Bromodomain-containing Protein 4 (BRD4) is a key chromatin organizer that binds to acetylated histone lysine residues and regulates gene activation through transcription factor recruitment, enhancer assembly, and pause release of the RNA polymerase II complex for transcription elongation. BRD4 was also reported as an atypical kinase that phosphorylates serine 2 (Ser2) at the carboxyl-terminal domain of RNA polymerase II and in such way regulates eukaryotic transcription.
BRD4has been recently validated as a new epigenetic drug target for cancer and inflammation.It was shown that BRD4 is involved in the development ofacute myeloid leukemia, multiple myeloma, Burkitt’s lymphoma, NUT midline carcinoma, colon cancer, and inflammatory disease. Therefore, small molecule inhibitors of BRD4 interactions hold promise as useful therapeutics for several human diseases.
Otava Ltd. has designed new receptor-based BRD4 Targeted Library containing 1,250 compounds. The library has been developed by docking of compounds from Otava’s Drug-like Green Collection in binding site ofBRD4 X-ray crystal structure (PDB ID: 4J0S).This recently published complex of BRD4 with inhibitor has high resolution 1.84 Å and provides an excellent basis for focused library preparation.
The compounds have been selected based on energy score, presence of hydrogen bonds with side chain of Asn140 (this H-bond is present in many complexes BRD4 with inhibitor) and visual inspection for favorable ligand position in the BRD4 binding site. The library comprises drug-like compounds only.
If your research is focused on the development of BRD4 inhibitors, thistargetedlibrary is a good choice to start with.