Name: TL 12-186
Brand: BOC Sciences
Rating: 5 (1 reviews)

Size

Price

Stock

Quantity

$--

In stock

Purity

≥98%

Solubility

Soluble in DMSO

Appearance

Yellow Solid

ShelfLife

2 years

Storage

Store at -20°C

IUPACName

N-[2-[2-[2-[4-[4-[[5-chloro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]phenyl]piperazin-1-yl]ethoxy]ethoxy]ethyl]-2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]acetamide

Synonyms

N-(2-(2-(2-(4-(4-((5-chloro-4-((2-(isopropylsulfonyl)phenyl)amino)pyrimidin-2-yl)amino)phenyl)piperazin-1-yl)ethoxy)ethoxy)ethyl)-2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)acetamide; Acetamide, N-[2-[2-[2-[4-[4-[[5-chloro-4-[[2-[(1-methylethyl)sulfonyl]phenyl]amino]-2-pyrimidinyl]amino]phenyl]-1-piperazinyl]ethoxy]ethoxy]ethyl]-2-[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]amino]-; N-[2-[2-[2-[4-[4-[[5-Chloro-4-[[2-[(1-methylethyl)sulfonyl]phenyl]amino]-2-pyrimidinyl]amino]phenyl]-1-piperazinyl]ethoxy]ethoxy]ethyl]-2-[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]amino]acetamide; TL12-186

Density

1.411±0.06 g/cm3

InChI Key

YNGWQHGVASHCBK-UHFFFAOYSA-N

InChI

InChI=1S/C44H51ClN10O9S/c1-28(2)65(61,62)36-9-4-3-7-33(36)50-40-32(45)26-48-44(52-40)49-29-10-12-30(13-11-29)54-19-17-53(18-20-54)21-23-64-25-24-63-22-16-46-38(57)27-47-34-8-5-6-31-39(34)43(60)55(42(31)59)35-14-15-37(56)51-41(35)58/h3-13,26,28,35,47H,14-25,27H2,1-2H3,(H,46,57)(H,51,56,58)(H2,48,49,50,52)

SMILES

CC(C)S(=O)(=O)C1=CC=CC=C1NC2=NC(=NC=C2Cl)NC3=CC=C(C=C3)N4CCN(CC4)CCOCCOCCNC(=O)CNC5=CC=CC6=C5C(=O)N(C6=O)C7CCC(=O)NC7=O

Mechanism

Target: Targets pan-kinase degradation targets selected through promiscuous kinase-ligand engagement for experimental targeted protein degradation studies.

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

Mechanism of Action: TL 12-186 is designed for use in PROTAC or targeted protein degradation experiments directed toward pan-kinase degradation targets selected through promiscuous kinase-ligand engagement. 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: TL 12-186 is designed for the targeted degradation of kinases, offering researchers a powerful tool to study kinase signaling pathways. By selectively degrading specific kinases, this PROTAC facilitates the investigation of their roles in cellular processes and disease mechanisms.

• Targeted Degradation of Oncoproteins: Utilize TL 12-186 to selectively degrade oncoproteins, providing insights into cancer biology and potential therapeutic targets. This application enables the exploration of oncoprotein function and the consequences of their degradation on tumor cell viability and proliferation.

• Epigenetic Regulator Degradation via PROTAC: TL 12-186 can be employed to degrade epigenetic regulators, offering a unique approach to study their impact on gene expression and chromatin dynamics. This facilitates the understanding of epigenetic modifications in various biological contexts and disease states.

• Investigating Protein-Protein Interactions: Leverage TL 12-186 to dissect protein-protein interactions by degrading one component of the complex. This strategy aids in elucidating the functional significance of these interactions and their roles in cellular signaling networks.

1. 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.

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* 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