Name: PROTAC BRD2/BRD4 degrader-1
Brand: BOC Sciences
Rating: 5 (1 reviews)

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Price

Stock

Quantity

$--

In stock

Solubility

Soluble in DMSO

IUPACName

N-[4-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]butyl]-3-[6-[(2-methoxyphenyl)sulfonylamino]-1-methyl-2-oxobenzo[cd]indol-4-yl]propanamide

Synonyms

NSC-812346; N-(4-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)butyl)-3-(6-((2-methoxyphenyl)sulfonamido)-1-methyl-2-oxo-1,2-dihydrobenzo[cd]indol-4-yl)propanamide; Benz[cd]indole-4-propanamide, N-[4-[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]amino]butyl]-1,2-dihydro-6-[[(2-methoxyphenyl)sulfonyl]amino]-1-methyl-2-oxo-; N-[4-[[2-(2,6-Dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]amino]butyl]-1,2-dihydro-6-[[(2-methoxyphenyl)sulfonyl]amino]-1-methyl-2-oxobenz[cd]indole-4-propanamide

Density

1.466±0.06 g/cm3

InChI Key

DCPKSVYPNGBDSB-UHFFFAOYSA-N

InChI

InChI=1S/C39H38N6O9S/c1-44-28-14-13-26(43-55(52,53)31-11-4-3-10-30(31)54-2)24-20-22(21-25(34(24)28)37(44)49)12-16-32(46)41-19-6-5-18-40-27-9-7-8-23-35(27)39(51)45(38(23)50)29-15-17-33(47)42-36(29)48/h3-4,7-11,13-14,20-21,29,40,43H,5-6,12,15-19H2,1-2H3,(H,41,46)(H,42,47,48)

SMILES

CN1C2=C3C(=CC(=CC3=C(C=C2)NS(=O)(=O)C4=CC=CC=C4OC)CCC(=O)NCCCCNC5=CC=CC6=C5C(=O)N(C6=O)C7CCC(=O)NC7=O)C1=O

Mechanism

Target: Targets BET bromodomain proteins, especially BRD4, BRD3, and BRD2 for experimental targeted protein degradation studies.

Binding Site: Binds the BET bromodomain acetyl-lysine pocket and recruited E3 ligase ligand site to support productive ternary complex formation.

Mechanism of Action: PROTAC BRD2/BRD4 degrader-1 is designed for use in PROTAC or targeted protein degradation experiments directed toward BET bromodomain proteins, especially BRD4, BRD3, and BRD2. 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 BRD2 Degradation: This product enables researchers to selectively degrade BRD2, a bromodomain-containing protein involved in transcriptional regulation. By employing PROTAC technology, scientists can study the functional consequences of BRD2 depletion in various cellular contexts, providing insights into its role in gene expression and potential as a therapeutic target.

• Targeted Degradation of BRD4: Utilizing PROTAC BRD2/BRD4 degrader-1 allows for precise degradation of BRD4, a key player in chromatin remodeling and transcriptional elongation. This application aids in dissecting BRD4's involvement in oncogenic processes and epigenetic regulation, offering a valuable tool for cancer research and drug discovery.

• Dual BRD2/BRD4 Protein Targeting: This PROTAC compound facilitates simultaneous degradation of BRD2 and BRD4, enabling the study of their combined effects on cellular pathways. Researchers can explore synergistic interactions and dependencies within signaling networks, advancing the understanding of bromodomain biology and potential therapeutic interventions.

• Mechanistic Studies in Epigenetics: PROTAC BRD2/BRD4 degrader-1 serves as a powerful tool for investigating the mechanistic roles of bromodomain proteins in epigenetic regulation. By inducing targeted protein degradation, researchers can unravel complex epigenetic modifications and their implications for gene expression and cellular differentiation.

1. Discovery of novel small molecule induced selective degradation of the bromodomain and extra-terminal (BET) bromodomain protein BRD4 and BRD2 with cellular potencies.

Jiang, F., Wei, Q., Li, H., Li, H., Cui, Y., Ma, Y., Chen, H., Cao, P., Lu, T. and Chen, Y., 2020. Bioorganic & Medicinal Chemistry, 28(1), p.115181.

The BET proteins BRD2, BRD3, and BRD4 play important roles in transcriptional regulation and can be degraded by proteolysis-targeting chimeras (PROTACs) for BET proteins. However, the lack of intra-BET proteins selectivity limits the scope of current degraders as probes for target validation and could lead to unwanted side effects or toxicity in a therapeutic setting. We describe herein the design, synthesis, and evaluation of PROTAC BET degraders, based on the BET inhibitor with selectivity for the first Bromodomain benzo[cd]indole-2-one, alkylamide linker and cereblon ligand thalidomide. Compound 15 potently and rapidly induces reversible, long-lasting, and unexpectedly selective removal of BRD4 and BRD2 over BRD3, which not only effectively inhibits cell growth in human acute leukemia cell lines, but also very effective in inhibiting solid tumors with low cytotoxic effect in the cell profiles of NCI 60 cell lines. Remarkable dependency on linker length was observed for BRD4-degrading and c-Myc-driven antiproliferative activities in acute myeloid leukemia cell line MV4-11. The small-molecular 15 represents a novel, potent, and selective class of BRD4 and BRD2 degraders for the development of therapeutics to treat cancers.

What kind of advantages does it has?

BRD4 and BRD2 are overactive in many cancers, and their inhibition has shown promising anti-tumor effects in various cancer models. PROTAC BRD2/BRD4 degrader-1's ability to degrade these proteins could potentially lead to more effective cancer treatments than traditional inhibitors. Additionally, its selectivity towards BRD4 and BRD2 over other closely related proteins like BRD3 could potentially reduce side effects.

22/5/2017

How does it work?

Unlike traditional drugs that simply inhibit BRD4 and BRD2 activity, PROTAC BRD2/BRD4 degrader-1 actually recruits these proteins to another protein called cereblon. Cereblon acts like a garbage disposal for the cell, tagging the bound BRD4 and BRD2 for degradation. This results in a more pronounced and long-lasting reduction in BRD4 and BRD2 levels compared to traditional inhibitors.

17/1/2023

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