Name: CRBN-6-5-5-VHL
Brand: BOC Sciences
Rating: 5 (1 reviews)

Size

Price

Stock

Quantity

$--

In stock

Purity

≥95%

Solubility

Soluble in DMSO

Appearance

Yellow Solid

Storage

Store at -20°C

Shipping

Room temperature in continental US; may vary elsewhere.

IUPACName

(2S,4R)-1-[(2S)-2-[5-[5-[6-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]hexoxy]pentoxy]pentanoylamino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide

Synonyms

N-[5-({5-[(6-{[2-(2,6-Dioxo-3-piperidinyl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl]amino}hexyl)oxy]pentyl}oxy)pentanoyl]-3-methyl-L-valyl-(4R)-4-hydroxy-N-[4-(4-methyl-1,3-thiazol-5-yl)benzyl]-L-prolinamide; L-Prolinamide, N-[5-[[5-[[6-[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]amino]hexyl]oxy]pentyl]oxy]-1-oxopentyl]-3-methyl-L-valyl-4-hydroxy-N-[[4-(4-methyl-5-thiazolyl)phenyl]methyl]-, (4R)-; (2S,4R)-1-((2S)-2-(5-((5-((6-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)hexyl)oxy)pentyl)oxy)pentanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide

Boiling Point

1152.7±65.0°C at 760 Torr

Density

1.265±0.06 g/cm3

InChI Key

LIMCHOLAKDUZDS-XARBDFOFSA-N

InChI

InChI=1S/C51H69N7O10S/c1-33-44(69-32-54-33)35-20-18-34(19-21-35)30-53-46(62)40-29-36(59)31-57(40)50(66)45(51(2,3)4)55-41(60)17-8-13-28-68-27-12-7-11-26-67-25-10-6-5-9-24-52-38-16-14-15-37-43(38)49(65)58(48(37)64)39-22-23-42(61)56-47(39)63/h14-16,18-21,32,36,39-40,45,52,59H,5-13,17,22-31H2,1-4H3,(H,53,62)(H,55,60)(H,56,61,63)/t36-,39?,40+,45-/m1/s1

SMILES

CC1=C(SC=N1)C2=CC=C(C=C2)CNC(=O)C3CC(CN3C(=O)C(C(C)(C)C)NC(=O)CCCCOCCCCCOCCCCCCNC4=CC=CC5=C4C(=O)N(C5=O)C6CCC(=O)NC6=O)O

Mechanism

Target: CRBN-6-5-5-VHL selectively targets cereblon for VHL-mediated proteasomal degradation.

Binding site: Its CRBN ligand binds the IMiD pocket of the cereblon substrate receptor.

Mechanism of action: CRBN-6-5-5-VHL is a VHL-recruiting cereblon degrader that links a CRBN-binding ligand to a von Hippel-Lindau ligand through a defined linker. By bringing CRBN into proximity with VHL-associated ubiquitination machinery, the compound promotes selective CRBN degradation while reportedly having little effect on the CRBN substrates IKZF1 and IKZF3. This E3-directed degrader is useful for studying cereblon abundance, E3 ligase crosstalk, dependence of CRBN-recruiting PROTACs on cereblon availability, and experimental consequences of depleting an E3 substrate receptor.

Applications

• PROTAC-Mediated Degradation: CRBN-6-5-5-VHL is designed for researchers focusing on the targeted degradation of proteins by leveraging the ubiquitin-proteasome system. By facilitating the recruitment of E3 ligase to specific target proteins, this PROTAC molecule enables precise degradation, aiding in the study of protein function and regulation.

• Targeted Protein Knockdown: Utilize CRBN-6-5-5-VHL to achieve specific protein knockdown in cellular models. This application is crucial for dissecting the role of proteins in various signaling pathways, providing insights into their contribution to cellular processes and disease mechanisms.

• E3 Ligase Recruitment: This product offers a robust tool for investigating the recruitment mechanisms of E3 ligases in targeted protein degradation. By understanding these interactions, researchers can explore novel therapeutic targets and develop strategies for selective protein modulation.

• Protein-Protein Interaction Studies: CRBN-6-5-5-VHL serves as an effective probe for studying protein-protein interactions involved in the ubiquitination pathway. This application is particularly valuable for elucidating the dynamics of protein complexes and their degradation in response to PROTAC-induced proximity.

1. PROTAC-mediated crosstalk between E3 ligases.

Steinebach, C., Kehm, H., Lindner, S., Vu, L.P., Köpff, S., Mármol, Á.L., Weiler, C., Wagner, K.G., Reichenzeller, M., Krönke, J. and Gütschow, M., 2019. Chemical Communications, 55(12), pp.1821-1824.

Small-molecule heterobifunctional degraders can effectively control protein levels and are useful research tools. We assembled proteolysis targeting chimeras (PROTACs) from a cereblon (CRBN) and a von-Hippel-Lindau (VHL) ligase ligand and demonstrated a PROTAC-induced heterodimerization of the two E3 ligases leading to unidirectional and efficient degradation of CRBN.

ConcentrationVolumeMass	1 mg	5 mg	10 mg
1 mM	1.03 mL	5.14 mL	10.29 mL
5 mM	0.21 mL	1.03 mL	2.06 mL
10 mM	0.1 mL	0.51 mL	1.03 mL
50 mM	0.02 mL	0.1 mL	0.21 mL

Stock concentration: *

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* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C₁V₁ = C₂V₂