Inhibitors for BRD-4

Project information

  • Publication: In silico study directed towards identification of novel high-affinity inhibitors targeting an oncogenic protein: BRD4-BD1, Tumdam, R., Kumar, A., Subbarao, N. and Balaji B.S., SAR QSAR Environ. Res., 2018, 29, 975-996

Cancer is one of the leading causes of human mortality. Development of small-molecule inhibitors targeted towards cancer-causing factors is expanding rapidly. In this research project, we have been focusing on targeting Bromodomain-containing protein 4 (BRD4) through in silico screening of a small-molecule chemical library against the acetyl–lysine binding site of the first bromodomain (BD1). Potential inhibitors identified through virtual screening were further studied through molecular dynamics simulations, water entrapment analysis and Molecular Mechanics (MM)/Poisson–Boltzmann surface area (PBSA) binding free energy calculations. Many of the identified compounds exhibit better G-score (–11.64 kcal∙mol-1 to –10.31 kcal∙mol-1) and predicted binding affinity (–9.66 kcal∙mol-1 to –6.63 kcal∙mol-1) values towards BRD4-BD1 than that of the reference compound (+)-JQ1. Of all the compounds screened we have identified NSC744713 shows better binding free energy.

Collaborator: Dr. N. Subbarao, School Of Computational and Integrative Sciences, Jawaharlal Nehru University, New Delhi, India.