Name: Homo-PROTAC pVHL30 degrader 1
Brand: BOC Sciences
Rating: 5 (1 reviews)

Size

Price

Stock

Quantity

$--

In stock

Solubility

In DMSO: ≥ 150 mg/mL (127.18 mM)<br/>* "≥" means soluble, but saturation unknown.

Storage

4°C, stored under nitrogen; In solvent, -80°C, 6 months; -20°C, 1 month (stored under nitrogen)

Shipping

Room temperature in continental US; may vary elsewhere.

IUPACName

(2S,4R)-4-hydroxy-1-[(2S)-2-[[2-[2-[2-[2-[2-[2-[2-[[(2S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-2-oxoethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]acetyl]amino]-3,3-dimethylbutanoyl]-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide

Synonyms

N1,N20-Bis((S)-1-((2S,4R)-4-hydroxy-2-((4-(4-methylthiazol-5-yl)benzyl)carbamoyl)pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-yl)-3,6,9,12,15,18-hexaoxaicosanediamide; CM11; CM-11; CM 11

Boiling Point

1293.3±65.0°C at 760 Torr

Density

1.266±0.06 g/cm3

InChI Key

WGJCHHJGGFCCRS-DEYDLUNASA-N

InChI

InChI=1S/C58H82N8O14S2/c1-37-49(81-35-61-37)41-13-9-39(10-14-41)29-59-53(71)45-27-43(67)31-65(45)55(73)51(57(3,4)5)63-47(69)33-79-25-23-77-21-19-75-17-18-76-20-22-78-24-26-80-34-48(70)64-52(58(6,7)8)56(74)66-32-44(68)28-46(66)54(72)60-30-40-11-15-42(16-12-40)50-38(2)62-36-82-50/h9-16,35-36,43-46,51-52,67-68H,17-34H2,1-8H3,(H,59,71)(H,60,72)(H,63,69)(H,64,70)/t43-,44-,45+,46+,51-,52-/m1/s1

SMILES

O=C(NC(C(=O)N1CC(O)CC1C(=O)NCC=2C=CC(=CC2)C=3SC=NC3C)C(C)(C)C)COCCOCCOCCOCCOCCOCC(=O)NC(C(=O)N4CC(O)CC4C(=O)NCC=5C=CC(=CC5)C=6SC=NC6C)C(C)(C)C

Pub Chem ID

134160242

Mechanism

Target: Targets estrogen receptor alpha (ERα) for experimental targeted protein degradation studies.

Binding Site: Binds the ERα ligand-binding domain and cereblon thalidomide-binding pocket to support productive ternary complex formation.

Mechanism of Action: Homo-PROTAC pVHL30 degrader 1 is designed for use in PROTAC or targeted protein degradation experiments directed toward estrogen receptor alpha (ERα). The bifunctional molecule links a target-recognition element to cereblon, promoting proximity between the protein of interest and ubiquitination machinery. Productive ternary-complex formation can drive polyubiquitination and proteasome-dependent target depletion, allowing researchers to compare pharmacological inhibition with protein removal. It is suitable for evaluating degradation potency, kinetics, pathway selectivity, and downstream signaling consequences in engineered or disease-relevant cellular models.

Applications

• PROTAC-Mediated Targeted Degradation: Homo-PROTAC pVHL30 degrader 1 is designed for the selective degradation of proteins by leveraging the ubiquitin-proteasome system. This tool facilitates the study of protein function by enabling researchers to induce rapid and reversible protein depletion in cellular models.

• Protein-Protein Interaction Studies: This degrader aids in dissecting protein interaction networks by selectively degrading target proteins. Researchers can explore the downstream effects of protein loss, providing insights into the dynamic interactions within the cellular environment.

• Functional Genomics Research: Utilize Homo-PROTAC pVHL30 degrader 1 to investigate gene function through targeted protein degradation. This approach allows for the assessment of phenotypic changes following protein knockdown, advancing the understanding of gene regulation and expression.

• Drug Discovery and Development: The degrader serves as a powerful tool in identifying novel drug targets by demonstrating the effects of protein degradation. It supports the development of small molecules that can modulate protein levels, offering potential pathways for therapeutic intervention.

1. Homo-PROTACs: bivalent small-molecule dimerizers of the VHL E3 ubiquitin ligase to induce self-degradation.

Maniaci, C., Hughes, S.J., Testa, A., Chen, W., Lamont, D.J., Rocha, S., Alessi, D.R., Romeo, R. and Ciulli, A., 2017. Nature communications, 8(1), pp.1-14.

E3 ubiquitin ligases are key enzymes within the ubiquitin proteasome system which catalyze the ubiquitination of proteins, targeting them for proteasomal degradation. E3 ligases are gaining importance as targets to small molecules, both for direct inhibition and to be hijacked to induce the degradation of non-native neo-substrates using bivalent compounds known as PROTACs (for 'proteolysis-targeting chimeras'). We describe Homo-PROTACs as an approach to dimerize an E3 ligase to trigger its suicide-type chemical knockdown inside cells. We provide proof-of-concept of Homo-PROTACs using diverse molecules composed of two instances of a ligand for the von Hippel-Lindau (VHL) E3 ligase. The most active compound, CM11, dimerizes VHL with high avidity in vitro and induces potent, rapid and proteasome-dependent self-degradation of VHL in different cell lines, in a highly isoform-selective fashion and without triggering a hypoxic response. This approach offers a novel chemical probe for selective VHL knockdown, and demonstrates the potential for a new modality of chemical intervention on E3 ligases.

ConcentrationVolumeMass	1 mg	5 mg	10 mg
1 mM	0.85 mL	4.24 mL	8.48 mL
5 mM	0.17 mL	0.85 mL	1.7 mL
10 mM	0.08 mL	0.42 mL	0.85 mL
50 mM	0.02 mL	0.08 mL	0.17 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