetics |
Toxicological data for Pomalidomide-C6-COOH are not available as it is a research chemical intermediate, not a pharmaceutical drug. Standard laboratory safety precautions for handling chemical reagents should be followed. The compound is not intended for human or animal consumption. Its specific toxicity profile has not been established. Any toxicological assessment would be performed on the final PROTAC drug candidate, not on this synthetic precursor. It is handled as a potentially hazardous material.
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| References | |
| Additional Infomation |
Pomalidomide-C6-COOH is a pomalidomide-based CRBN ligand used to recruit CRBN protein for PROTAC applications. Its molecular formula is C20H23N3O6, and its molecular weight is 401.41. It incorporates a C6 linker with a terminal carboxylic acid for conjugation to target protein ligands. It is a synthesized E3 ligase ligand-linker conjugate. It is available for research use only and is not approved for clinical or therapeutic use.
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| Molecular Formula |
C20H23N3O6
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|---|---|
| Molecular Weight |
401.41
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| Exact Mass |
401.158
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| CAS # |
2225940-50-9
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| PubChem CID |
134589631
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
713.4±60.0 °C at 760 mmHg
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| Flash Point |
385.3±32.9 °C
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| Vapour Pressure |
0.0±2.4 mmHg at 25°C
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| Index of Refraction |
1.630
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| LogP |
1
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
29
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| Complexity |
694
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C1C2C(=CC=CC=2C(N1C1C(NC(CC1)=O)=O)=O)NCCCCCCC(=O)O
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| InChi Key |
USOIUAJFCJMMOE-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H23N3O6/c24-15-10-9-14(18(27)22-15)23-19(28)12-6-5-7-13(17(12)20(23)29)21-11-4-2-1-3-8-16(25)26/h5-7,14,21H,1-4,8-11H2,(H,25,26)(H,22,24,27)
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| Chemical Name |
7-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]heptanoic acid
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 (~311.40 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 | 2.4912 mL | 12.4561 mL | 24.9122 mL | |
| 5 mM | 0.4982 mL | 2.4912 mL | 4.9824 mL | |
| 10 mM | 0.2491 mL | 1.2456 mL | 2.4912 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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