Hit Identification

Hit Identification

The entry point for chemistry program within drug discovery research is generally the identification of molecules of high specificity with an adequate activity in a suitable target assay. Such initial hits can be generated in a number of ways. It is therefore important to employ alternative hit-identification strategies that are able to tackle a variety of biological macromolecular targets effectively, and to identify proprietary, synthetically tractable and pharmacologically relevant compounds rapidly. These methods can be subdivided into those that require very detailed ligand and/or target information, and those that do not. The former include techniques such as nuclear magnetic resonance (NMR) and X-ray crystallography. Those strategies that do not require any prior information on target or ligand are using serendipity-based search strategies in either a given physical or virtual compound subset. Examples of random hit-identification strategies can be included by biophysical and biochemical testing that generally employ the method of detecting a molecular-binding event, usually in a high-throughput screening (HTS).

BOC Sciences provides varieties of methods including NMR, X-ray crystallography and HTS for hit identification.


NMR is a physical phenomenon, and by studying the peaks of NMR spectra, the structure of compounds can be determined. It can be a very selective technique to distinguish atoms in a molecule or molecules of the same type according to their local chemical conditions. As a useful tool in the hit identification, NMR spectroscopy techniques have been widely applied to detect ligand binding and monitor enzyme kinetics and inhibition. For example, methods for detecting binding by NMR fall into two main categories: those monitoring NMR signals from the protein, such as protein chemical-shift perturbation studies, and those monitoring the ligand, which exploits the large differences in the rates of rotational and translational motions of a small molecule in the free state relative to when it is bound to a macromolecule. A common protein-based approach is to label the target receptor with stable isotopes such as 15N and/or 13C. Binding of a ligand or a macromolecule alters the chemical environment around the binding site, which will perturb the chemical shift of magnetic nuclei at this site.

X-ray crystallography is a technique developed to analyze the atomic and molecular structures of crystals by determining the X-rays caused by the crystalline atoms. By measuring the angle and the intensity of these beams, a three-dimensional picture of the electron density within a crystal is given. For example, protein X-ray crystallography can be applied to the rationalization of the fragment-binding mode in the ATP binding site of Hsp90, which is an important member of a class of proteins known as molecular chaperones. This structural information is then used to evolve the fragments to hits, either by growing the fragment or combining structural features from a lot of compounds.

HTS is a scientific method widely used in drug discovery, which can help identify hits, antibodies, or genes that regulate a specific biological pathway. The results of HTS will provide identification of hit as a starting point for drug design and an understanding of the interactions or roles in specific biochemical processes in drug discovery.

BOC Sciences has a series of methods that can provide high-quality and effective hit compounds for your drug discovery. We would like to hear from you and look forward to cooperating with you.


  1. Napolitano, C. (2009) “DESIGN AND SYNTHESIS OF NOVEL SCAFFOLDS AND BUILDING BLOCKS (Doctoral dissertation, Università degli studi di Ferrara)’.

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