Name: PROTAC Mcl1 degrader-1
Brand: BOC Sciences
Rating: 5 (1 reviews)

Size

Price

Stock

Quantity

$--

In stock

Purity

≥98%

Solubility

Soluble in DMSO (50 mg/mL, Need ultrasonic)

Storage

Store at -20°C

IUPACName

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

Synonyms

Hexanediamide, N1-[2-[6-[(4-bromophenyl)thio]-1,3-dioxo-1H-benz[de]isoquinolin-2(3H)-yl]ethyl]-N6-[6-[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]amino]hexyl]-; N1-[2-[6-[(4-Bromophenyl)thio]-1,3-dioxo-1H-benz[de]isoquinolin-2(3H)-yl]ethyl]-N6-[6-[[2-(2,6-dioxo-3-piperidinyl)-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]amino]hexyl]hexanediamide; N1-(2-(6-((4-Bromophenyl)thio)-1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)ethyl)-N6-(6-((2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-4-yl)amino)hexyl)adipamide; Mcl-1 Degrader C3

Boiling Point

1146.5±65.0°C at 760 mmHg

Density

1.52±0.1 g/cm3

InChI Key

BORXNUWYWZOREQ-UHFFFAOYSA-N

InChI

InChI=1S/C45H45BrN6O8S/c46-27-15-17-28(18-16-27)61-35-21-19-32-39-29(35)9-7-10-30(39)42(57)51(43(32)58)26-25-49-37(54)14-4-3-13-36(53)48-24-6-2-1-5-23-47-33-12-8-11-31-40(33)45(60)52(44(31)59)34-20-22-38(55)50-41(34)56/h7-12,15-19,21,34,47H,1-6,13-14,20,22-26H2,(H,48,53)(H,49,54)(H,50,55,56)

SMILES

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

Mechanism

Target: Targets MCL1 anti-apoptotic BCL-2 family protein for experimental targeted protein degradation studies.

Binding Site: Binds the MCL1 BH3-binding groove and recruited E3 ligase ligand site to support productive ternary complex formation.

Mechanism of Action: PROTAC Mcl1 degrader-1 is designed for use in PROTAC or targeted protein degradation experiments directed toward MCL1 anti-apoptotic BCL-2 family protein. 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 Mcl1 Degradation: PROTAC Mcl1 degrader-1 is designed to selectively target and degrade the Mcl1 protein, a member of the Bcl-2 family involved in apoptosis regulation. This application enables researchers to study the role of Mcl1 in cancer cell survival and investigate potential therapeutic strategies for Mcl1-dependent malignancies.

• Targeted Protein Degradation in Cancer Research: By harnessing the power of PROTAC technology, PROTAC Mcl1 degrader-1 facilitates the degradation of Mcl1, providing a valuable tool for understanding its contribution to tumorigenesis. This application supports the exploration of Mcl1 as a target for developing novel anti-cancer therapies.

• Mechanistic Studies of Apoptosis: Utilizing PROTAC Mcl1 degrader-1 allows scientists to dissect the mechanistic pathways of apoptosis by specifically degrading Mcl1. This application aids in elucidating the complex interactions between pro-apoptotic and anti-apoptotic proteins, offering insights into cell death regulation.

• Drug Resistance Investigation: PROTAC Mcl1 degrader-1 serves as a powerful research tool for investigating mechanisms of drug resistance in cancer. By enabling targeted degradation of Mcl1, researchers can explore how its modulation affects the sensitivity of cancer cells to chemotherapy and other 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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