Module 1 Flashcards
A process which is intended to identify a small synthetic molecule or a large bio-molecule for comprehensive evaluation as a potential drug candidate
Drug Discovery
researchers discover new
drugs through:
• N-new insights into a disease process
• M-many tests of molecular compounds
• E-existing treatments that have unanticipated effects.
• N-new technologies
The _____ are
further optimized to improve
their efficacy and
pharmacokinetics before
they advance towards drug
development
lead compounds
The process of bringing a new pharmaceutical drug to the
market once a lead compound has been identified
through the process of drug discovery.
DRUG DEVELOPMENT
It includes preclinical research on microorganisms and animals, filing for regulatory status, such as via the United States Food and Drug Administration for an investigational new drug to initiate clinical trials on humans, and may include the step of obtaining regulatory approval with a new drug application to market the drug.
DRUG DEVELOPMENT
Once researchers identify a promising compound for development, they conduct experiments to gather information
on:
• How it is absorbed, distributed, metabolized, and excreted.
• Its potential benefits and mechanisms of action.
• The best dosage.
•The best way to give the drug (such as by mouth or injection).
• Side effects or adverse events that can often be referred to as toxicity.
• How it affects different groups of people (such as by gender, race, or ethnicity) differently.
• How it interacts with other drugs and treatments.
• Its effectiveness as compared with similar drugs.
Before testing a drug in people,
researchers must find out whether it has the potential to cause serious
harm, also called toxicity.
PRECLINICAL
DEVELOPMENT
The two types of preclinical research are:
In Vivo
In Vitro
In preclinical development, toxicological and safety pharmacology studies of the candidate are conducted in order to
establish the ________ in animals and determine the adverse effect
potential of the drug-in-development.
maximum safe concentrations
FDA requires researchers to use __________, defined in medical product development regulations, for preclinical laboratory studies.
minimum basic requirements for:
• study conduct
• personnel
• facilities
• equipment
• written protocols
• operating procedures
• study reports
Good laboratory practices
(GLP)
The GLP regulations are found in ________: Good Laboratory Practice for Nonclinical Laboratory
Studies.
21 Code of Federal Regulations (CFR) Part 58.1:
Studies are conducted
to finalize ___________ required for
manufacturing the candidate drug as well as __________
Cost-effective processes…deciding on its best formulation
The trigger to initiate a drug discovery program is a medical condition whose treatment is not satisfactorily addressed by currently available treatment modalities.
IDENTIFICATION OF UNMET MEDICAL NEED
The trigger to initiate a drug discovery program is a medical condition whose treatment is not satisfactorily addressed by currently available treatment modalities.
IDENTIFICATION OF UNMET
MEDICAL NEED
Biologically active compounds, whether they be a small synthetic molecule or a large molecular weight antibody, elicit their activity and thereby a measurable clinical effect by interacting with a naturally existing molecular structure
TARGET IDENTIFICATION
Examples of target molecules:
• Enzymes
• Receptors
• Metabolites
• Substrates
• Ion channels
• Transport proteins
• DNA, RNA, and ribosomes
Have been scientifically proven to have well-defined physiological and pathophysiological roles fall.
Established targets
Newly discovered ones whose role is turning out to be clearer with advancing research
Novel Targets
A potential drug target needs to undergo the process of validation where in its function in a disease state is ascertained
TARGET VALIDATION
Next step is identification of ‘hits’, which in a broad
sense may be defined as compounds that elicit the
desired activity in a screening assay
5 examples:
• High throughout screening (HTS)
method
• Fragment-based screening
• Focused screening strategy
• Phenotypic screening
HIT IDENTIFICATION & DEVELOPMENT OF ASSAYS
The identified hits are subjected to confirmatory evaluation using the same assay conditions which were employed during hit identification
It is imperative to ascertain that the activity is linked to the anticipated mechanism and is not due to artifacts.
CONFIRMATION OF HITS
Procedure of detecting false
positives is to employ a counter-
screening assay in which hits are
evaluated for their activity
against an alternative member of
the target family under identical
assay conditions and if the hit
demonstrates similar activity
then it is most likely a false
positive.
NA
Also referred to as hit to lead phase, involves optimization of the identified hits from a diverse series to generate lead compounds
LEAD GENERATION
In this stage, compounds synthesis is initiated by medicinal chemists by using various approaches like conventional organic chemistry and combinatorial chemistry.
Screening flow for lead identification comprises of in vitro evaluation in primary/cell-free assays as well as specificity of the compounds for the
target.
Further, the activity of compounds is
also evaluated in known animal orthologs of the target as
the compounds have to be evaluated for
their efficacy in animal models.
LEAD GENERATION
