Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5942_Библиотеки_им_академика_М_И_Перельмана

Before these online databases were established, the life of scientists was character­ized by time-consuming research in bound data collections. For chemists who were preparing a research project or a doctoral thesis, it meant disappearing into libraries for several days to evaluate the current state of knowledge and dening this as the starting point for their scientic work. The best-known data collections were the Gmelin for inorganic chemistry and the Beilstein for organic chemistry, in which structured research was possible [1, 2]. Chemical Abstracts (CA) was also available across disciplines, provided by the Chemical Abstracts Service (CAS), a subdivision of the American Chemical Society (ACS) established in 1907. The aim was to bring together and index all chemistry-related information (journals, books, patents, dis­sertations, congresses, etc.) in order to make them available [3, 4].

production, manufacturing organizations (CDMOs), in- or out-licensing, outsourc­ing, oshoring, company takeovers, etc.) must be assessed.

An analog database for 3D structures of nucleic acids is the Nucleic Acid Database (NDB), founded in 1992, in which sequences, structures, and functions can be searched freely (http://ndbserver.rutgers.edu/ (accessed 24 April 2022)) [9].

The development of a new database with additional information on sequences, functions, and interactions of nucleic acids was described in 2018 through a col­laboration between Rutgers University NDB and Bowling Green State University (RNAhub services). The NDB is to be replaced under the name Nucleic Acid Knowl­edge Base (NAKB) [10].

After a successful target validation, it is necessary to establish an appropriate assay in order to test a large number of compounds in a high-throughput process (high-throughput screening, HTS) with the aim of identifying biologically active substances (hit-nding).

Pharos (https://pharos.nih.gov/ (accessed 25 April 2022)) is a National Institutes of Health (NIH) sponsored Knowledge Management Center (KMC) database for Illuminating the Druggable Genome (IDG). It includes 20,412 targets, information on 13,704 diseases, and 339,220 ligands [20].

The results of an HTS run are the basis for further procedure in the projects. A precise analysis of the found active molecules (hits) such as structure, compound class, and patent status is important in order to develop lead structures. The aim of lead structure optimization is to improve the pharmacological, pharmacokinetic, and toxicological properties in order to avoid the risk of possible side eects and to improve bioavailability.

The most common reason for the occurrence of side eects is the insucient drug metabolism, the pharmacokinetic prole (DMPK), and the formation of reac­tive metabolites [22]. When creating a DMPK prole, absorption, the stability and structure of formed metabolites, and inhibition or activation of cytochrome peroxi­dase P450 (CYP) are taken into account [23]. Furthermore, the metabolic enzymes sulfotransferases (SULTs) and UDP-glucuronosyltransferase (UGT) play an impor­tant role in the in vivo degradation of drugs. Data and information on the enzymes, metabolites involved, and their biological and toxicological data can be found in sev­eral Open-Access databases.

The Human Metabolome Database (HMDB) (https://hmdb.ca/ (accessed 25 April

2022)) was established by the Human Metabolome Project and is funded by Genome Canada [24]. HMBD contains 220,945 entries for chemical, biological, biochemi­cal, and molecular biology data and also 8610 enzyme and transporter sequences.

2022)) ist ein Archiv zu humanen metabolischen Signalwegen, menschlichen Metaboliten und dem menschlichen Genom [26].

When developing an active ingredient, the toxicological properties must also be considered. A substance can have toxic eects, but there is also the possibility that toxic metabolites are formed [31, 32].