glossary

Question 1

A therapeutic target is in general a ______, which may cause or be associated with a particular disease, that can be modulated by a therapeutic agent in a measurable way

Answer 1

macromolecule (typically a protein)

Question 2

These are macromolecules, made up of deoxynucleic acid (DNA) bases.

Answer 2

Genes

Question 3

In humans, genes vary in size from a few hundred DNA bases to more than 2 million bases and about 20,000 to 25,000 genes have been identified.

Question 4

It is the process of separation and characterization of all the proteins of a biological system. Target identification with proteomics can be performed by comparing the protein expression levels in normal and diseased tissues

Answer 4

Proteomics

Question 5

Diverse molecules from biological origins that include, nucleic-acids, various (recombinant) proteins, antibodies . . . some types of peptides.

• It typically have a high molecular weight

Answer 5

Biologics

Question 6

These are large biomolecules (up to thousands of atoms) that comprise one or more chains of amino acids.

It performs a vast array of functions within organisms, often through interactions with other macromolecules.

Answer 6

Proteins

Question 7

Proteins are products of __; they generally fold into a specific three-dimensional (3D) structure that determines their activities. There are different types of proteins with different functions and locations in the body

Answer 7

genes

Question 8

These are short chains of amino acids. They can be modified to include non-natural amino acids (up to hundreds of atoms).

Answer 8

Peptides

Question 9

Some peptides belong to the category of ______, among others.

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

Answer 9

glycopeptide or lipopeptide

Question 10

Small molecules are any organic compound with ____. 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)

Answer 10

around 80–100 atoms

Question 11

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

Answer 11

Drug candidates

Question 12

It is a branch of molecular biology that involves extensive analysis of biological data using computers

Answer 12

Bioinformatics

Question 13

It is a field that attempts to solve chemical problems on the computer, including chemical structure coding, properties modeling and development of databases

Answer 13

Chemoinformatics

Question 14

as used today (the so-called weak AI), it 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

Answer 14

Artificial Intelligence (AI)

Question 15

ADMET

Answer 15

Absorption
Distribution
Metabolism
Excretion
Toxicity

Question 16

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.

Answer 16

ADMET

Question 17

It is a computer modeling approach that incorporates blood flow and tissue composition of organs to define the pharmacokinetics (PK) of drug candidates.

Answer 17

Physiologically-based pharmacokinetic modeling and simulation (PB/PK)

Question 18

It is the time-concentration profile of drugs administered in vivo to living organisms. Its parameters include clearance, volume of distribution, peak plasma concentration . . It is sometimes described as “what the body does to a drug”

Answer 18

Pharmacokinetics (PK)

Question 19

It refers 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. Its parameters include minimum effective concentration, maximum safe concentration, onset of action, therapeutic range and therapeutic index.

It describes how biological processes in the body respond to or are impacted by a drug.

Answer 19

Pharmacodynamics (PD)

Question 20

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

Answer 20

PK/PD

Question 21

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

Answer 21

Off-target Activity

Question 22

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:

Answer 22

On-Target toxicity

Question 23

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

Answer 23

Adverse events

Question 24

Secondary unwanted effects that occurs due to the drug therapy. These are usually known and patients are informed about such effects.

Answer 24

Side effects

Question 25

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.

Answer 25

Preclinical studies

Question 26

The main goals of preclinical studies 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.

Question 27

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.

Answer 27

Clinical Trials

Question 28

Human clinical research is tightly regulated by authorities around the world. Examples are:

Answer 28

US Food and Drug Administration (US FDA)
and European Medicines Agency (EMA)

Question 29

Pharmaceutical companies and other organizations developing drugs have to conduct extensive preclinical evaluations, propose the design of clinical trials and formally submit these data and a clinical plan to regulatory authorities. If regulatory authorities approve the proposed strategy, Phase I (first-in- humans) clinical trial can start. Each study has its own pre-defined rules about which patients can or cannot participate, which is called eligibility

Question 30

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.

Answer 30

Phase I

Question 31

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 individuals

Question 32

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

Answer 32

Phase II

Question 33

It 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

Answer 33

Phase III

Question 34

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

Answer 34

Phase IV / Pharmacovigilance / “Real World Evidence”

Question 35

The dosage (a range of concentrations) of a drug that provides efficacious therapy and is safe (without serious side effects)

Answer 35

Therapeutic window

Question 36

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.).

Answer 36

Drug formulation

Question 37

It 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 in the right amount

Answer 37

Formulation optimization

Question 38

It is an exclusive right granted by the governments for an invention.

It gives 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.

Answer 38

Patents

Question 39

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.

Question 40

in silico - using computer
in vitro - test tube
ex vivo - tissues/organs
in vivo - living organisms