Glossary Flashcards
A therapeutic target is in general a macromolecule (typically a protein), which may cause or be associated with a particular disease, that can be modulated by a therapeutic agent in a measurable way.
TARGETS OR DRUG TARGETS
Are macromolecule, made up of deoxynucleic acid (DNA) based. In humans they vary in size from a few hundred DNA bases to more than 2 million bases and about 20,000 to 25,000 have been identified.
GENES
How many genes have been identified?
20,000 to 25,000
process of separation and characterization of all the proteins of a biological system. Target identification can be performed by comparing the protein expression levels in normal and diseased
tissues.
PROTEOMICS
Diverse molecules from biological origins that include, nucleic-acids, various (recombinant) proteins, antibodies. some types of peptides.
BIOLOGICS
typically have a high molecular weight
BIOLOGICA
large biomolecules (up to thousands of atoms) that comprise one or more chains of amino acids.
PROTEINS
are products of genes; they generally fold into a specific three-dimensional (3D) structure that determines their activities.
PROTEINS
short chains of amino acids.
PEPTIDES
Some peptides belong to the category of_____ or _____, among others.
GLYCOPEPTIDE
LIPOPEPTIDE
Very short and
modified peptides can behave like small molecules while longer peptides (e.g., insulin which is used to manage
diabetes) fit in the category of biologics. At present, there are very few approved peptides that can be given by oral
route but important work is ongoing in this field to enable oral delivery
PEPTIDES
Any organic compound with around 80–100 atoms. Most are made synthetically (aspirin), while others can be derived from natural product (e.g., morphine, which is used to relieve moderate to severe pain)
SMALL MOLECULES
Small Molecules are organic compound with around______ . Most are made synthetically (aspirin), while others can be
derived from natural product (e.g., morphine, which is used to relieve moderate to severe pain)
80-100 ATOMS
Natural product which is used to relieve moderate to severe pain
MORPHINE
A molecule suitable for clinical testing. The molecule is expected to bind selectively to a target involved in the disease
process, to elicit the desired functional responses in vivo, often in animal models of the human disease, to have
adequate bioavailability and bio-distribution within the body to reach the intended target and to pass formal toxicity
evaluation in various in vitro and animal models
DRUG CANDIDATES
branch of molecular biology that involves extensive analysis of biological data using computers
BIOINFORMATICS
field that attempts to solve chemical problems on the computer, including chemical structure coding, properties modeling and development of databases
CHEMOINFORMATICS
Combines computer sciences and mathematics and uses (large) datasets to enable problem-solving. It includes various learning approaches, natural language processing, knowledge representation and reasoning, among others
ARTIFICIAL INTELLIGENCE (AI)
A drug has to reach the intended target(s), elicit the desired functional response with no or limited toxicity and be eliminated from the body (typically via the liver or
kidneys). These are critical properties of the drug candidates that are commonly investigated at various stages of the
process
ADMET ( ADSORPTION, DISTRIBUTION, METABOLISM, EXCRETION, TOXICITY)
Physiologically-based pharmacokinetic modeling and simulation is a computer modeling approach that incorporates blood flow and tissue composition of organs to define the pharmacokinetics of drug candidates
PB/PK
the time-concentration profile of drugs administered in vivo to living organisms. parameters include clearance, volume of distribution, peak plasma concentration. . . is sometimes described “what the body does to a drug”
PHARMACOKINETICS
efers to the relationship between drug concentration at the site of action and the resulting effect, including the time course and intensity of therapeutic and adverse effects.
PHARMACODYNAMICS
parameters include minimum effective concentration, maximum safe concentration, onset of action, therapeutic range and therapeutic index. describes how biological processes in the body respond to or are impacted by a drug
PHARMACODYNAMICS
Relationship of the drug effect (pharmacodynamics) to the drug concentrations in the body compartments (e.g., blood, organs) as a function of time after drug administration
PK/PD
Action of a drug on targets other than the intended biological target. Such events commonly contribute to adverse effects or toxicity, however, in some cases, off-target activity can be valuable for therapeutic purposes
OFF TARGET ACTIVITY
A drug is usually designed to interact with its intended target. In some situations, the drug induces exaggerated and adverse pharmacological effects at the target of interest. This is commonly referred in the literature to as on target toxicity
ON TARGET TOXICITY
Unintended pharmacological effects that occur when a medication is administered correctly. There are different types of reactions (mild, moderate or severe) that can be dose-dependent or not
ADVERSE EVENTS
Secondary unwanted effects that occurs due to the drug therapy. Side effects are usually known and patients are
informed about such effects
SIDE EFFECTS
- Preclinical studies are a stage of research that precedes clinical trials (testing in humans). The therapeutic agents are
tested in animal models of human diseases or in systems that simulate human diseases. - The main goals are to
determine a starting, safe dose for first-in-human study and assess potential toxicity. Research into early formulations (e.g., tablet, capsule, intramuscular injection, intravenous, sublingual. . .) is also performed
PRECLINICAL DEVELOPMENT
Research studies performed in humans aiming at evaluating the efficacy (does the drug cure or slow the progression
of a disease?) and safety (does the drug cause undesired effects, or toxicity?) of drug candidates.
CLINICAL TRIALS
Aka“first-in-humans” trial. Test on 20–80 healthy volunteers to assess the safety and pharmacokinetics, absorption,
metabolism, and elimination, actions on the body, as well as possible side effects, formulation, and dose. In some
cases, a placebo can be used. For some drugs, a phase 0 can be sometime performed before phase I to evaluate some properties of the drug on few patients or on healthy individual
PHASE I
Assesses drug safety and efficacy on about 100–500 patients (suffering from a specific disease), some of which may
receive a placebo or an approved drug for that disease, called“standard of care”. Analysis of optimal dose is performed while adverse events and risks are recorded
PHASE II
enrolls numerous patients (e.g., 1,000–5,000), enabling medication labeling and instructions for proper drug use. Efficacy, dose, and toxicity are observed and adjustments to the final medication label are being made based on such information
PHASE III
Following drug approval and manufacturing, regulatory agencies require companies to monitor the safety of the approved drug. Drug makers, health professionals, hospitals and patients report adverse events occurring when taking the approved drug
Phase IV or pharmacovigilance or“real world evidence”
The dosage (a range of concentrations) of a drug that provides efficacious therapy and is safe (without serious side effects)
THERAPEUTIC WINDOW
The process in which the therapeutic agent is combined with different substances to produce a final medicinal
product (e.g., a tablet, infusion solution, etc.). Formulation optimization is ongoing throughout pre-clinical and clinical stages. It ensures drugs are absorbed into the body and delivered to the proper organ at the right time and the right amount
DRUG FORMULATION
exclusive right granted by the governments for an invention. Patents give an inventor (academic group
or a private company) the exclusive right to prevent others from making, using, selling, or importing a product or
process based on the patented invention without the inventor’s prior permission, such as through a patent license.
Patent protection is limited to the country or region where it was issued and limited in time, typically 20 years from the date of patent application filing. Pharmaceutical patents can be extended for new indications or novel formulations.
PATENT
