Name: PROTAC B-Raf degrader 1
Brand: BOC Sciences
Rating: 5 (1 reviews)

Size

Price

Stock

Quantity

$--

In stock

Purity

≥95%

Solubility

10 mM in DMSO

Storage

Store at -20°C, stored under nitrogen

Shipping

Room temperature in continental US; may vary elsewhere

IUPACName

N-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]-2-oxoethyl]-2-[2-methoxy-5-[[(E)-2-(2,4,6-trimethoxyphenyl)ethenyl]sulfonylmethyl]anilino]acetamide

Synonyms

(E)-N-(2-(2,6-Dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)-2-(2-((2-methoxy-5-(((2,4,6-trimethoxystyryl)sulfonyl)methyl)phenyl)amino)acetamido)acetamide; N-[2-Methoxy-5-({[(E)-2-(2,4,6-trimethoxyphenyl)vinyl]sulfonyl}methyl)phenyl]glycyl-N-[2-(2,6-dioxo-3-piperidinyl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl]glycinamide; Glycinamide, N-[2-methoxy-5-[[[(E)-2-(2,4,6-trimethoxyphenyl)ethenyl]sulfonyl]methyl]phenyl]glycyl-N-[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]-

Boiling Point

1136.9±65.0°C at 760 Torr

Density

1.451±0.06 g/cm3

InChI Key

AMOFJSISJOOLNX-OUKQBFOZSA-N

InChI

InChI=1S/C36H37N5O12S/c1-50-21-15-28(52-3)22(29(16-21)53-4)12-13-54(48,49)19-20-8-10-27(51-2)25(14-20)37-17-31(43)38-18-32(44)39-24-7-5-6-23-33(24)36(47)41(35(23)46)26-9-11-30(42)40-34(26)45/h5-8,10,12-16,26,37H,9,11,17-19H2,1-4H3,(H,38,43)(H,39,44)(H,40,42,45)/b13-12+

SMILES

COC1=C(C=C(C=C1)CS(=O)(=O)C=CC2=C(C=C(C=C2OC)OC)OC)NCC(=O)NCC(=O)NC3=CC=CC4=C3C(=O)N(C4=O)C5CCC(=O)NC5=O

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: PROTAC B-Raf 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 B-Raf Degradation: This product facilitates the targeted degradation of B-Raf, a key kinase in the MAPK/ERK signaling pathway. By promoting the proteasomal degradation of B-Raf, researchers can investigate its role in cellular proliferation and survival, offering insights into oncogenic signaling mechanisms and potential therapeutic targets in cancer research.

• Signaling Pathway Dissection: Utilizing PROTAC B-Raf degrader 1 allows for precise modulation of B-Raf levels, enabling the dissection of downstream signaling pathways. This aids in understanding the intricate network of kinase interactions and the impact of B-Raf on cellular responses, enhancing studies in signal transduction and molecular biology.

• Functional Proteomics: By employing PROTAC technology to selectively degrade B-Raf, researchers can perform functional proteomic studies to identify compensatory mechanisms and adaptive responses. This approach is instrumental in mapping protein networks and understanding the dynamic nature of cellular proteomes in response to targeted protein degradation.

• Cancer Model Investigations: In cancer research, PROTAC B-Raf degrader 1 serves as a powerful tool to study the effects of B-Raf depletion in various cancer models. It provides a strategic means to evaluate the dependency of tumor cells on B-Raf signaling, assisting in the identification of vulnerabilities and potential therapeutic interventions.

1. Pomalidomide hybrids act as proteolysis targeting chimeras: Synthesis, anticancer activity and B-Raf degradation.

Chen, H., Chen, F., Pei, S. and Gou, S., 2019. Bioorganic chemistry, 87, pp.191-199.

As the first intracellular signaling molecule and the most frequently mutated oncogene, B-Raf represents an important target in cancer therapy. Here we report several pomalidomide hybrids acting as proteolysis targeting chimeras (PROTACs) for the degradation of B-Raf. Due to its high expression of B-Raf, MCF-7 cells are sensitive to these compounds. Among them, compound 2 can effectively kill cancer cells via inducing cells apoptosis. As a B-Raf degrader, compound 2 can accelerate the degradation of B-Raf by recruiting ubiquitin-proteasome system, and further affects the expression of Mcl-1, a downstream protein of B-Raf. The anticancer mechanism of compound 2 is quite different from its mother compound and cancer cells seem to be more sensitive to the degrader, hinting that degradation of B-Raf by PROTAC is a potential way for cancer treatment.

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Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C₁V₁ = C₂V₂