Name: BSJ-04-132
Brand: BOC Sciences
Rating: 5 (1 reviews)

Size

Price

Stock

Quantity

$--

In stock

Purity

≥95%

Solubility

Soluble in DMSO

Storage

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

IUPACName

7-cyclopentyl-2-[[5-[4-[4-[[2-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]oxyacetyl]amino]butyl]piperazin-1-yl]pyridin-2-yl]amino]-N,N-dimethylpyrrolo[2,3-d]pyrimidine-6-carboxamide

Synonyms

7-cyclopentyl-2-((5-(4-(4-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)oxy)acetamido)butyl)piperazin-1-yl)pyridin-2-yl)amino)-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide; 7H-Pyrrolo[2,3-d]pyrimidine-6-carboxamide, 7-cyclopentyl-2-[[5-[4-[4-[[2-[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]oxy]acetyl]amino]butyl]-1-piperazinyl]-2-pyridinyl]amino]-N,N-dimethyl-; 7-Cyclopentyl-2-[[5-[4-[4-[[2-[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]oxy]acetyl]amino]butyl]-1-piperazinyl]-2-pyridinyl]amino]-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide

Density

1.49±0.1 g/cm3

InChI Key

GWLSXEHHNOBFOI-UHFFFAOYSA-N

InChI

InChI=1S/C42H49N11O7/c1-49(2)40(58)31-22-26-23-45-42(48-37(26)52(31)27-8-3-4-9-27)46-33-14-12-28(24-44-33)51-20-18-50(19-21-51)17-6-5-16-43-35(55)25-60-32-11-7-10-29-36(32)41(59)53(39(29)57)30-13-15-34(54)47-38(30)56/h7,10-12,14,22-24,27,30H,3-6,8-9,13,15-21,25H2,1-2H3,(H,43,55)(H,47,54,56)(H,44,45,46,48)

SMILES

CN(C)C(=O)C1=CC2=CN=C(NC3=CC=C(N4CCN(CCCCNC(=O)COC5=CC=CC6=C5C(=O)N(C5CCC(=O)NC5=O)C6=O)CC4)C=N3)N=C2N1C1CCCC1

Mechanism

Target: BSJ-04-132 selectively targets CDK4 while sparing CDK6 and IKZF1/3 degradation.

Binding site: Its ribociclib-derived ligand binds the ATP pocket of CDK4/cyclin D1.

Mechanism of action: BSJ-04-132 is a ribociclib-based, cereblon-recruiting CDK4 PROTAC designed to achieve selective CDK4 degradation. Although its kinase ligand can biochemically engage CDK4/cyclin D1 and CDK6/cyclin D1, reported cellular studies indicate preferential degradation of CDK4 without detectable CDK6 or IKZF1/3 depletion. This profile makes BSJ-04-132 useful for separating CDK4-specific functions from CDK6 biology and CRBN neosubstrate effects. In targeted degradation workflows, it supports studies of G1 cell-cycle control, RB phosphorylation, CDK4 dependency, degradation selectivity, and ribociclib-scaffold PROTAC optimization.

Applications

• PROTAC-Mediated Cancer Research: BSJ-04-132 is utilized in cancer research to facilitate the targeted degradation of oncogenic proteins. This approach enables the investigation of protein function and the validation of potential therapeutic targets, offering insights into novel cancer treatment strategies through selective protein elimination.

• Targeted Degradation in Neurodegenerative Studies: Researchers employ BSJ-04-132 to study neurodegenerative diseases by degrading proteins implicated in disease progression. This aids in understanding the molecular mechanisms underlying these disorders and in identifying new therapeutic avenues for intervention.

• Signal Transduction Pathway Analysis: BSJ-04-132 is applied to dissect signal transduction pathways by selectively degrading key signaling proteins. This allows for detailed exploration of cellular communication processes and the identification of critical nodes for therapeutic targeting.

• Drug Resistance Mechanism Exploration: By using BSJ-04-132, scientists can degrade proteins associated with drug resistance, enabling the study of resistance mechanisms and the development of strategies to overcome therapeutic challenges in various diseases.

1. 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.

2. Mapping the degradable kinome provides a resource for expedited degrader development.

Donovan, K.A., Ferguson, F.M., Bushman, J.W., Eleuteri, N.A., Bhunia, D., Ryu, S., Tan, L., Shi, K., Yue, H., Liu, X. and Dobrovolsky, D., 2020. Cell, 183(6), pp.1714-1731.

Targeted protein degradation (TPD) refers to the use of small molecules to induce ubiquitin-dependent degradation of proteins. TPD is of interest in drug development, as it can address previously inaccessible targets. However, degrader discovery and optimization remains an inefficient process due to a lack of understanding of the relative importance of the key molecular events required to induce target degradation. Here, we use chemo-proteomics to annotate the degradable kinome. Our expansive dataset provides chemical leads for ~200 kinases and demonstrates that the current practice of starting from the highest potency binder is an ineffective method for discovering active compounds. We develop multitargeted degraders to answer fundamental questions about the ubiquitin proteasome system, uncovering that kinase degradation is p97 dependent. This work will not only fuel kinase degrader discovery, but also provides a blueprint for evaluating targeted degradation across entire gene families to accelerate understanding of TPD beyond the kinome.

Stock concentration: *

Desired final volume: *

Desired concentration: *

* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C₁V₁ = C₂V₂