Name: PROTAC CDK9 degrader-2
Brand: BOC Sciences
Rating: 5 (1 reviews)

Size

Price

Stock

Quantity

$--

In stock

Purity

≥95%

Appearance

Light Yellow Solid

IUPACName

8-[4-[(5,7-dihydroxy-4-oxo-2-phenylchromen-8-yl)oxymethyl]triazol-1-yl]-N-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]octanamide

Synonyms

1H-1,2,3-Triazole-1-octanamide, 4-[[(5,7-dihydroxy-4-oxo-2-phenyl-4H-1-benzopyran-8-yl)oxy]methyl]-N-[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]-; 8-(4-{[(5,7-Dihydroxy-4-oxo-2-phenyl-4H-chromen-8-yl)oxy]methyl}-1H-1,2,3-triazol-1-yl)-N-[2-(2,6-dioxo-3-piperidinyl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl]octanamide; 4-[[(5,7-Dihydroxy-4-oxo-2-phenyl-4H-1-benzopyran-8-yl)oxy]methyl]-N-[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]-1H-1,2,3-triazole-1-octanamide

Melting Point

178-179°C

Density

1.52±0.1 g/cm3 (Predicted)

InChI Key

MRRHEHIWXXJQQL-UHFFFAOYSA-N

InChI

InChI=1S/C39H36N6O10/c46-27-18-29(48)35(36-34(27)28(47)19-30(55-36)22-10-5-4-6-11-22)54-21-23-20-44(43-42-23)17-8-3-1-2-7-14-31(49)40-25-13-9-12-24-33(25)39(53)45(38(24)52)26-15-16-32(50)41-37(26)51/h4-6,9-13,18-20,26,46,48H,1-3,7-8,14-17,21H2,(H,40,49)(H,41,50,51)

SMILES

C1CC(=O)NC(=O)C1N2C(=O)C3=C(C2=O)C(=CC=C3)NC(=O)CCCCCCCN4C=C(N=N4)COC5=C(C=C(C6=C5OC(=CC6=O)C7=CC=CC=C7)O)O

Mechanism

Target: Targets CDK9 cyclin-dependent kinase for experimental targeted protein degradation studies.

Binding Site: Binds the CDK9 ATP-binding pocket and cereblon thalidomide-binding domain to support productive ternary complex formation.

Mechanism of Action: PROTAC CDK9 degrader-2 is designed for use in PROTAC or targeted protein degradation experiments directed toward CDK9 cyclin-dependent kinase. 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 CDK9 Degradation: This product enables the targeted degradation of cyclin-dependent kinase 9 (CDK9), a critical regulator of transcriptional elongation. By facilitating the selective removal of CDK9, researchers can explore its role in transcriptional regulation and investigate potential therapeutic interventions in diseases characterized by dysregulated transcription.

• Targeted Protein Degradation in Cancer Research: PROTAC CDK9 degrader-2 provides a powerful tool for studying the implications of CDK9 degradation in cancer cells. Researchers can utilize this degrader to dissect the pathways involved in oncogenesis and assess the therapeutic potential of targeting CDK9 in various malignancies.

• Transcriptional Regulation Studies: Utilizing this degrader, scientists can specifically degrade CDK9 to study its impact on transcriptional processes. This approach allows for the dissection of CDK9’s role in gene expression regulation, offering insights into the fundamental mechanisms of transcriptional control.

• Investigating CDK9-Dependent Pathways: The targeted degradation of CDK9 using PROTAC technology provides a unique opportunity to examine CDK9-dependent signaling pathways. Researchers can leverage this tool to understand the broader implications of CDK9 activity in cellular homeostasis and its contribution to disease pathogenesis.

1. Discovery of Wogonin-based PROTACs against CDK9 and capable of achieving antitumor activity.

Bian, J., Ren, J., Li, Y., Wang, J., Xu, X., Feng, Y., Tang, H., Wang, Y. and Li, Z., 2018. Bioorganic chemistry, 81, pp.373-381.

Wogonin is a natural product isolated from the Scutellaria baicalensis and has been proved to be a potent and selective inhibitor of CDK9. Using this scaffold, we designed and synthesized a series of proteolysis targeting chimeras (PROTACs) targeting CDK9 by recruiting ubiquitin E3 ligase cereblon (CRBN). For constructing diverse Wogonin-based PROTACs, a "click chemistry" approach was employed for the synthesis of CDK9-targeting PROTACs. The results of western blotting assays showed that compounds containing triazole group in the linker could selectively downregulate the intracellular CDK9 level. Among these compounds, 11c could selectively degrade CDK9 in a concentration-dependent manner. In addition, the application of the proteasome inhibitor MG132 and CRBN siRNA silencing confirmed that 11c could promote the proteasome-dependent and CRBN-dependent degradation. Consistent with the degradation of the CDK9 protein, 11c selectively inhibits proliferation of CDK9-overexpressed cancer cells. Thus, our Wogonin-based PROTAC would be an efficient probe that induces the degradation of CDK9.

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