LECTURE NOTES –
PRINCIPLES OF
DRUG TARGETS
Claire Snel
MSc Biomedical Sciences year –
September - October 2025
,Inhoudsopgave
Lecture 1 – Introduction/ Principles/ concepts of drug targets ........................................................ 2
Lecture 2 – Drug targets ............................................................................................................... 13
Lecture 3 – From enzymes to receptors 1 ...................................................................................... 29
Lecture 4 – From enzymes to receptors 2 ...................................................................................... 39
Lecture 5 – GPCRs as drug targets ................................................................................................ 56
Lecture 6 – Quantitative pharmacology 1 (chapter 7/8) .................................................................. 73
Lecture 7 - Quantitative pharmacology 2 (chapter 7/8) ................................................................... 91
Pharmacology – Assignment 3 .................................................................................................... 102
Lecture 8 – Miscellaneous targets (chapter 9 & 10) ...................................................................... 111
Lecture 9 – A day in a drugs life 1 (chapter 11) .............................................................................. 116
Lecture 10 – A day in a drugs life 2 (chapter 11) ............................................................................ 126
Lecture 11 – From target to drug ................................................................................................. 137
1
,Lecture 1 – Introduction/ Principles/ concepts of drug
targets
- Fundamental research: design and synthesis of biologically active molecules and the
understanding of their molecular mechanism of action at the level of the target proteins
- Applied research
- Drug discovery needs a mix of people
You should not know structures
but recognize components of
structures
2
,Do we need more drugs?
- ±1500 unique, FDA approved drugs
o à 80% small molecules and 20% biologicals
§ Biologicals: proteins, mAb (monoclonal antibodies), vaccines (mRNA or
DNA vaccins)
Why do we need more drugs?
- Why we need more drugs:
o Resistance (bacteria, cancer)
o Better safety profiles
o New diseases
o Curation instead of systematic treatment
o Economy (stock market needs)
Not all diseases are well-treated!
- Example of diseases that were not well-treated:
o COVID-19 à 1.8 million deaths
o Ebola à 50% of the people experiencing ebola dies
Do we need more drugs?
- Still great unmet medical need
- Most drugs give relief of symptoms
- Some disease are still not targeted well
From relief to cure..
- Treatment of gastric ulcers:
o Before 1970’s à operation
o 1970’s à prevent H+ secretion via H2-antagonist cimetidine (daily treatment)
o Now à ulcers are caused by bacteria (Helicobacter Pylori), therefore using
antibiotics to kill the bacteria and eliminate the problem
New drugs might help NL?
- Topsectorplan Life Sciences & Health à roadmap pharmacotherapy
- New pharmacotherapy
o Healthy ageing
o Control budget
§ Only 9% of the costs are on drugs, but they prevent long-term costs
Beside the medical need for new drugs, there is also an economical aspect involved
Ø Pharma continuously look for new drugs
o Because pharma companies spend a lot of money to discover and develop new
drugs (into research and development)à when a new drug is launched, it is
protected by a patent à the patent lets the company sell it alone for a limited
time and set a high price so they can earn back their research costs
3
, o However, after the patent ends, other companies can copy the drug and sell it
much cheaper
o As a result, the original company’s sales and
profits drop sharply
o To keep making money, pharma companies must
keep inventing new drugs before the old ones lose
their patent protection
Drugs are big business…2022 revenues à
Drug discovery = business
- Pharma important for economy
o High quality jobs
o Dow jones index (is a stock market index that tracks the performance of 30 major
U.S. companies to indicate the overall health of the American stock market and
economy. Higher Dow Jones indices indicate that the stock prices of the 30 major
U.S. companies are rising, showing stronger market confidence and economic
optimism, lower indices indicate that these stock prices are falling, reflecting weaker
market confidence or economic concerns)
§ Some of the world’s largest drug makers are part of this major U.sS. stock
market index
• Pfize
• Johnson & Johnson
• Merck
- Blockbusters: drugs selling for big bucks
o Blockbuster = a medicine that earns billions of dollars in sales each year
o But, patents worthy of billions dollar will be lost in time
§ But the patents on these drugs expire after a limited time (usually around
20 years from filing)
§ Once the patent ends, cheaper generic copies enter the market and sales
