lecture 2 Flashcards
how are compounds in development named
the company developing them gives them a name and a number code
how are compounds that show promise as a therapeutic drug named
they are names referring to the disease theyre effective against
saquinavir + ritonavir for antiviral drugs (hiv)
what are marked medicines
medicine with a proprietry (owned by someone)
they have a name that only the owner company can use
nurofen, calpol etc
what is a proprietry name
a name given by the company that owns the medicine
the name is specific to the drug formulation
what is generic medicine
a drug that isnt covered by a patent application
many companies can sell, formulate and make profit from it (paracetamol)
similarity between generic medicine vs marketed medicine
same active principle
diff trade name
european law on generic drugs
generic medicines must have a international, non-proprietary name (rINN)
rINN
international
non proprietry name
what is the european, international non proprietary name
usually the name of the drug
paracetamol, ibuprofen
british approved names had to be changed to what
the international
non proprietry
names
what is a drug class
medicine with:
similar chemical structures
same mechanism of action (binds to the same target)
used to treat similar diseases
what is a drug class defined by
a prototype drug
usually the first developed drug in that class
used as a reference to allow comparison
what is the ATC
anatomical
therapeutic
chemical
classification
system
how does ATC classify drugs
classifies the active ingredient based on the organ or system that its therapeutic, pharmacological or chemical properties act upon
aka what does this drug affect!!
what is the purpose of classifying drugs under ATC
allows us to monitor its use for research + improve quality medication use
eg: oh wow this is classified under cardiovascular system so it is probably mostly used for the heart<3
how many levels of ATC are there
5
what is the first level of ATC system
anatomical group it effects
1letter (a,b,c,d)
2nd level of ATC system
therapeutic subgroup
2 digits
what is therapeutics
treatment + healing
what is pharmacological
uses + effects
third level of ATC system
indicated the therapeutic/pharmacological subgroup
1 letter
forth level of ATC system
chemical/therapeutic/pharmacological subgroup
1 letter
5th level of ATC system
chemical substance
2 digits
drug definition
raw material from animal/vegetable origin that contains active principles that alterates the normal functioning of the CNS when introduced to the b ody via any administration
drug || definition
a biologically active, chemically pure substance that has a therapeutic action.
- reacts with biological environment + has the ability of curing, mitigating or preventing disease in humans/animals)
mitigating meaning
reducing severity of something
medicine definition
drug in its proper dosage form, used in medication
drug / medicine definition difference
drug: compound
medicine: tablet: its proper dosage
drug target
biological entity (protein/gene) that interacts + has its activity modulated by a particular compound
modulated meaning
controlling somethings influence
druggable meaning
smt is druggable if its activity, behaviour or function, can be modulated by a therapeutic
therapeutic: small molecule/ biologics
biological target example
nucleic acids
proteins
7 stages from finding a drug to getting it on the market
- early stage research + discovery
- preclinical studies in animals
- phase 1
- phase 2
- phase 3
- fda review + approval
- post approval
what is phase 1 clinical development
focuses on safety
20-80 healthy ppts
1-2 years
what is phase 2 of the clinical development
efficacy + safety
100-300 patients
1-2 years
what is phase 3 clinical development
efficacy + safety
1,000-3,000 patients
2-3 years
how long does approval from the fda last
1 - 2 years
how many compounds are are lost during the process
from 5,000 - 10,000 (drug discovery + preclinical)
to 1 fda approved drug (fda review)
how much does drug discovery cost + take
from the original idea to launching the finished product
1.5 billion dollars
12 - 15 years
what must u do before identifying a target
find an unmet medical need
we must identify a disease in order to identify targets
who is the concept of unmet medical need important to
stakeholders and regulators
what is a stakeholder
rich companies that have interests in ‘x’
what is a regulator
payers
academics
pharma industries
health technology assessment agencies (HTA)
whats so important about unmet medical needs
theyre personal to everyone
everyones unmet need is different
should focus on all unmet needs as theyre all uncomforatble (not just unmet needs for critical or debilitating conditions)
whats a debilitating condition
a condition that makes someone weak or infirm
how and where do UMN occur
- when current therapies that are available do not address a condition
- when there are no approved molecules
- when there are a few molecules in the late part of clinical studies (not out yet)
- existing molecules are compromised by taking the effective dose of ‘x’.
