Compound Libraries

Compound Libraries

Compound libraries are widely used in target identification, high-throughput/focused screening for new hits that might be developed into a drug, drug repositioning/repurposing, predictive toxicology, or new target discovery through the integration of small-molecule chemogenomics with genetic approaches, such as RNA-mediated interference and CRISPR/Cas9.

Depending upon their scope (specific goal or diverse oriented goal) and design (chemical space or scaffold), the compound libraries developed by our partner TargetMol can be classified as Focused Bioactive Libraries, Natural Product Libraries, Fragment Libraries, and Diversity Sets, see below. These libraries have been extensively validated in their in-house biological assays and widely employed by research institutions and pharmaceutical companies in complementary screening strategies. Identifying novel and robust chemical starting points remains one of the biggest challenges in drug discovery today. Over the last decade, it has been common practice during the early stage of a project to screen vast numbers of compounds that cover larger section of chemical space evenly (diversity-led paradigm) in high-throughput assays in order to identify those chemicals which have the potential to modulate the target of interest. The costly nature of such mass screening, the consequent need to use reductionist assays that are optimized primarily for scale and speed, and the increasing realization that drug property space is far from random has more recently led to the use of smaller, higher quality screening collections (target-led approaches). All of these compound libraries and their screening approaches have their own particular advantages and disadvantages.

Focused Bioactive Libraries

Generally higher hit rates are observed in screening focused bioactive libraries when compared with the screening of diverse sets, and the hit clusters obtained from a successful focused library screening campaign usually exhibit discernable structure-activity relationships that facilitate follow up of these hits. Focused Bioactive Libraries is a powerful tool for drug screening, cell induction, drug repurposing, mechanism research, target identification, positive control and other related research fields. FDA-approved drug libraries as well as Anti-COVID-19/SARS-CoV-2 libraries are offered.

Natural Product Libraries

Natural products are an unsurpassed source of chemical diversity and an ideal starting point for any screening program for pharmacologically active small molecules. Historically, natural products have been the most successful source of new drugs. Natural Product Libraries is a powerful tool for cell induction research and the drug screening focused on unique natural structures along with new bioactivity.

Fragment Libraries

Fragment-based drug discovery (FBDD) has emerged in the past decade as an alternative approach to traditional lead identification via high-throughput screening (HTS). Unlike HTS, FBDD identifies smaller compounds, the “fragments,” which bind to different parts of a biological target. FBDD has played a role in discovery of 2 approved drugs (Vemurafenib and Venetoclax) and at least 30 drugs that are in various stages of clinical development. In response to this evident trend in drug discovery, TargetMol has designed its Fragment Libraries, including a selection of unique fragment subsets: Drug-Fragment Library, High Solubility Fragment Library, and Featured Fragment Library.

Diversity Sets

In drug discovery high-throughput screening, it is desirable to screen a drug target against a selection of chemicals that try to take advantage of as much of the appropriate chemical space as possible. The wider the chemical space that is sampled by the chemical library, the better the chance that high-throughput screening will find a "hit"—a chemical with an appropriate interaction in a biological model that might be developed into a drug. The chemical space of all possible chemical structures is extraordinarily large. To balance the cost of screening many hundreds of thousands of inactive compounds in a large diverse compound library against the benefits such as directly establishing structure–activity relationships (SAR) from the screening data and increasing the chances of identifying a broad range of hit series, TargetMol has designed two diversity sets: Mini Scaffold Library and Golden Scaffold Library. Selected from 1.6 million drug-like compounds with only 1 compound (Mini Scaffold Library, 5033 compounds) or 1-3 compounds (Golden Scaffold Library, 10000 compounds) for each scaffold, these two compound libraries can decrease the cost of screening and lower the screening threshold for single project team without compromise in losing sufficient information. In this case the initial screen will need to be followed by further rounds of purchase of compound analogues and screening to validate and expand the SAR around the hits.

you need any help?

Please contact:

Dr. Bettina Buchmann

Tel. +49 (0) 6221 71415 16 info@biocat.com