Name: dBET23
Brand: BOC Sciences
Rating: 5 (1 reviews)

Size

Price

Stock

Quantity

$--

In stock

Purity

≥95%

Solubility

Soluble in DMSO

Appearance

Solid Powder

Storage

Store at 2-8°C for short term (days to weeks) or -20°C for long term (months to years)

IUPACName

methyl 2-[(9S)-7-(4-chlorophenyl)-4-[8-[[2-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]oxyacetyl]amino]octylcarbamoyl]-5,13-dimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetate

Synonyms

dBET-23; dBET 23; methyl 2-((6S)-4-(4-chlorophenyl)-2-((8-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetamido)octyl)carbamoyl)-3,9-dimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetate; Methyl [(6S)-4-(4-chlorophenyl)-2-({8-[({[2-(2,6-dioxo-3-piperidinyl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl]oxy}acetyl)amino]octyl}carbamoyl)-3,9-dimethyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl]acetate; 6H-Thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine-6-acetic acid, 4-(4-chlorophenyl)-2-[[[8-[[2-[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]oxy]acetyl]amino]octyl]amino]carbonyl]-3,9-dimethyl-, methyl ester, (6S)-

Density

1.50±0.1 g/cm3 (Predicted)

InChI Key

ZIHIUFZFPMILIG-XLTVJXRZSA-N

InChI

InChI=1S/C43H45ClN8O9S/c1-23-34-36(25-13-15-26(44)16-14-25)47-28(21-33(55)60-3)38-50-49-24(2)51(38)43(34)62-37(23)40(57)46-20-9-7-5-4-6-8-19-45-32(54)22-61-30-12-10-11-27-35(30)42(59)52(41(27)58)29-17-18-31(53)48-39(29)56/h10-16,28-29H,4-9,17-22H2,1-3H3,(H,45,54)(H,46,57)(H,48,53,56)/t28-,29?/m0/s1

SMILES

CC1=C(SC2=C1C(=NC(C3=NN=C(N32)C)CC(=O)OC)C4=CC=C(C=C4)Cl)C(=O)NCCCCCCCCNC(=O)COC5=CC=CC6=C5C(=O)N(C6=O)C7CCC(=O)NC7=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: dBET23 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 Degradation of BET Proteins: dBET23 is a potent PROTAC designed to target and degrade BET family proteins, such as BRD4. This application is pivotal for studying transcriptional regulation and epigenetic modifications, offering insights into the role of BET proteins in cancer and other diseases.

• Targeted Protein Degradation in Cancer Research: By selectively degrading BET proteins, dBET23 provides a valuable tool for investigating the pathways involved in oncogenesis. Researchers can utilize this capability to explore novel therapeutic strategies and understand the molecular underpinnings of tumor progression.

• Studying Epigenetic Modulation: dBET23 facilitates the examination of epigenetic landscapes by enabling the targeted degradation of epigenetic regulators. This application is essential for deciphering the complex interactions within chromatin and their implications in gene expression and cellular differentiation.

• Exploring Mechanisms of Action: The use of dBET23 in targeted protein degradation studies allows researchers to dissect the mechanisms underlying protein-protein interactions and signal transduction pathways, thereby advancing the understanding of cellular processes and identifying potential drug targets.

1. Plasticity in binding confers selectivity in ligand-induced protein degradation.

Nowak, R.P., DeAngelo, S.L., Buckley, D., He, Z., Donovan, K.A., An, J., Safaee, N., Jedrychowski, M.P., Ponthier, C.M., Ishoey, M. and Zhang, T., 2018. Nature chemical biology, 14(7), pp.706-714.

Heterobifunctional small-molecule degraders that induce protein degradation through ligase-mediated ubiquitination have shown considerable promise as a new pharmacological modality. However, we currently lack a detailed understanding of the molecular basis for target recruitment and selectivity, which is critically required to enable rational design of degraders. Here we utilize a comprehensive characterization of the ligand-dependent CRBN-BRD4 interaction to demonstrate that binding between proteins that have not evolved to interact is plastic. Multiple X-ray crystal structures show that plasticity results in several distinct low-energy binding conformations that are selectively bound by ligands. We demonstrate that computational protein-protein docking can reveal the underlying interprotein contacts and inform the design of a BRD4 selective degrader that can discriminate between highly homologous BET bromodomains. Our findings that plastic interprotein contacts confer selectivity for ligand-induced protein dimerization provide a conceptual framework for the development of heterobifunctional ligands.

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