of the original drop sharply
- Pharma looks for new blockbusters
o 50 billion dollar each year is invested in R&D (research and development) to
discover new drugs
o A new drug has:
§ 17-20 years patent protection from the start of the development
§ Around 10 years of development after patent, remaining with 10 years of
commercial sales after the drug finally reaches the market (much of the
patent life is used up during drug testing and approval)
à Pharmaceutical companies must keep discovering new blockbuster drugs to replace old
ones whose patents expire, so they can maintain revenue and stay valuable on the stock market
4
, Do we need more drugs? Stock market needs
- “Pipeline problems are increasing the urge to merge”
o The pipeline is a company’s list of new drugs in development
o Many firms struggle to keep enough promising new medicines coming (“pipeline
problems”)
§ If they don’t have enough future products, their future revenue is at risk
- Because developing new drugs is slow, expensive, and uncertain, large pharma
companies often merge with or acquire others to quickly gain new products and stay
attractive to investors
o Example: Merck (a large U.S. pharma company) acquired Schering-Plough, which
earlier had bought Organon BV (a Dutch pharma company)
§ The image of a big fish swallowing smaller fish symbolizes this chain of
takeovers
Pharma reality
- The image show workers removing the Organon sign from a
building
- Timeline at the bottom:
o 2007: Dutch company Organon is bought by Schering-
Plough (price ≈ $14 billion)
o 2009: Schering-Plough itself is bought
by MSD/Merck (price ≈ $41 billion)
- Well-known companies can quickly lose their independence as they are taken over by
larger firms
Pharma reality – change in companies with >1 approved
drug
- Graph:
o Green bars (Entry): number of new
companies each year that achieved at least
one FDA-approved drug.
o Red bars (Exit): number of companies disappearing (through mergers,
acquisitions, or closure).
- Trend: In earlier decades there were steady new entrants (green).
- From the 1990s onward, exits (red) increase sharpl > many more companies disappear
than new ones enter
o This means that the industry is consolidating
o Fewer independent drug companies survive because:
§ Developing drugs is expensive and risky
§ Big players buy smaller ones to fill their pipelines
5
PRINCIPLES OF
DRUG TARGETS
Claire Snel
MSc Biomedical Sciences year –
September - October 2025
,Inhoudsopgave
Lecture 1 – Introduction/ Principles/ concepts of drug targets ........................................................ 2
Lecture 2 – Drug targets ............................................................................................................... 13
Lecture 3 – From enzymes to receptors 1 ...................................................................................... 29
Lecture 4 – From enzymes to receptors 2 ...................................................................................... 39
Lecture 5 – GPCRs as drug targets ................................................................................................ 56
Lecture 6 – Quantitative pharmacology 1 (chapter 7/8) .................................................................. 73
Lecture 7 - Quantitative pharmacology 2 (chapter 7/8) ................................................................... 91
Pharmacology – Assignment 3 .................................................................................................... 102
Lecture 8 – Miscellaneous targets (chapter 9 & 10) ...................................................................... 111
Lecture 9 – A day in a drugs life 1 (chapter 11) .............................................................................. 116
Lecture 10 – A day in a drugs life 2 (chapter 11) ............................................................................ 126
Lecture 11 – From target to drug ................................................................................................. 137
1
,Lecture 1 – Introduction/ Principles/ concepts of drug
targets
- Fundamental research: design and synthesis of biologically active molecules and the
understanding of their molecular mechanism of action at the level of the target proteins
- Applied research
- Drug discovery needs a mix of people
You should not know structures
but recognize components of
structures
2
,Do we need more drugs?
- ±1500 unique, FDA approved drugs
o à 80% small molecules and 20% biologicals
§ Biologicals: proteins, mAb (monoclonal antibodies), vaccines (mRNA or
DNA vaccins)
Why do we need more drugs?
- Why we need more drugs:
o Resistance (bacteria, cancer)
o Better safety profiles
o New diseases
o Curation instead of systematic treatment
o Economy (stock market needs)
Not all diseases are well-treated!
- Example of diseases that were not well-treated:
o COVID-19 à 1.8 million deaths
o Ebola à 50% of the people experiencing ebola dies
Do we need more drugs?
