Small Molecule Ligands Screening

Many biological molecules interact with small molecules, such as cofactors, metabolites, or drugs, which collectively defines as “ligands”. Small molecule ligands not only participate in basic enzymatic reactions to build metabolic networks, but also act as extra and intra cellular signals to participate in signal regulation networks. Thus, screening of small molecule ligands for affinity and activity against a protein target is vital in drug development.

Here we describe two available methods for small molecule ligands screening, high-throughput screening (HTS) and virtual screening (VS).

High-throughput screening (HTS)

HTS is a technique for running millions of biological or chemical tests against a specific drug target, cell or organism in a short time based on robotics, liquid handling, plate reader detection. This method is extensively used in pharmaceutical industry for quickly testing the activity of molecules (like small molecule ligands). A critical feature of HST is the generation of amount data, therefore dedicated data analysis and management platforms is indispensable. Our automation platform is fully integrated with industry leading informatics to ensure data fidelity and compound tracking, providing a full audit trail for data, samples and operations.

Figure 1. The process of HTS.

Virtual screening (VS)

VS is a computer aided method that could save time and costs, reduce failure rate in drug development process, show success in predicting new leads with good hit rates reported. Profacgen provides VS services with E3 ligase or target protein. To date, the most popular E3 ligases for small molecule ligands screening include the Von Hippel-Lindau disease tumor suppressor protein (VHL), the Mouse Double Minute 2 homologue (MDM2), the Cellular Inhibitor of Apoptosis (cIAP) and ereblon (CRBN).

Figure 2. VS process.

Profacgen takes advantage of the most state-of-the-art techniques and software tools for small molecule ligands screening. Our optimized protocol provides the likelihood to find more innovative hits in a faster and costless manner. Moreover, we promise to work closely with customers, please feel free to contact us for a detailed quotation.

References:

1. Lee JH, Park S, Hyun H, Bordo MW, Oketokoun R, Nasr KA, Frangioni J, Choi HS. (2013). High-throughput screening of small molecule ligands targeted to live bacteria surface. Analytical Chemistry, 85(7), 3508–3514. doi:10.1021/ac303199x
2. Sousa SF, Cerqueira NMFSA, Fernandes PA, Ramos MJ. (2010). Virtual Screening in drug design and development. Combinatorial Chemistry & High Throughput Screening, 13(5), 442–453. doi:10.2174/138620710791293001