dBRD9 Chemical Properties

Boiling point:

1014.2±65.0 °C(Predicted)

Density 

1.357±0.06 g/cm3(Predicted)

pka

10.74±0.40(Predicted)

form 

Solid

color 

Light yellow to yellow

InChIKey

AIOCFZJGGGEWDK-UHFFFAOYSA-N

SMILES

O=C1N(C2CCC(=O)NC2=O)C(=O)C2=CC=CC(NCCOCCOCCNC(=O)CN(C)CC3C(=CC(C4=CN(C)C(=O)C5=CN=CC=C45)=CC=3OC)OC)=C12

dBRD9 Usage And Synthesis

Description

dBRD9 is a potent and selective Degrader (PROTAC?) of BRD9 (IC50 = 56.6 nM in MOLM-13 cells). dBRD9 is composed of the BRD9 inhibitor BI 7273 conjugated to the cereblon E3 ligase ligand pomalidomide. Does not degrade BRD4 or BRD7 at concentrations up to 5 μM. Displays antiproliferative effects in human AML cell lines.

Biological Activity

dBRD9 is a PEG-linked pomalidomide conjugate and was found to prompt rapid BRD9 degradation over a broad range of concentrations. Besides, also shows an improved bromodomain engagement profile, with reduced binding activity across the BET family. Meanwhile, dBRD9 (0.5, 5, 50, 500, 5000 nM; 4 h) decreases the expression of BRD9 protein in MOLM-13 cells in a dose-dependent manner. However, it shows no significant effect on the expression of BRD4 and BRD7 proteins. Moreover, dBRD9 (100 nM; 2 h) shows selectivity for BRD9 degradation with a 5.5 median fold lower abundance in dBRD9 treated samples in MOLM-13 cells. However, the levels of other proteins were remarkably static between treatments, with 99% of proteins differing less than 0.30 fold. In addition, dBRD9 (0-100; 7 days) shows a potent anti-proliferative effect in EOL-1 and MOML-13 cells in a dose-dependent manner. All in all, dBRD9 is a PROTAC and can selectively degrade BRD9.