development of new medicine is driven by what ambition
treating unmet medical needs
the UMN drives ppl to want to meet these needs.
list of therapeutic areas
-cancer
-cardiovascular diseases
-diabetes
-hiv , aids
- immune system diseases
- neurodegenerative diseases
- viral diseases
what is a drug target
a biomolecule that is directly associated with the disease + is responsible for the cellular or molecular function
drug target examples
enzymes // proteins
receptors
metabolic pathways / apoptosis
lipid membrane
ion channles
dna/rna
what is the benefit of discovering a drug target
allows researchers to optimize the drug for a particular disease or condition
optimise meaning
make it the best
identify its most effective use
drug target characteristics
- confirmed role in pathophysiology of a disease/ is disease modifying
- expression is not evenly distributed throughout the body
- its 3d structure is availabe to assess druggability
- easily assayable/tested allowing screening
- has a promising toxicity profile, adverse affects can be predicted using phenotypic data
- favourable intellectual property status (IP) (relavent for big pharma as it shows how its marketed and sold)
what is the modern drug discovery process
target identification
target charactisation
target validation
initial hypothesis in drug discovery
that a particular molecule is the key or causes a pathogenic or symptomatic mechanism in a disease.
eg: hypothesising that this molecule causes the inflammation etccc.
target identification in drug discovery
identifying the function of a possible therapeutic target (gene/protein) and its role in the disease
eg: identifying ‘x’ is the drug target bc iit causes the inflammation
in drug discovery what is target identification followed by
target characterisation of the molecular mechanism addressed by the target
- u found the target, now u need to see its mechanism for how it causes the inflammation
target validation in drug discovery
shows that modulation of the target is likely to have a therapeutic effect
modulation meaning
controlling its influence
what is the goal in target identification
to find a biological target (protein//nucleic acid) whos activity can be regulated with a therapeutic
target identification techniques
in silico
laboratory
in silico target identification technique
silico screening
machine based methods
experimentation performed by a computer
laboratory target identification technique
biological assays such as expression profiling of rna or proteins
aka measuring which genes from the genome are being expressed in particular cells at any given time
or functional screening: gene knockdown, knockout, overexpression
what is gene knockdown
reducing the genes expression
what is gene knockout
eliminating the gene
what is gene overexpression
turning certain genes on
what is target validation
ensuring that engagement of the target has potential therapeutic benefits
aka if we do smt to the target, will it lead to a positive effect.
2 approaches to target validation
chemical + genetic approach
chemical approach to target validation
involves the use of drugs to show that inhibition of the target results in disease inhibition
genetic approach to target validation
target gene knockdown (reduced expression) - rna
target gene knockout (gene elimination) - gene
target validations can be divided into what 2 groups
in vivo
in vitro lab tests
in vivo division of target validation
use of disease models (animals)
use of animal alternatives: worms, microorganisms, computer models, 3d tissue cultures.
in vitro division of target validation
lab tests
- cell/ tissue based experiments
- parameters are studied (ionic conc, enzyme activity, protein expression profiles)
-study of the targets biological function when bound to different ligands (diff drug candidates)
what is a parameter
a measurable factor that defines a system
stages of early stage research + discovery
target identification
hit generation
lead generation
what is found in the hit generation
%wegotahit!
finding compounds that engage with the bio target + have good properties
what is the lead generation in the early research and discovery stage of drug discovery
%theyretakingthelead
from the possible hits
analysis + improvement of compounds with pharmacological activity, the correct potency, solubility + stability
