ADME-Tox properties describe the chemical and physical properties that affect the Absorption, Distribution, Metabolism, Elimination and Toxicity of a compound.
A biomarker, or biological marker, is an indicator of a biological state. It is a characteristic that can be objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic response on therapeutic intervention.
An organized and systematic collection of data that can be accessed immediately and manipulated by a data-processing system for a specific purpose.
Dihydrofolate reductase (DHFR):
A folate pathway protein responsible for the reduction of biological folates that are important for key biological processes such as DNA and protein biosynthesis.
A blanket term used to define the process of bringing a new drug to the market once a lead compound has been identified through the process of drug discovery.
In silico studies:
Computational studies and computer simulations.
In vitro testing:
Studies performed on isolated cellular components like purified proteins or cultured cells outside their usual biological environment.
In vivo testing:
Studies performed in living beings (microorganisms, animals) to assess compound action in a normal biological context.
A compound with likely therapeutically useful pharmacological action, that typically requires further structural optimization. Required properties to consider a compound a lead can be defined by the Target Drug Lead Profile.
Medium/High-Throughput-Screening assays are assay methods with limited requirements of time and material, that can screen hundreds to thousands of compounds for their pharmacological/biological activity in a single assay run.
Mechanism of Action (MoA):
The mechanism of action describes all the biochemical interactions responsible for the pharmacological effect of a drug compound or candidate.
Neglected Tropical Diseases (NTDs):
Diseases that are endemic in many tropical and sub-tropical countries, such as Chagas disease, sleeping sickness or leishmaniasis, caused by the parasites Trypanosoma cruzi, Trypanosoma brucei and Leishmania spp., respectively. Despite a strong and urgent medical need, these diseases are neglected by the pharmaceutical industries which have limited interest in searching for new safe and more effective drugs.
Pharmacodynamic (PD) parameters:
Pharmacodynamic parameters describe the chemical and physical properties of a molecule that affect its effect, such as the biological action or efficacy. Pharmacodynamics more precisely cover every effect a compound has on the organism it is administered to.
Pharmacokinetic (PK) parameters:
Pharmacokinetic parameters describe the chemical and physical properties of a molecule that affect its ADME-Tox profile: Pharmacokinetics characterize how the organism affects the compound.
Proteomics aim to study proteins on a large scale by investigating entire sets of proteins present in a whole organism, as well as changes in this proteome associated e.g. with drug treatment.
Pteridine reductase 1 (PTR1):
A folate pathway protein unique to Trypanosomatid parasites. Its physiological activity is the reduction of biopterin species, but it serves as a metabolic bypass when DHFR is inhibited, can reduce folates and thereby act as a player in antifolate resistance.
TPP and TDLP criteria:
TPs (Target Profiles) are ensembles of properties that compounds
must feature before they can pass on to the next stage of drug development. These
criteria define which molecules will move forward during the different stages
of the drug development process to ensure that only the most promising compounds
progress towards clinical studies.
The Target Drug Lead Profile or TDLP for instance defines properties required for a compound to be considered a drug lead.
A Target Product Profile or TPP goes beyond this and defines the desired profile of a final target product dedicated to combating a specific disease, considering aspects like intended use, safety and efficacy levels to aim at.