PROTAC Bcl2 degrader-1

Size	Price	Stock	Quantity
--	$--	In stock

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)

Canonical 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

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