Name: BSJ-03-123
Brand: BOC Sciences
Price: 399 USD
Availability: MadeToOrder

Purity

≥95%

Solubility

Soluble in DMSO

Appearance

Yellow Solid

Storage

Store at -20°C

Shipping

Room temperature in continental US; may vary elsewhere

IUPACName

N-[2-[2-[2-[2-[4-[6-[(6-acetyl-8-cyclopentyl-5-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl)amino]pyridin-3-yl]piperazin-1-yl]ethoxy]ethoxy]ethoxy]ethyl]-2-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]oxyacetamide

Synonyms

BSJ 03-123; BSJ 03 123; BSJ-03 123; BSJ03123; N-[2-(2-{2-[2-(4-{6-[(6-Acetyl-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino]-3-pyridinyl}-1-piperazinyl)ethoxy]ethoxy}ethoxy)ethyl]-2-{[2-(2,6-dioxo-3-piperidinyl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl]oxy}acetamide; Acetamide, N-[2-[2-[2-[2-[4-[6-[(6-acetyl-8-cyclopentyl-7,8-dihydro-5-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl)amino]-3-pyridinyl]-1-piperazinyl]ethoxy]ethoxy]ethoxy]ethyl]-2-[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]oxy]-

Density

1.375±0.06 g/cm3 (Predicted)

InChI Key

LUHCYAOYQIFNRN-UHFFFAOYSA-N

InChI

InChI=1S/C47H56N10O11/c1-29-34-27-50-47(53-42(34)56(31-6-3-4-7-31)45(63)40(29)30(2)58)51-37-12-10-32(26-49-37)55-17-15-54(16-18-55)19-21-66-23-25-67-24-22-65-20-14-48-39(60)28-68-36-9-5-8-33-41(36)46(64)57(44(33)62)35-11-13-38(59)52-43(35)61/h5,8-10,12,26-27,31,35H,3-4,6-7,11,13-25,28H2,1-2H3,(H,48,60)(H,52,59,61)(H,49,50,51,53)

SMILES

CC1=C(C(=O)N(C2=NC(=NC=C12)NC3=NC=C(C=C3)N4CCN(CC4)CCOCCOCCOCCNC(=O)COC5=CC=CC6=C5C(=O)N(C6=O)C7CCC(=O)NC7=O)C8CCCC8)C(=O)C

Mechanism

Target: Targets CDK6 for experimental targeted protein degradation studies.

Binding Site: Binds the CDK6 ATP-binding pocket and CRBN cereblon ligand-binding domain to support productive ternary complex formation.

Mechanism of Action: BSJ-03-123 is designed for use in PROTAC or targeted protein degradation experiments directed toward CDK6. 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 Kinase Degradation: BSJ-03-123 facilitates the selective degradation of specific kinases, offering a robust tool for dissecting kinase signaling pathways. Researchers can employ this PROTAC to study the functional consequences of kinase removal, advancing the understanding of kinase roles in cellular processes and disease states.

• Targeted Protein Degradation in Oncology: Utilizing BSJ-03-123 allows for the precise degradation of oncogenic proteins, presenting a novel approach in cancer research. By eliminating proteins that drive tumorigenesis, this PROTAC aids in exploring new therapeutic strategies and elucidating mechanisms of cancer progression.

• Investigating Protein-Protein Interactions: BSJ-03-123 serves as a valuable probe for studying protein-protein interactions through targeted protein degradation. By degrading specific protein complexes, researchers can gain insights into interaction dynamics and the structural basis of complex formation, enhancing the understanding of cellular machinery.

• Modulating Cellular Pathways: With BSJ-03-123, researchers can modulate specific cellular pathways by degrading key regulatory proteins. This application is crucial for dissecting pathway components and understanding their roles in cellular homeostasis and disease, paving the way for novel intervention strategies.

1. Homolog-Selective Degradation as a Strategy to Probe the Function of CDK6 in AML.

Brand, M., Jiang, B., Bauer, S., Donovan, K.A., Liang, Y., Wang, E.S., Nowak, R.P., Yuan, J.C., Zhang, T., Kwiatkowski, N. and Müller, A.C., 2019. Cell chemical biology, 26(2), pp.300-306.

The design of selective small molecules is often stymied by similar ligand binding pockets. Here, we report BSJ-03-123, a phthalimide-based degrader that exploits protein-interface determinants to achieve proteome-wide selectivity for the degradation of cyclin-dependent kinase 6 (CDK6). Pharmacologic CDK6 degradation targets a selective dependency of acute myeloid leukemia cells, and transcriptomics and phosphoproteomics profiling of acute degradation of CDK6 enabled dynamic mapping of its immediate role in coordinating signaling and transcription.

2. Development of dual and selective degraders of cyclin-dependent kinases 4 and 6.

Jiang, B., Wang, E.S., Donovan, K.A., Liang, Y., Fischer, E.S., Zhang, T. and Gray, N.S., 2019. Angewandte Chemie International Edition, 58(19), pp.6321-6326.

Cyclin-dependent kinases 4 and 6 (CDK4/6) are key regulators of the cell cycle, and there are FDA-approved CDK4/6 inhibitors for treating patients with metastatic breast cancer. However, due to conservation of their ATP-binding sites, development of selective agents has remained elusive. Here, we report imide-based degrader molecules capable of degrading both CDK4/6, or selectively degrading either CDK4 or CDK6. We were also able to tune the activity of these molecules against Ikaros (IKZF1) and Aiolos (IKZF3), which are well-established targets of imide-based degraders. We found that in mantle cell lymphoma cell lines, combined IKZF1/3 degradation with dual CDK4/6 degradation produced enhanced anti-proliferative effects compared to CDK4/6 inhibition, CDK4/6 degradation, or IKZF1/3 degradation. In summary, we report here the first compounds capable of inducing selective degradation of CDK4 and CDK6 as tools to pharmacologically dissect their distinct biological functions.

Hi,good afternoon, do you know something about this compound? would you please give me an introduction?

Key Properties of BSJ-03-123: High potency: BSJ-03-123 effectively degrades CDK6 at very low concentrations, making it a powerful tool for researchers. Selective targeting: BSJ-03-123 primarily targets CDK6 without significantly affecting other proteins, reducing potential side effects. Rapid degradation: BSJ-03-123 quickly triggers CDK6 degradation, allowing for rapid modulation of its activity in cells.

8/5/2021

Dear sir, would you please suggest its application? thanks.

Potential Applications of BSJ-03-123: Cancer therapy: BSJ-03-123 is being investigated for its potential to treat various cancers, particularly those where CDK6 is overactive or plays a critical role in tumor growth. Chemical biology: BSJ-03-123 serves as a valuable tool for studying the function of CDK6 and its role in different cellular processes. Drug discovery: The mechanism of action of BSJ-03-123 could inspire the development of new targeted therapies for cancer and other diseases.

8/5/2021

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