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CC-90009 (CC90009; Eragidomide) is a novel and potent modulator of cereblon (CRBN), which is part of the cullin 4-RING E3 ubiquitin ligase complex (CRL4-CRBN E3 ubiquitin ligase; CUL4-CRBN E3 ubiquitin ligase), with potential immunomodulating and pro-apoptotic activities. Upon administration, CC-90009 specifically binds to CRBN, thereby affecting the activity of the ubiquitin E3 ligase complex. This leads to the ubiquitination of certain substrate proteins and induces the proteasome-mediated degradation of certain transcription factors, including Ikaros (IKZF1) and Aiolos (IKZF3), which are transcriptional repressors in T-cells. This reduces the levels of these transcription factors, and modulates the activity of the immune system, which may include the activation of T-lymphocytes. In addition, this downregulates the expression of other proteins, including interferon regulatory factor 4 (IRF4) and c-myc, which plays a key role in the proliferation of certain cancer cell types. CRBN, the substrate recognition component of the E3 ubiquitin ligase complex, plays a key role in the ubiquitination of certain proteins.
Physicochemical Properties
| Molecular Formula | C22H18CLF2N3O4 |
| Molecular Weight | 461.8458 |
| Exact Mass | 461.1 |
| Elemental Analysis | C, 57.21; H, 3.93; Cl, 7.68; F, 8.23; N, 9.10; O, 13.86 |
| CAS # | 1860875-51-9 |
| PubChem CID | 118647211 |
| Appearance | Off-white to light yellow solid powder |
| LogP | 2.3 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 5 |
| Heavy Atom Count | 32 |
| Complexity | 787 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | PWBHUSLMHZLGRN-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C22H18ClF2N3O4/c23-15-4-2-14(3-5-15)22(24,25)21(32)26-10-12-1-6-16-13(9-12)11-28(20(16)31)17-7-8-18(29)27-19(17)30/h1-6,9,17H,7-8,10-11H2,(H,26,32)(H,27,29,30) |
| Chemical Name | 2-(4-chlorophenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2,2-difluoroacetamide |
| Synonyms | CC-90009; CC 90009; CC90009 |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| Targets | Cereblon |
| ln Vitro | Eragidomide-induced GSPT1 depletion causes acute myeloid leukemia (AML) apoptosis to occur quickly, which lowers leukemia stem cells (LSCs) and leukemia engraftment in large-scale primary patient xenografting of 35 different AML samples. Within AML blasts and LSCs, eragidomide activity is mediated by several tiers of signaling networks and pathways[1]. |
| References |
[1]. Blood. 2021 Feb 4;137(5):661-677. [2]. J Med Chem. 2021 Feb 25;64(4):1835-1843. . [3]. https://www.cancer.gov/publications/dictionaries/cancer-drug/def/cereblon-modulator-cc-90009. |
| Additional Infomation | Eragidomide is a modulator of cereblon (CRBN), which is part of the cullin 4-RING E3 ubiquitin ligase complex (CRL4-CRBN E3 ubiquitin ligase; CUL4-CRBN E3 ubiquitin ligase), with potential immunomodulating and pro-apoptotic activities. Upon administration, eragidomide specifically binds to CRBN, thereby affecting the activity of the ubiquitin E3 ligase complex. This leads to the ubiquitination of certain substrate proteins and induces the proteasome-mediated degradation of certain transcription factors, including Ikaros (IKZF1) and Aiolos (IKZF3), which are transcriptional repressors in T-cells. This reduces the levels of these transcription factors, and modulates the activity of the immune system, which may include the activation of T-lymphocytes. In addition, this downregulates the expression of other proteins, including interferon regulatory factor 4 (IRF4) and c-myc, which plays a key role in the proliferation of certain cancer cell types. CRBN, the substrate recognition component of the E3 ubiquitin ligase complex, plays a key role in the ubiquitination of certain proteins. |
Solubility Data
| Solubility (In Vitro) | DMSO : 92~100 mg/mL ( 199.19~216.52 mM ) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.50 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 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 20.8 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. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.50 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 3: ≥ 2.08 mg/mL (4.50 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1652 mL | 10.8260 mL | 21.6521 mL | |
| 5 mM | 0.4330 mL | 2.1652 mL | 4.3304 mL | |
| 10 mM | 0.2165 mL | 1.0826 mL | 2.1652 mL |