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In the past decade, fragment based drug design (FBDD) has risen as a new and effective approach to identify lead compounds and continues to show great promise in drug discovery. It requires the use of sensitive techniques such as X-ray crystallography to identify hits among low molecular weight fragment compounds that have a weak binding affinity to a drug target. The hit fragments could be then structurally optimized to lead compounds with high affinity and specificity.
Majority of biological processes would not be possible without protein–protein interactions (PPIs). Human interactome is estimated to comprise more than 600,000 PPIs, and only a small part of them has been studied. PPIs are associated with a growing number of diseases and have garnered significant interest in pharmaceutical research offering attractive opportunities for therapeutic intervention. Designing molecules that interfere with the formation of protein complexes is one of the recent challenges in drug design.
Bromodomains are acetyl-lysine recognition modules of a diverse group of proteins that play crucial role in chromatin organization and regulation of gene transcription. Proteins that contain bromodomains have been involved in the development of a large variety of diseases. Bromodomain and extra-terminal (BET) proteins, which belong to a class of proteins collectively called epigenetic “readers”, have recently emerged as prospective drug targets for treatment of cancers, inflammatory diseases, and other medical conditions.
Retinoic acid receptor-related orphan receptors (RORs) alpha, beta, and gamma play critical roles in a variety of physiological processes, which include regulation of metabolism, development and immunity as well as the circadian rhythm. Several reports have presented evidence for a potential role of RORs in pathologies such as osteoporosis, several autoimmune diseases, asthma, cancer, and obesity. This stimulated the development of RORs synthetic ligands and opened up the possibility of chemotherapeutic intervention for these receptors.