Compound Libraries

A compound library or chemical library is a collection of stored chemicals usually used ultimately in high-throughput screening or industrial manufacture. Depending upon their scope (specific goal or diverse oriented goal) and design (chemical space or scaffold), our compound libraries can be classified as Focused Bioactive Libraries, Natural Product Libraries, Fragment Libraries, and Diversity Sets. These libraries have been extensively validated in our 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.

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, we 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.