Chemical compounds

Chemical compounds

To begin with, chemical compounds, as you may already know, are molecules consisting of two or more different chemical elements. As it can be understood from the definition, nearly everything, living and non-living, contains numerous chemical compounds. Moreover, more and more new compounds are synthesized by researchers to be added to an existing diversity of molecules.

The main goal for development of new compounds is the search for novel drugs to be used in treatment of a variety of diseases - from cancer to allergies. ChemDiv’s stock of chemical compounds provides 1.6 million distinct compounds for multiple target proteins as well as the 75K building blocks database. Since its foundation 30 years ago, the company has been able to put together unique compound collections sold all over the world. Let’s take a closer look at ChemDiv’s stock of compounds and opportunities of its application.

Annotated libraries

Let us begin with a brief history of biological annotation development. Annotated libraries of chemical compounds have their origins in 1988, when Evans and coworkers put forward the idea of forming bio oriented compound collections based on their high biological activity [1]. Compounds in the annotated library fall into three main categories - tools, probes, and drugs (Figure 1, [2]):

• Tools help to investigate molecular mechanisms behind biological processes. They are sometimes non-selective and are commonly used in construction of specific assays. An example of tool chemical compound is forskolin (Figure 1, [2]), which is used in G-protein coupled receptor (GPCR) studies to increase the basal cAMP, which in turn creates an assay window for ligand detection.

• Probes, on the other hand, are designed to regulate specific pathways and/or proteins. An ideal probe chemical compound has high affinity, stability, efficacy and selectivity. Probes such as MEK1/2 inhibitor PD0325901 (Figure 1, [2]) bind to the allosteric site of the specific target instead of the orthosteric site, which results in higher selectivity even among the same class of protein kinases.

• Drugs are the last but not the least category of annotated library compounds. Because of the potential of their applications, drugs are subject to strict requirements: they must have low toxicity, high bioavailability and so on. There are plenty of examples of FDA-approved drugs, and ChemDiv offers a library containing analogues of them.

Figure 1. Different kinds of compounds in annotated libraries [2].

ChemDiv’s chemical database provides 17 annotated libraries, including antiviral collection, human GPCR annotated collection, CNS target protein annotated collection, etc. Each collection contains information about target proteins, chemical compounds from the stock and annotated target activity.

Diversity libraries

The successful screening of chemical compound libraries as a part of the drug development process depends directly on various factors, including size of the stock, its quality, and, of course, diversity of the stock. Diversity of chemical compounds provides knowledge of how well the amount of possible compound variants (or so-called chemical space) is covered.

Compound diversity can be achieved by varying several structural and physico-chemical properties of molecules. Analysis of molecular scaffolds (core structure of a molecule with preferable bioactive properties) is used to conduct measurements of diversity. Another widespread approach to diversity measurement is molecular fingerprints, particularly useful in calculating similarity coefficients such as Tanimoto coefficient [3].

ChemDiv’s diversity libraries cover the chemical space of millions of chemical compounds. Diversity in collections is provided by numerous parameters (Figure 2): 3D shape of the molecule, pharmacophore diversity, difference in molecular scaffolds, physico-chemical properties, etc.

Figure 2. ChemDiv’s 3D-Diversity Natural-Product-Like Library compound selection pipeline

Focused libraries

Focused, or targeted, chemical compound collections are required if a certain biological process under study has a protein proven as potential molecular target (or a group of proven molecular targets with similar properties). Target protein is chosen on the basis of the well-studied molecular mechanisms. Such a target does usually have a known native structure, which allows researchers to use computational methods for selection of possible ligands to be linked to the binding site of the protein.

In the absence of information about structural properties of the target there are alternative methods of focused libraries selection. First of them relies on the predictions of the protein’s binding site structural properties made from amino acid sequence. Second alternative approach uses known ligands of the protein to construct and choose molecules with similar molecular scaffolds [4].

ChemDiv offers over 100 predesigned focused libraries for specific targets and families of targets. Those include ion channels, GPCR, proteases, coronavirus and numerous other interesting targets for research. The focused libraries are formed on the basis of the modern pharmaceutical industry needs via analysis of the newest biological and chemical articles, target determination, search for molecular scaffolds of potential ligands both in silico and in vitro. In addition to that, ChemDiv provides custom focused library selection on request.

Summary

ChemDiv has a large chemical database of compounds and predesigned libraries of chemical compounds meeting a diverse variety of customer requests. ChemDiv’s research team follows current trends in today’s drug discovery, which allows to update the chemical database of libraries regularly based on the needs of modern science. Besides pre-preparation of libraries, the company gives a unique opportunity to customize your own library based on the inquiry as well as purchase an existing predesigned collection.

References

1. Evans BE, Rittle KE, Bock MG, et al. “Methods for drug discovery: development of potent, selective, orally effective cholecystokinin antagonists”. J Med Chem. 1988;31(12):2235-2246.

2. Wassermann AM, Camargo LM, Auld DS. “Composition and applications of focus libraries to phenotypic assays”. Front Pharmacol. 2014;5:164. Published 2014 Jul 24.

3. Saldívar-González FI, Huerta-García CS, Medina-Franco JL. “Chemoinformatics-based enumeration of chemical libraries: a tutorial”. J Cheminform. 2020;12(1):64. Published 2020 Oct 27.

4. Harris CJ, Hill RD, Sheppard DW, Slater MJ, Stouten PF. “The design and application of target-focused compound libraries”. Comb Chem High Throughput Screen. 2011;14(6):521-531.