Mechanistic Analysis of Chemically Diverse Bromodomain-4 Inhibitors Using Balanced QSAR Analysis and Supported by X-ray Resolved Crystal Structures.

ABSTRACT: Bromodomain-4 (BRD-4) is a key enzyme in post-translational modifications, transcriptional activation, and many other cellular processes. Its inhibitors find their therapeutic usage in cancer, acute heart failure, and inflammation to name a few. In the present study, a dataset of 980 molecules with a significant diversity of structural scaffolds and composition was selected to develop a balanced QSAR model possessing high predictive capability and mechanistic interpretation. The model was built as per the OECD (Organisation for Economic Co-operation and Development) guidelines and fulfills the endorsed threshold values for different validation parameters (R²_tr = 0.76, Q²_LMO = 0.76, and R²_ex = 0.76). The present QSAR analysis

SUBMITTER: Zaki MEA 

PROVIDER: S-EPMC9231298 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature