Name: PROTAC Bcl2 degrader-1
Brand: BOC Sciences
Rating: 5 (1 reviews)

Size

Price

Stock

Quantity

$--

In stock

Purity

≥98%

Solubility

Soluble in DMSO (25 mg/mL, 26.54 mM, Need ultrasonic)

Storage

Store at -20°C, stored under nitrogen

IUPACName

N-[2-[6-(4-bromophenyl)sulfanyl-1,3-dioxobenzo[de]isoquinolin-2-yl]ethyl]-N'-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]ethoxy]ethoxy]ethyl]hexanediamide

Synonyms

Hexanediamide, N1-[2-[6-[(4-bromophenyl)thio]-1,3-dioxo-1H-benz[de]isoquinolin-2(3H)-yl]ethyl]-N6-[2-[2-[2-[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]amino]ethoxy]ethoxy]ethyl]-; BCL2 Degrader C5; N1-(2-(6-((4-Bromophenyl)thio)-1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)ethyl)-N6-(2-(2-(2-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)ethoxy)ethoxy)ethyl)adipamide; N-(2-{6-[(4-Bromophenyl)sulfanyl]-1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl}ethyl)-N'-{2-[2-(2-{[2-(2,6-dioxo-3-piperidinyl)-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl]amino}ethoxy)ethoxy]ethyl}hexanediamide

Boiling Point

1158.2±65.0°C (Predicted)

Density

1.54±0.1 g/cm3 (Predicted)

InChI Key

IUSLKFLLLNNOGR-UHFFFAOYSA-N

InChI

InChI=1S/C45H45BrN6O10S/c46-27-11-13-28(14-12-27)63-35-17-15-32-39-29(35)5-3-6-30(39)42(57)51(43(32)58)22-19-48-36(53)9-1-2-10-37(54)49-21-24-62-26-25-61-23-20-47-33-8-4-7-31-40(33)45(60)52(44(31)59)34-16-18-38(55)50-41(34)56/h3-8,11-15,17,34,47H,1-2,9-10,16,18-26H2,(H,48,53)(H,49,54)(H,50,55,56)

SMILES

C1CC(=O)NC(=O)C1N2C(=O)C3=C(C2=O)C(=CC=C3)NCCOCCOCCNC(=O)CCCCC(=O)NCCN4C(=O)C5=C6C(=C(C=C5)SC7=CC=C(C=C7)Br)C=CC=C6C4=O

Mechanism

Target: Targets BCL-XL and related anti-apoptotic BCL-2 family proteins for experimental targeted protein degradation studies.

Binding Site: Binds the BCL-family BH3-binding groove and recruited E3 ligase ligand site to support productive ternary complex formation.

Mechanism of Action: PROTAC Bcl2 degrader-1 is designed for use in PROTAC or targeted protein degradation experiments directed toward BCL-XL and related anti-apoptotic BCL-2 family proteins. The bifunctional molecule links a target-recognition element to VHL, 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 Bcl2 Degradation: This product facilitates the selective degradation of the Bcl2 protein, a key regulator of apoptosis, using the PROTAC mechanism. Researchers can utilize this tool to investigate the role of Bcl2 in cancer cell survival and to explore potential therapeutic strategies for targeting Bcl2 in oncological studies.

• Targeted Protein Degradation in Apoptosis Research: By employing PROTAC Bcl2 degrader-1, scientists can effectively degrade Bcl2, enabling the study of apoptosis pathways. This application is crucial for understanding how Bcl2 modulates cell death and for identifying novel approaches to manipulate apoptotic mechanisms in various disease models.

• PROTAC-Based Functional Genomics: Use this degrader in functional genomics studies to dissect the biological functions of Bcl2. By achieving precise protein knockdown, researchers can elucidate Bcl2's involvement in cellular processes, providing insights into its role in disease pathogenesis and potential as a therapeutic target.

• Investigating Resistance Mechanisms: PROTAC Bcl2 degrader-1 allows for the exploration of resistance mechanisms to Bcl2 inhibition. Researchers can study how cells adapt to Bcl2 degradation, offering valuable data for developing strategies to overcome resistance in cancer treatments.

1. Proteolysis targeting chimeras for the selective degradation of Mcl-1/Bcl-2 derived from nonselective target binding ligands.

Wang, Z., He, N., Guo, Z., Niu, C., Song, T., Guo, Y., Cao, K., Wang, A., Zhu, J., Zhang, X. and Zhang, Z., 2019. Journal of Medicinal Chemistry, 62(17), pp.8152-8163.

Proteolysis targeting chimera (PROTAC) recruits an E3 ligase to a target protein to induce its ubiquitination and subsequent degradation. We reported success in the development of two PROTACs (C3 and C5) that potently and selectively induce the degradation of Mcl-1 and Bcl-2 (DC50 = 0.7 and 3.0 μM), respectively, by introducing the E3 ligase cereblon-binding ligand pomalidomide to Mcl-1/Bcl-2 dual inhibitors S1-6 and Nap-1 with micromolar-range affinity. C3-induced Mcl-1 ubiquitination translated into much more lethality in Mcl-1-dependent H23 cells than the most potent Mcl-1 occupancy-based inhibitor A-1210477 with nanomolar-range affinity. Moreover, structure-activity relationship analysis and molecular dynamic simulations discovered the structural basis for turning nonselective or promiscuous Bcl-2 family ligands into selective PROTACs. C3 and C5 exhibited reversible depletion in living cells, which provides a new potent toolkit for gain-of-function studies to probe the dynamic roles of Bcl-2 and Mcl-1 in apoptosis networks.

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