Compilation of in silico tools and in vitro assays to study ADME-Tox properties of drug candidates


López-Nieto Arespa, Blanca


The pharmaceutical industry is the business sector dedicated exclusively to the manufacture, distribution, marketing and also in the preparation of pharmaceutical products, which are used in the treatment of various pathologies, as well as their prevention. The drug development process is long and expensive, and research and evidence have to show that the drug is effective and safe. From the moment a molecule is investigated until the drug reaches the market, it can take between 10 and 15 years. The development process consists of several phases: the goal discovery phase is to identify an unmet medical need, the therapeutic target, and synthesis of potential candidates. In the pre-clinical phase, in vitro and in vivo pharmacology and toxicology studies are carried out. The clinical phase in which human tests are performed to observe how the drug works in them. And finally, the approval and registration phase, in which the commercialization of the drug is sought. As the development process progresses, the number of candidate molecules to be finally commercialized decreases: of 100 possible proposals that can be provided by in silico studies, around 10 with the best pharmacological properties are synthesized and tested in in vitro studies. . Of these, finally only 1 is the one that manages to reach the clinical and approval and registration phase. Therefore, it is vitally important to know and determine the pharmacological capabilities of a candidate in the early stages of development, in order to ensure that the drug that advances to the later stages is the appropriate one. These pharmacological properties include absorption, distribution, metabolism, elimination, and toxicity; characteristics known under the acronym ADME Tox. The ADME Tox concept describes the effectiveness of a pharmaceutical compound within an organism and is analyzed both in silico, in vitro and in vivo. This work focuses on, on the one hand, making a compilation of the web pages, programs and software available to predict these pharmacological properties in silico; in addition, physicochemical properties such as solubility or pKa, among others. At the same time, the most common in vitro tests used to determine the ADME Tox of a drug are also being sought. These tests on cells and tissues make it possible to obtain the value of the parameters experimentally, thus offering a vision more similar to the reaction of the drug on the human body. On the other hand, with the tools and programs available online, a study was carried out on tyrosine kinase inhibitors used in the therapy of pancreatic cancer. Specifically, three drugs are analyzed: one commercial, Erlotinib, and two experimental drugs synthesized by the Organic Chemistry laboratory of the Pharmaceutical Chemistry Group of the IQS-School of Engineering. After using the different programs and websites, for the three molecules mentioned above, it is concluded that the bibliographic values ​​of Erlotinib, with the predictions obtained, do not differ significantly, and therefore the programs compiled to make predictions in silico provide reliable results.



Borell Bilbao, José Ignacio


IQS SE - Undergraduate Program in Chemistry