Name: THAL SNS 032
Brand: BOC Sciences
Rating: 5 (1 reviews)

Size

Price

Stock

Quantity

$--

In stock

Purity

≥98%

ShelfLife

2 years

Storage

Store at -20°C

IUPACName

N-[5-[(5-tert-butyl-1,3-oxazol-2-yl)methylsulfanyl]-1,3-thiazol-2-yl]-1-[2-[2-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethoxy]ethylamino]-2-oxoethyl]piperidine-4-carboxamide

Synonyms

N-(5-(((5-(tert-butyl)oxazol-2-yl)methyl)thio)thiazol-2-yl)-1-(14-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)-2-oxo-6,9,12-trioxa-3-azatetradecyl)piperidine-4-carboxamide; 1-Piperidineacetamide, 4-[[[5-[[[5-(1,1-dimethylethyl)-2-oxazolyl]methyl]thio]-2-thiazolyl]amino]carbonyl]-N-[2-[2-[2-[2-[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]amino]ethoxy]ethoxy]ethoxy]ethyl]-; SNS-THAL-032; Thal-SNS-032; THAL-SNS-032

Density

1.40±0.1 g/cm3

InChI Key

BXDZOYLPNAIDOC-UHFFFAOYSA-N

InChI

InChI=1S/C40H52N8O10S2/c1-40(2,3)29-21-43-32(58-29)24-59-33-22-44-39(60-33)46-35(51)25-9-13-47(14-10-25)23-31(50)42-12-16-56-18-20-57-19-17-55-15-11-41-27-6-4-5-26-34(27)38(54)48(37(26)53)28-7-8-30(49)45-36(28)52/h4-6,21-22,25,28,41H,7-20,23-24H2,1-3H3,(H,42,50)(H,44,46,51)(H,45,49,52)

SMILES

CC(C)(C)C1=CN=C(O1)CSC2=CN=C(S2)NC(=O)C3CCN(CC3)CC(=O)NCCOCCOCCOCCNC4=CC=CC5=C4C(=O)N(C5=O)C6CCC(=O)NC6=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: THAL SNS 032 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-Driven Kinase Degradation: THAL SNS 032 is designed to facilitate the targeted degradation of specific kinases, offering a powerful tool for researchers investigating kinase-driven signaling pathways. By selectively degrading these proteins, researchers can elucidate their roles in cellular processes and disease mechanisms, advancing the understanding of kinase-related pathologies.

• Selective Protein Degradation: This PROTAC molecule provides a strategic approach to selectively degrade proteins of interest, enabling detailed studies of protein function and interaction networks. By utilizing THAL SNS 032, scientists can explore the dynamic proteome landscape and its implications in various biological contexts.

• Targeted Cancer Research: Employing THAL SNS 032 in cancer research allows for the exploration of targeted protein degradation as a therapeutic strategy. By degrading oncogenic proteins, researchers can investigate potential pathways for therapeutic intervention, contributing to the development of innovative cancer treatments.

• Functional Proteomics: THAL SNS 032 serves as a critical tool in functional proteomics, facilitating the study of protein turnover and stability. Through targeted degradation, researchers can analyze protein life cycles and their impact on cellular homeostasis, offering insights into the regulation of proteostasis.

1. Pharmacological perturbation of CDK9 using selective CDK9 inhibition or degradation.

Olson, C.M., Jiang, B., Erb, M.A., Liang, Y., Doctor, Z.M., Zhang, Z., Zhang, T., Kwiatkowski, N., Boukhali, M., Green, J.L. and Haas, W., 2018. Nature chemical biology, 14(2), pp.163-170.

Cyclin-dependent kinase 9 (CDK9), an important regulator of transcriptional elongation, is a promising target for cancer therapy, particularly for cancers driven by transcriptional dysregulation. We characterized NVP-2, a selective ATP-competitive CDK9 inhibitor, and THAL-SNS-032, a selective CDK9 degrader consisting of a CDK-binding SNS-032 ligand linked to a thalidomide derivative that binds the E3 ubiquitin ligase Cereblon (CRBN). To our surprise, THAL-SNS-032 induced rapid degradation of CDK9 without affecting the levels of other SNS-032 targets. Moreover, the transcriptional changes elicited by THAL-SNS-032 were more like those caused by NVP-2 than those induced by SNS-032. Notably, compound washout did not significantly reduce levels of THAL-SNS-032-induced apoptosis, suggesting that CDK9 degradation had prolonged cytotoxic effects compared with CDK9 inhibition. Thus, our findings suggest that thalidomide conjugation represents a promising strategy for converting multi-targeted inhibitors into selective degraders and reveal that kinase degradation can induce distinct pharmacological effects compared with inhibition.

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