Kamada, Yusuke; Sakai, Nozomu; Sogabe, Satoshi; Ida, Koh; Oki, Hideyuki; Sakamoto, Kotaro; Lane, Weston; Snell, Gyorgy; Iida, Motoo; Imaeda, Yasuhiro; Sakamoto, Junichi; Matsui, Junji published the artcile< Discovery of a B-Cell Lymphoma 6 Protein-Protein Interaction Inhibitor by a Biophysics-Driven Fragment-Based Approach>, Safety of 4,5-Dichloropyrimidine, the main research area is drug screening lymphoma protein interaction inhibitor.
B-cell lymphoma 6 (BCL6) is a transcriptional factor that expresses in lymphocytes and regulates the differentiation and proliferation of lymphocytes. Therefore, BCL6 is a therapeutic target for autoimmune diseases and cancer treatment. This report presents the discovery of BCL6-corepressor interaction inhibitors by using a biophysics-driven fragment-based approach. Using the surface plasmon resonance (SPR)-based fragment screening, we successfully identified fragment 1 (SPR KD = 1200 μM, ligand efficiency (LE) = 0.28), a competitive binder to the natural ligand BCoR peptide. Moreover, we elaborated 1 into the more potent compound 7 (SPR KD = 0.078 μM, LE = 0.37, cell-free protein-protein interaction (PPI) IC50 = 0.48 μM (ELISA), cellular PPI IC50 = 8.6 μM (M2H)) by a structure-based design and structural integration with a second high-throughput screening hit.
Journal of Medicinal Chemistry published new progress about Antitumor agents (potential). 6554-61-6 belongs to class pyrimidines, and the molecular formula is C4H2Cl2N2, Safety of 4,5-Dichloropyrimidine.
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia