| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Cereblon
Cereblon (CRBN) as a ligand; neo-substrates Ikaros (IKZF1) and Aiolos (IKZF3) for ubiquitination and degradation. |
|---|---|
| ln Vitro |
One ligand is for an E3 ubiquitin ligase, and the other is for the target protein; these two ligands are joined by a linker to form PROTACs. The intracellular ubiquitin-proteasome system is utilized by PROTACs to specifically destroy target proteins[2].
Pomalidomide binds cereblon with high affinity (Kd ~1-10 uM), more potent than thalidomide or lenalidomide. The C3-NH2 spacer (3-carbon alkyl chain) provides a flexible linker. The terminal amine (as hydrochloride) enables conjugation to carboxyl-containing target ligands via amide bond formation. The compound alone induces potent degradation of Ikaros and Aiolos (DC50 ~0.1-1 uM). In PROTACs, it serves as a high-affinity cereblon recruiter. |
| Enzyme Assay |
Cereblon binding is measured by TR-FRET. Pomalidomide-C3-NH2 (0-10 uM) competes with a biotinylated pomalidomide probe. IC50 is typically 0.5-2 uM. The C3-NH2 group does not significantly reduce binding compared to pomalidomide. Binding is reversible and competitive.
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| Cell Assay |
Cells (e.g., MM.1S or HEK293) are treated with the compound alone (0.01-10 uM) for 24 hours. Ikaros and Aiolos degradation is assessed by Western blot (DC50 ~0.1-1 uM). Cell viability is measured (IC50 ~0.5-5 uM). For PROTAC evaluation, the compound is conjugated to a target warhead; the conjugate is tested at 1-1000 nM for target degradation. The intermediate alone serves as a positive control for cereblon engagement.
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| Animal Protocol |
PROTACs derived from pomalidomide-C3-NH2 are administered to xenograft mice (10-50 mg/kg, IV or IP). The intermediate alone (as a control) can also be dosed at 10-50 mg/kg to assess anti-tumor activity due to Ikaros/Aiolos degradation. Tumor growth inhibition is observed. PK parameters are measured. The C3 linker improves solubility compared to longer alkyl chains.
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| ADME/Pharmacokinetics |
Molecular weight: approximately 330 g/mol (free base) plus HCl. The C3-NH2 chain (MW ~56) provides moderate water solubility. The hydrochloride salt is stable. The compound is stored at -20degC. The glutarimide ring of pomalidomide is more stable than thalidomide (t1/2 ~4-6 hours at pH 7.4). The C3-NH2 does not affect ring stability.
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| Toxicity/Toxicokinetics |
Pomalidomide derivatives are teratogenic and potentially myelosuppressive. The C3-NH2 group does not reduce this risk. Acute toxicity: LD50 ~500-1000 mg/kg in rodents. Handle with extreme care: fume hood, double gloves. Not for human use. The compound is for research only. Avoid contact with skin.
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| References | |
| Additional Infomation |
Pomalidomide-C3-NH2 is a widely used PROTAC building block. Pomalidomide is a potent immunomodulatory drug (IMiD) approved for multiple myeloma. Compared to lenalidomide or thalidomide, pomalidomide has higher cereblon affinity, making it preferred for PROTACs requiring strong E3 ligase recruitment. The C3 spacer (propyl) is a common length for optimal ternary complex formation. This compound has no clinical approval as an intermediate.
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| Molecular Formula |
C16H19CLN4O4
|
|---|---|
| Molecular Weight |
366.799462556839
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| Exact Mass |
366.109
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| CAS # |
2154342-45-5
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| PubChem CID |
139211243
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| Appearance |
Off-white to yellow solid powder
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
25
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| Complexity |
564
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CC(=O)NC(=O)C1N2C(=O)C3=C(C2=O)C(=CC=C3)NCCCN.Cl
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| InChi Key |
MCJLKXXQNIILGB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H18N4O4.ClH/c17-7-2-8-18-10-4-1-3-9-13(10)16(24)20(15(9)23)11-5-6-12(21)19-14(11)22;/h1,3-4,11,18H,2,5-8,17H2,(H,19,21,22);1H
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| Chemical Name |
4-(3-aminopropylamino)-2-(2,6-dioxopiperidin-3-yl)isoindole-1,3-dione;hydrochloride
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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 (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 | 2.7263 mL | 13.6314 mL | 27.2628 mL | |
| 5 mM | 0.5453 mL | 2.7263 mL | 5.4526 mL | |
| 10 mM | 0.2726 mL | 1.3631 mL | 2.7263 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.
Products are for research use only; We do not sell to patients
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