- Still great unmet medical need
- Most drugs give relief of symptoms
- Some disease are still not targeted well
From relief to cure..
- Treatment of gastric ulcers:
o Before 1970’s à operation
o 1970’s à prevent H+ secretion via H2-antagonist cimetidine (daily treatment)
o Now à ulcers are caused by bacteria (Helicobacter Pylori), therefore using
antibiotics to kill the bacteria and eliminate the problem
New drugs might help NL?
- Topsectorplan Life Sciences & Health à roadmap pharmacotherapy
- New pharmacotherapy
o Healthy ageing
o Control budget
§ Only 9% of the costs are on drugs, but they prevent long-term costs
Beside the medical need for new drugs, there is also an economical aspect involved
Ø Pharma continuously look for new drugs
o Because pharma companies spend a lot of money to discover and develop new
drugs (into research and development)à when a new drug is launched, it is
protected by a patent à the patent lets the company sell it alone for a limited
time and set a high price so they can earn back their research costs
3
, o However, after the patent ends, other companies can copy the drug and sell it
much cheaper
o As a result, the original company’s sales and
profits drop sharply
o To keep making money, pharma companies must
keep inventing new drugs before the old ones lose
their patent protection
Drugs are big business…2022 revenues à
Drug discovery = business
- Pharma important for economy
o High quality jobs
o Dow jones index (is a stock market index that tracks the performance of 30 major
U.S. companies to indicate the overall health of the American stock market and
economy. Higher Dow Jones indices indicate that the stock prices of the 30 major
U.S. companies are rising, showing stronger market confidence and economic
optimism, lower indices indicate that these stock prices are falling, reflecting weaker
market confidence or economic concerns)
§ Some of the world’s largest drug makers are part of this major U.sS. stock
market index
• Pfize
• Johnson & Johnson
• Merck
- Blockbusters: drugs selling for big bucks
o Blockbuster = a medicine that earns billions of dollars in sales each year
o But, patents worthy of billions dollar will be lost in time
§ But the patents on these drugs expire after a limited time (usually around
20 years from filing)
§ Once the patent ends, cheaper generic copies enter the market and sales
of the original drop sharply
- Pharma looks for new blockbusters
o 50 billion dollar each year is invested in R&D (research and development) to
discover new drugs
o A new drug has:
§ 17-20 years patent protection from the start of the development
§ Around 10 years of development after patent, remaining with 10 years of
commercial sales after the drug finally reaches the market (much of the
patent life is used up during drug testing and approval)
à Pharmaceutical companies must keep discovering new blockbuster drugs to replace old
ones whose patents expire, so they can maintain revenue and stay valuable on the stock market
4
, Do we need more drugs? Stock market needs
- “Pipeline problems are increasing the urge to merge”
o The pipeline is a company’s list of new drugs in development
o Many firms struggle to keep enough promising new medicines coming (“pipeline
problems”)
§ If they don’t have enough future products, their future revenue is at risk
- Because developing new drugs is slow, expensive, and uncertain, large pharma
companies often merge with or acquire others to quickly gain new products and stay
attractive to investors
o Example: Merck (a large U.S. pharma company) acquired Schering-Plough, which
earlier had bought Organon BV (a Dutch pharma company)
§ The image of a big fish swallowing smaller fish symbolizes this chain of
takeovers
Pharma reality
- The image show workers removing the Organon sign from a
building
- Timeline at the bottom:
o 2007: Dutch company Organon is bought by Schering-
Plough (price ≈ $14 billion)
o 2009: Schering-Plough itself is bought
by MSD/Merck (price ≈ $41 billion)
- Well-known companies can quickly lose their independence as they are taken over by
larger firms
Pharma reality – change in companies with >1 approved
drug
- Graph:
o Green bars (Entry): number of new
companies each year that achieved at least
one FDA-approved drug.
o Red bars (Exit): number of companies disappearing (through mergers,
acquisitions, or closure).
- Trend: In earlier decades there were steady new entrants (green).
- From the 1990s onward, exits (red) increase sharpl > many more companies disappear
than new ones enter
o This means that the industry is consolidating
o Fewer independent drug companies survive because:
§ Developing drugs is expensive and risky
§ Big players buy smaller ones to fill their pipelines
5
