CRBN-6-5-5-VHL
Based on 1 publication(s) in Google Scholar
CRBN-6-5-5-VHL is a potent and selective VHL E3 ligand-based Cereblon (CRBN) PROTAC degrader with a DC50 value of 1.5 nM. CRBN-6-5-5-VHL forms a heterotrimeric complex with CRBN and VHL E3 ligase, thereby promoting CRBN ubiquitination and proteasomal degradation without inducing VHL degradation. CRBN-6-5-5-VHL protects myeloma from the toxic effects of IMiDs. CRBN-6-5-5-VHL can be used in the research of multiple myeloma.
(Pink: Cereblon ligand (HY-10984); Blue: VHL ligand (HY-125845); Black: linker (HY-403544)).
For research use only. We do not sell to patients.
- Purity: 98.97%
- CAS No.: 2362575-45-7
- Formula: C51H69N7O10S
- Molecular Weight:972.20
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Storage:
-20°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Purity & Documentation
- References
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Help & FAQs
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Publications Citing Use of MedChemExpress (MCE) CRBN-6-5-5-VHL
MoreAll PROTACs Isoforms
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Biological Activity
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Cereblon 1.5 nM (DC50) |
VHL |
CRBN-6-5-5-VHL (0.01-1 μM; 24-96 h) efficiently and selectively degrades CRBN in MM1S multiple myeloma cells via the ubiquitin-proteasome pathway, with a DC50 of 1.5 nM. It does not affect VHL levels or induce the degradation of novel substrates, while also protecting cells from IMiD toxicity[1].
CRBN-6-5-5-VHL (100 nM; 96 h) shows no toxicity to MM1S multiple myeloma cells, and pretreatment with 100 nM for 3 h rescues cells from Pomalidomide (HY-10984)- and Lenalidomide (HY-A0003)-induced cell death[1].
CRBN-6-5-5-VHL (1 μM; 6 h) blocks the cereblon-dependent effects of Lenalidomide and Pomalidomide, including downregulation of CCL5, in myeloma-derived cell lines KMS-12-BM and KMS-28-PE[2].
CRBN-6-5-5-VHL selectively degrades CRBN in MM1S multiple myeloma cells, but does not degrade VHL or the novel CRBN substrates IKZF1 and IKZF3, and exhibits superior CRBN-degrading efficacy compared to its homologous PROTAC CC15a[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MM1S multiple myeloma cells
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Concentration:0.01 μM-1 μM
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Incubation Time:24 h; 3 h pre-treatment followed by 96 h combined treatment; 48 h
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Result:Induced complete degradation of CRBN at 1 μM for 24 h.
Showed no changes in VHL protein levels even at concentrations up to 10 μM.
Had a DC50 value of 1.5 nM for CRBN degradation.
Reduced remaining CRBN levels to less than 10% at 100 nM for 24 h.
Showed negligible effect on degradation of the neo-substrates IKZF1 and IKZF3 at 100 nM for 24 h.
Had CRBN degradation abrogated by co-treatment with excess pomalidomide or VH298.
Had CRBN degradation prevented by incubation with MG132 or MLN4924.
Maintained CRBN levels below 50% for more than 48 h after a single 100 nM treatment.
Protected MM1S cells from pomalidomide- and lenalidomide-induced toxicity by preventing IKZF1 and IKZF3 degradation after 100 nM pre-treatment for 3 h followed by 96 h combined treatment.
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Cell Line:MM1S multiple myeloma cells
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Concentration:100 nM
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Incubation Time:96 h; 3 h pre-treatment followed by 96 h combined treatment
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Result:Did not reduce MM1S cell viability relative to DMSO controls after single treatment with 100 nM for 96 h.
Significantly increased cell viability compared to treatment with pomalidomide or lenalidomide alone after pre-treatment with 100 nM for 3 h followed by combined treatment with 1 μM pomalidomide or lenalidomide for 96 h.
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Cell Line:KMS-12-BM, KMS-28-PE
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Concentration:1 μM (pretreatment)
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Incubation Time:6 h (pretreatment); 48 h (lenalidomide/pomalidomide treatment)
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Result:Effectively degraded CRBN in KMS-12-BM and KMS-28-PE cells.
Blocked lenalidomide- or pomalidomide-induced degradation of IKZF1 and IKZF3.
Chemical Information
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CAS No. 2362575-45-7
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Appearance Solid
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Molecular Weight 972.20
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Formula C51H69N7O10S
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Color Light yellow to yellow
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SMILES
O=C(N1C(CCC2=O)C(N2)=O)C(C(C1=O)=CC=C3)=C3NCCCCCCOCCCCCOCCCCC(N[C@@H](C(C)(C)C)C(N(C[C@@H]4O)[C@@H](C4)C(NCC5=CC=C(C(SC=N6)=C6C)C=C5)=O)=O)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
-20°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Publications (1)
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Journal Impact Factor
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Most Recent
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J Med Chem
Leveraging Targeted Protein Degradation for G Protein-Coupled Receptors: The Development of CCR2 Molecular Degraders. [Abstract]2025 Dec 25;68(24):26525-26546. PMID: 41381043
Solvent & Solubility
DMSO : 113.33 mg/mL (116.57 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Purity & Documentation
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Data Sheet (278 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
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Handling Instructions (2659 KB)
References
[1]. Steinebach C, et al. PROTAC-mediated crosstalk between E3 ligases. Chemical communications (Cambridge, England). 2019 Feb 05;55(12):1821-1824. [Content Brief]
[2]. Kuwahara-Ota S, et al. Lenalidomide and pomalidomide potently interfere with induction of myeloid-derived suppressor cells in multiple myeloma. British journal of haematology. 2020 Dec;191(5):784-795. [Content Brief]
[3]. Konstantinidou M, et al. PROTACs- a game-changing technology. Expert opinion on drug discovery. 2019 Dec;14(12):1255-1268. [Content Brief]
[4]. Essa K, et al. Leveraging Targeted Protein Degradation for G Protein-Coupled Receptors: The Development of CCR2 Molecular Degraders. Journal of medicinal chemistry. 2025 Dec 25;68(24):26525-26546. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.0286 mL | 5.1430 mL | 10.2859 mL | 25.7149 mL |
| 5 mM | 0.2057 mL | 1.0286 mL | 2.0572 mL | 5.1430 mL | |
| 10 mM | 0.1029 mL | 0.5143 mL | 1.0286 mL | 2.5715 mL | |
| 15 mM | 0.0686 mL | 0.3429 mL | 0.6857 mL | 1.7143 mL | |
| 20 mM | 0.0514 mL | 0.2571 mL | 0.5143 mL | 1.2857 mL | |
| 25 mM | 0.0411 mL | 0.2057 mL | 0.4114 mL | 1.0286 mL | |
| 30 mM | 0.0343 mL | 0.1714 mL | 0.3429 mL | 0.8572 mL | |
| 40 mM | 0.0257 mL | 0.1286 mL | 0.2571 mL | 0.6429 mL | |
| 50 mM | 0.0206 mL | 0.1029 mL | 0.2057 mL | 0.5143 mL | |
| 60 mM | 0.0171 mL | 0.0857 mL | 0.1714 mL | 0.4286 mL | |
| 80 mM | 0.0129 mL | 0.0643 mL | 0.1286 mL | 0.3214 mL | |
| 100 mM | 0.0103 mL | 0.0514 mL | 0.1029 mL | 0.2571 mL |
CRBN-6-5-5-VHL Related Classifications
HY-136262 Related Classifications
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