Hit expansion

Chemical modification of an original hit obtained from screening to generate a suite of related derivatives.

Although a hit has been found to have antibacterial activity, it may be a weak inhibitor or have other properties unfavourable to drug development. Chemical modifications may improve antibacterial activity or another important property such as solubility.

Importantly, work on a family of related compounds can reveal which parts of the compound are most important to its antibacterial activity (structure-activity relationship). This information can guide further chemical modification to enhance its activity and specificity.

Discovery and preclinical development of new antibiotics (Upsala Journal of Medical Sciences, 2014)