Name: PROTAC_ERRα
Brand: BOC Sciences
Rating: 5 (1 reviews)

Size

Price

Stock

Quantity

$--

In stock

ShelfLife

2 years

IUPACName

(2S,4R)-1-[(2S)-2-[3-[2-[(5Z)-5-[[4-[4-cyano-2-(trifluoromethyl)phenoxy]-3-methoxyphenyl]methylidene]-2,4-dioxo-1,3-thiazolidin-3-yl]ethoxy]propanoylamino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide

Synonyms

(2S,4R)-1-((S)-2-(3-(2-(5-((Z)-4-(4-cyano-2-(trifluoromethyl)phenoxy)-3-methoxybenzylidene)-2,4-dioxothiazolidin-3-yl)ethoxy)propanamido)-3,3-dimethylbutanoyl)-4-hydroxy-N-(4-(4-methylthiazol-5-yl)benzyl)pyrrolidine-2-carboxamide; L-Prolinamide, N-[3-[2-[(5Z)-5-[[4-[4-cyano-2-(trifluoromethyl)phenoxy]-3-methoxyphenyl]methylene]-2,4-dioxo-3-thiazolidinyl]ethoxy]-1-oxopropyl]-3-methyl-L-valyl-4-hydroxy-N-[[4-(4-methyl-5-thiazolyl)phenyl]methyl]-, (4R)-; N-(3-{2-[(5Z)-5-{4-[4-Cyano-2-(trifluoromethyl)phenoxy]-3-methoxybenzylidene}-2,4-dioxo-1,3-thiazolidin-3-yl]ethoxy}propanoyl)-3-methyl-L-valyl-(4R)-4-hydroxy-N-[4-(4-methyl-1,3-thiazol-5-yl)benzyl]-L-prolinamide; PROTAC_ERRa; PROTAC_ERRalpha

Density

1.44±0.1 g/cm3

InChI Key

IIJORMBEWMYDEN-FRKKMCEPSA-N

InChI

InChI=1S/C46H47F3N6O9S2/c1-26-39(65-25-52-26)30-10-6-27(7-11-30)23-51-41(58)33-21-31(56)24-55(33)43(60)40(45(2,3)4)53-38(57)14-16-63-17-15-54-42(59)37(66-44(54)61)20-28-8-13-35(36(19-28)62-5)64-34-12-9-29(22-50)18-32(34)46(47,48)49/h6-13,18-20,25,31,33,40,56H,14-17,21,23-24H2,1-5H3,(H,51,58)(H,53,57)/b37-20-/t31-,33+,40-/m1/s1

SMILES

CC1=C(SC=N1)C2=CC=C(C=C2)CNC(=O)C3CC(CN3C(=O)C(C(C)(C)C)NC(=O)CCOCCN4C(=O)C(=CC5=CC(=C(C=C5)OC6=C(C=C(C=C6)C#N)C(F)(F)F)OC)SC4=O)O

Mechanism

Target: PROTAC_ERRα selectively targets estrogen-related receptor alpha for proteasomal degradation.

Binding site: Its ERRα ligand binds the receptor ligand-binding domain.

Mechanism of action: PROTAC_ERRα is a potent VHL-recruiting degrader designed to selectively deplete estrogen-related receptor alpha. The compound connects an ERRα ligand to a von Hippel-Lindau ligand, enabling recruitment of ERRα to VHL-containing ubiquitin ligase machinery. Productive ternary-complex formation promotes ERRα ubiquitination and proteasome-dependent degradation, with reported reduction of ERRα protein levels by more than 80% in cellular systems. PROTAC_ERRα is useful for studying nuclear receptor degradation, ERRα transcriptional programs, downstream target-gene regulation, proteasome-dependent turnover, and differences between receptor inhibition and complete protein depletion.

Applications

• PROTAC-Mediated ERRα Degradation: This product is designed to facilitate the selective degradation of Estrogen-Related Receptor Alpha (ERRα), allowing researchers to study its role in cellular metabolism and energy homeostasis. By leveraging the PROTAC technology, it provides a powerful tool for dissecting ERRα's biological functions through targeted protein degradation.

• Targeted Degradation in Cancer Research: PROTAC_ERRα enables the exploration of ERRα as a potential therapeutic target in cancer. Its ability to specifically degrade ERRα can help elucidate its involvement in tumor progression and metabolic reprogramming, offering insights into novel anti-cancer strategies.

• Functional Study of Nuclear Receptors: Utilizing PROTAC_ERRα allows for the precise modulation of ERRα levels, aiding in the investigation of nuclear receptor signaling pathways. This targeted degradation approach is pivotal for understanding the regulatory mechanisms governing gene expression and receptor-mediated transcriptional control.

• Exploration of Metabolic Pathways: By employing PROTAC_ERRα, researchers can dissect the involvement of ERRα in various metabolic pathways. This targeted degradation tool is essential for studying the receptor’s impact on mitochondrial function and energy expenditure, providing a deeper understanding of metabolic diseases.

1. Catalytic in vivo protein knockdown by small-molecule PROTACs.

Bondeson, D.P., Mares, A., Smith, I.E., Ko, E., Campos, S., Miah, A.H., Mulholland, K.E., Routly, N., Buckley, D.L., Gustafson, J.L. and Zinn, N., 2015. Nature chemical biology, 11(8), pp.611-617.

The current predominant therapeutic paradigm is based on maximizing drug-receptor occupancy to achieve clinical benefit. This strategy, however, generally requires excessive drug concentrations to ensure sufficient occupancy, often leading to adverse side effects. Here, we describe major improvements to the proteolysis targeting chimeras (PROTACs) method, a chemical knockdown strategy in which a heterobifunctional molecule recruits a specific protein target to an E3 ubiquitin ligase, resulting in the target's ubiquitination and degradation. These compounds behave catalytically in their ability to induce the ubiquitination of super-stoichiometric quantities of proteins, providing efficacy that is not limited by equilibrium occupancy. We present two PROTACs that are capable of specifically reducing protein levels by >90% at nanomolar concentrations. In addition, mouse studies indicate that they provide broad tissue distribution and knockdown of the targeted protein in tumor xenografts. Together, these data demonstrate a protein knockdown system combining many of the favorable properties of small-molecule agents with the potent protein knockdown of RNAi and CRISPR.

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