Name: dCBP-1
Brand: BOC Sciences
Rating: 5 (1 reviews)

Size

Price

Stock

Quantity

$--

In stock

Purity

≥95%

Solubility

DMSO: 50 mg/mL (48.63 mM; ultrasonic and warming and heat to 80°C)

Appearance

Solid

Storage

Store at -20°C, sealed storage, away from moisture and light

IUPACName

3-[7-(difluoromethyl)-6-(1-methylpyrazol-4-yl)-3,4-dihydro-2H-quinolin-1-yl]-1-[1-[3-[2-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]amino]ethoxy]ethoxy]ethoxy]ethoxy]propanoyl]piperidin-4-yl]-N-methyl-6,7-dihydro-4H-pyrazolo[4,3-c]pyridine-5-carboxamide

Synonyms

5H-Pyrazolo[4,3-c]pyridine-5-carboxamide, 3-[7-(difluoromethyl)-3,4-dihydro-6-(1-methyl-1H-pyrazol-4-yl)-1(2H)-quinolinyl]-1-[1-[15-[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-5-yl]amino]-1-oxo-4,7,10,13-tetraoxapentadec-1-yl]-4-piperidinyl]-1,4,6,7-tetrahydro-N-methyl-; 3-[7-(Difluoromethyl)-6-(1-methyl-1H-pyrazol-4-yl)-3,4-dihydro-1(2H)-quinolinyl]-1-[1-(15-{[2-(2,6-dioxo-3-piperidinyl)-1,3-dioxo-2,3-dihydro-1H-isoindol-5-yl]amino}-4,7,10,13-tetraoxapentadecan-1-oyl)-4-piperidinyl]-N-methyl-1,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carboxamide

Density

1.5±0.1 g/cm3

InChI Key

ILVRLRGBSSFKIE-UHFFFAOYSA-N

InChI

InChI=1S/C51H63F2N11O10/c1-54-51(70)61-17-11-41-40(31-61)47(62-14-3-4-32-26-37(33-29-56-59(2)30-33)38(46(52)53)28-43(32)62)58-64(41)35-9-15-60(16-10-35)45(66)12-18-71-20-22-73-24-25-74-23-21-72-19-13-55-34-5-6-36-39(27-34)50(69)63(49(36)68)42-7-8-44(65)57-48(42)67/h5-6,26-30,35,42,46,55H,3-4,7-25,31H2,1-2H3,(H,54,70)(H,57,65,67)

SMILES

CNC(=O)N1CCC2=C(C1)C(=NN2C3CCN(CC3)C(=O)CCOCCOCCOCCOCCNC4=CC5=C(C=C4)C(=O)N(C5=O)C6CCC(=O)NC6=O)N7CCCC8=CC(=C(C=C87)C(F)F)C9=CN(N=C9)C

Mechanism

Target: Targets CBP and p300 bromodomain acetyltransferase paralogs for experimental targeted protein degradation studies.

Binding Site: Binds the CBP/p300 bromodomain acetyl-lysine pocket and cereblon-binding phthalimide motif to support productive ternary complex formation.

Mechanism of Action: dCBP-1 is designed for use in PROTAC or targeted protein degradation experiments directed toward CBP and p300 bromodomain acetyltransferase paralogs. 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 CBP Degradation: dCBP-1 is a potent PROTAC designed to specifically target and degrade the CREB-binding protein (CBP) in cellular models. This enables researchers to investigate the role of CBP in transcriptional regulation and its implications in various biological processes, providing insights into potential therapeutic targets for diseases involving dysregulated gene expression.

• Targeted Protein Degradation in Cancer Research: Utilizing dCBP-1 allows for the selective degradation of CBP, offering a robust tool for studying its contribution to oncogenic pathways. By modulating CBP levels, researchers can explore its involvement in cancer progression and identify novel intervention strategies for CBP-dependent malignancies.

• Epigenetic Modulation Studies: dCBP-1 facilitates the targeted degradation of CBP, a key epigenetic regulator, enabling detailed analysis of its role in chromatin remodeling and gene expression. This application is crucial for understanding the epigenetic mechanisms underlying cellular differentiation and development, as well as their dysregulation in disease states.

• Investigating Protein-Protein Interactions: By employing dCBP-1, scientists can degrade CBP and assess the downstream effects on its interacting partners. This approach aids in delineating complex protein interaction networks and understanding the functional consequences of CBP loss, thereby advancing the study of cellular signaling pathways.

1. Targeted degradation of the enhancer lysine acetyltransferases CBP and p300

Jan Sayilgan,Robert Morris,Samuel Ojeda,Johannes Kreuzer,Michael Lawrence,Sumit Rai,Xcanda Ixchel Herrera Lopez,Eileen Hu,Barbara Karakyriakou,Raghu Vannam,Christopher J Ott,Wilhelm Haas Cell Chem Biol . 2021 Apr 15;28(4):503-514.e12. doi: 10.1016/j.chembiol.2020.12.004.

The enhancer factors CREB-binding protein (CBP) and p300 (also known as KAT3A and KAT3B) maintain gene expression programs through lysine acetylation of chromatin and transcriptional regulators and by scaffolding functions mediated by several protein-protein interaction domains. Small molecule inhibitors that target some of these domains have been developed; however, they cannot completely ablate p300/CBP function in cells. Here we describe a chemical degrader of p300/CBP, dCBP-1. Leveraging structures of ligand-bound p300/CBP domains, we use in silico modeling of ternary complex formation with the E3 ubiquitin ligase cereblon to enable degrader design. dCBP-1 is exceptionally potent at killing multiple myeloma cells and can abolish the enhancer that drives MYC oncogene expression. As an efficient degrader of this unique class of acetyltransferases, dCBP-1 is a useful tool alongside domain inhibitors for dissecting the mechanism by which these factors coordinate enhancer activity in normal and diseased cells.

2. Chemical control of multidomain acetyltransferase activity

Jordan L Meier,Yihang Jing,Whitney K Lieberman Cell Chem Biol . 2021 Apr 15;28(4):433-435. doi: 10.1016/j.chembiol.2021.03.015.

Chromatin-modifying lysine acetyltransferases employ multiple protein domains to regulate transcription. In this issue, Vannam et al. (2021) describe dCBP-1, a small molecule degrader of the multidomain acetyltransferases EP300 and CREBBP. This provides a new tool for interrogating EP300/CREBBP function and also suggests a strategy for pharmacological differentiation of acetyltransferase paralogs.

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