Name: PROTAC CDK2/9 Degrader-1
Brand: BOC Sciences
Rating: 5 (1 reviews)

Size

Price

Stock

Quantity

$--

In stock

Purity

≥99%

Solubility

Soluble in DMSO

Appearance

Powder

Storage

Store at -20°C

IUPACName

N-[4-[[4-[4-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethylamino]-4-oxobutanoyl]piperazin-1-yl]methyl]phenyl]-4-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-1H-pyrazole-5-carboxamide

Synonyms

N-{4-[(4-{4-[(2-{[2-(2,6-Dioxo-3-piperidinyl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl]amino}ethyl)amino]-4-oxobutanoyl}-1-piperazinyl)methyl]phenyl}-4-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-1H-pyrazole-3-carboxamide; 1-Piperazinebutanamide, N-[2-[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]amino]ethyl]-γ-oxo-4-[[4-[[[4-(7H-pyrrolo[2,3-d]pyrimidin-4-ylamino)-1H-pyrazol-3-yl]carbonyl]amino]phenyl]methyl]-

Density

1.534±0.06 g/cm3

InChI Key

BRYMZSSAIDEFEM-UHFFFAOYSA-N

InChI

InChI=1S/C40H41N13O7/c54-30(42-15-14-41-27-3-1-2-25-33(27)40(60)53(39(25)59)29-8-9-31(55)49-37(29)57)10-11-32(56)52-18-16-51(17-19-52)21-23-4-6-24(7-5-23)47-38(58)34-28(20-46-50-34)48-36-26-12-13-43-35(26)44-22-45-36/h1-7,12-13,20,22,29,41H,8-11,14-19,21H2,(H,42,54)(H,46,50)(H,47,58)(H,49,55,57)(H2,43,44,45,48)

SMILES

C1CC(=O)NC(=O)C1N2C(=O)C3=C(C2=O)C(=CC=C3)NCCNC(=O)CCC(=O)N4CCN(CC4)CC5=CC=C(C=C5)NC(=O)C6=C(C=NN6)NC7=NC=NC8=C7C=CN8

Mechanism

Target: Targets CDK2 and CDK9 cyclin-dependent kinases for experimental targeted protein degradation studies.

Binding Site: Binds the CDK ATP-binding pocket and recruited E3 ligase ligand site to support productive ternary complex formation.

Mechanism of Action: PROTAC CDK2/9 Degrader-1 is designed for use in PROTAC or targeted protein degradation experiments directed toward CDK2 and CDK9 cyclin-dependent kinases. 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 CDK2/9 Degradation: This product serves as a potent tool for selectively degrading cyclin-dependent kinases 2 and 9, allowing researchers to dissect their roles in cell cycle regulation and transcriptional control. By inducing targeted protein degradation, it facilitates the study of CDK2/9-driven pathways and their implications in oncogenesis.

• Cell Cycle Regulation Studies: Utilizing PROTAC CDK2/9 Degrader-1 enables precise modulation of cell cycle dynamics by degrading key kinases involved in cell cycle progression. Researchers can explore the mechanistic details of CDK2/9 activity, providing insights into potential vulnerabilities in cancer cells reliant on these kinases.

• Transcriptional Control Investigation: By targeting CDK9, this degrader aids in understanding its role in transcription elongation and RNA polymerase II regulation. This application is crucial for elucidating transcriptional dysregulation in diseases, offering a pathway to identifying novel therapeutic targets through targeted protein degradation.

• Oncology Research Applications: The selective degradation of CDK2/9 via PROTAC technology allows for the exploration of their contributions to tumorigenesis. Researchers can investigate the therapeutic potential of targeting these kinases in cancer, advancing the development of new strategies for targeted cancer therapy.

1. Development of selective mono or dual PROTAC degrader probe of CDK isoforms.

Zhou, F., Chen, L., Cao, C., Yu, J., Luo, X., Zhou, P., Zhao, L., Du, W., Cheng, J., Xie, Y. and Chen, Y., 2020. European Journal of Medicinal Chemistry, 187, p.111952.

Cyclin-dependent kinase (CDK) family members are promising molecular targets in discovering potent inhibitors in disease settings, they function differentially. CDK2, CDK4 and CDK6, directly regulate the cell cycle, while CDK9 primarily modulates the transcription regulation. In discovering inhibitors of these CDKs, toxicity associated with off-target effect on other CDK homologs often posts as a clinical issue and hinders their further therapeutic development. To improve efficacy and reduce toxicity, here, using the Proteolysis Targeted Chimeras (PROTACs) approach, we design and further optimize small molecule degraders targeting multiple CDKs. We showed that heterobifunctional compound A9 selectively degraded CDK2. We also identified a dual-degrader, compound F3, which potently induced degradation of both CDK2 (DC50: 62 nM) and CDK9 (DC50: 33 nM). In human prostate cancer PC-3 cells, compound F3 potently inhibits cell proliferation by effectively blocking the cell cycle in S and G2/M phases. Our preliminary data suggests that PROTAC-oriented CDK2/9 degradation is potentially an effective therapeutic approach.

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It is commonly abbreviated as: C₁V₁ = C₂V₂