Hit identification is the first step for a complete drug discovery project. During the process, the potential compounds, namely hits, are found to interacted with target and modifying its function. A hits step with high quality and quick speed makes faster progress in drug discovery project. CD BioSciences provides customized services to help you successful with your research. Our highly experienced team provides the best identification approaches including high-throughput screening, in silico virtual screening, fragment-based drug discovery and high-content screening.
High-throughput screening (HTS) is capable of automatically testing many chemical and/or biological compounds against a specific drug target, which is traditional lead-screening way. HTS is to find hits that specifically interacts with the target in the desired manner through compound library screening. The result of the HTS analysis is the first step for further processes in the drug discovery project.
CD BioSciences have various HTS compound libraries, including but not limited to, natural product libraries, target-specific libraries, disease-specific libraries, research area-specific libraries, FDA approved drug libraries, etc. It is worth mentioning that our high-throughput crystallography service supports the rapid determination of multiple target-ligand crystal structures and offers many new opportunities for lead discovery.
In silico virtual screening is a computational technique used to search libraries of small molecules in drug discovery, which identifies those structures most likely to bind to a drug target. The results of virtual screening help HTS more directional, the higher hit rate, and largely fewer costs.
CD BioSciences has computer-aided drug design (CADD) platform, which can use structure-based (SBVS) for drug discovery projects. It can be used to find structurally novel ligands and is the preferred approach when the three-dimensional (3D) structure of the target protein is known.
Fragment-based drug discovery (FBDD) is based on identifying small chemical fragments, which may bind only weakly to the biological target, and then growing them or combining them to produce a lead with a higher affinity. In the early phase of FBDD, molecular weights of around 200 Da can be screened in libraries, and millimolar affinities can be considered useful. There are many advantages of screening low molecular weight fragment, such as, more hydrophilic hits, higher ligand efficiency, fewer sterically blocking groups.
CD BioSciences offers fragment-to-lead solutions with extensive experience and expertise. We have rich specialized knowledge and advanced equipment in X-ray crystallography, NMR spectroscopy, surface plasmon resonance, bio-layer interferometry, isothermal titration calorimetry, thermal shift assay, mass spectrometry. In addition, we own rich libraries targeted FBDD and use fragment growth, fragment linking, and fragment merging strategies to optimize the preliminarily screened fragments to improve their biological activity and drug-like properties, making it a potential lead compound with higher affinity.
High-content screening (HCS) is a method that is used in biological research and drug discovery to identify substances such as small molecules, peptides, or RNAi that alter the phenotype of a cell in a desired manner. By quantitatively and dynamically monitoring the effects of compounds on cell phenotypes (such as cell morphology, cell viability, and fluorescence intensity), compounds that significantly alter disease status can be screened out. Compared with the screening at the molecular level, cell-based screening eliminates the need for purification of the target protein, making the environment of screening and the target conformation closer to the natural physiological state, meanwhile, those compounds that are cytotoxic and/or cannot penetrate the cell membrane can be rapidly excluded.
CD BioSciences provides several categories of HCS, including dual reporter assays, nuclear translocation, cytosol to plasma membrane translocation, genotoxicity screening, and morphology measurements like cell shape, morphology, and target distribution changes. The comprehensive HCS services help you complete your projects more successfully and quickly.