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Author: Good Lentils
As the highest honor in the scientific community, the Nobel Prize has gone through more than a century
In the past 100 years, scientists have made a series of breakthrough discoveries and research progress, and made pioneering contributions to the development of science and the progress of human society
Among the research projects and achievements of these winners, which ones have opened up new ideas and directions for mankind to overcome diseases? What are the potential applications for drug development?
Let’s count them down and fall into the history of human natural science, and they belong to the most shining star of "medicine research and development"
31 Nobel Prize drugs or treatments
31 Nobel Prize drugs or treatmentsSince the first Nobel Prize in Physiology or Medicine was awarded in 1901, countless new drugs have been discovered in 120 years, and they have extremely important significance in the course of human history
According to incomplete statistics, there are 31 drugs or therapies related to the Nobel Prize.
Table 1 Nobel Prize-winning drugs/therapies
In addition to the familiar artemisinin and PD-1, there are subversive and revolutionary therapies that have been popular for a long time.
3 popular treatments
3 popular treatmentsIn recent years, several popular areas that have opened new doors and paved new tracks for new drug research and development or disease treatment:
(1) Negative immunomodulatory cancer therapy, a new milestone in the history of human anti-cancer
Cancer includes many kinds of diseases.
There are many treatments for cancer, such as surgery and radiotherapy, some of which have also been awarded Nobel Prizes.
However, most of these therapies are suitable for early stages, and there is still a lack of effective methods for advanced cancer.
In the human immune system, there are T cells that play the role of "policeman".
However, the "police" is not as many as possible.
Therefore, under normal circumstances, the human body will use a mechanism similar to the "brake" system to make T cells close in time.
However, the researchers found that cunning cancer cells have also evolved a super strong "braking" ability to escape the attack of immune cells
Therefore, scientists have developed immunotherapies that inhibit CTLA-4 and PD-1, and eliminate them by removing the "braking" system of cancer cells
The emergence of immunotherapies represented by anti-CTLA-4 antibodies and anti-PD-1 antibodies is a milestone in the history of humans to overcome cancer.
In 2018, the Nobel Prize in Physiology or Medicine was awarded to the discoverers of CTLA-4 and PD-1 in recognition of their pioneering contributions in the field of cancer immunotherapy
Figure 1 The mechanism of action and inhibition of CTLA-4 and PD-1
Image source: Nobel Prize official website
(2) Re-programming mature cells, a weapon to cross the barrier of regenerative medicine
Stem cells are a type of cell with unlimited or immortal self-renewal ability
.
Embryonic stem cells can develop into various cell types in mature organisms such as nerve cells and muscle cells.
This process has long been considered to be one-way and irreversible
.
However, reprogramming technology can force mature cells to accept a new fate and "rejuvenate" to become iPS cells that can generate all cell types in the body
.
Cell reprogramming skillfully bypasses the ethical dilemma of embryonic stem cells "killing to save people", and is considered to have broad prospects for medical applications
.
Even better, these iPS cells can be the patient's own, and there is no need to consider the potentially lethal effects of cells or organs from other people.
This is a huge temptation for any doctor
.
This revolutionary discovery opened up a new world for the treatment of diseases
.
In 2012, the Nobel Prize in Physiology or Medicine was awarded to two scientists in the United Kingdom and Japan, which inspired unprecedented enthusiasm for stem cell technology
.
Globally, in addition to stem cell transplantation, more than ten first-generation stem cell therapy products have been approved for clinical use in the treatment of acute myocardial infarction, graft-versus-host disease in children and other diseases
.
With the rise of a new generation of stem cell therapy, it is expected to bring new options for the treatment of inflammation, autoimmune diseases, heart failure, stroke, Parkinson's disease, diabetes, and genetic diseases
.
Figure 2 Schematic diagram of the principle of iPS cell reprogramming
Image source: Beijing Nuowei Bio
(3) Ubiquitin-proteasome system, new ideas for targeted therapy
Since the human genome was interpreted, researchers have been trying to target thousands of disease-causing proteins
.
It is estimated that only 10% of proteins can be regulated by small molecules, and 10% of proteins that can be regulated by biological macromolecules are on the cell surface, which means that traditional small molecule and antibody drugs can only target about 20% of proteins, and up to 80% of the protein cannot be controlled with existing drugs
.
The reason behind many serious diseases is the dysfunction of protein
.
80% of the proteins that have been labeled as "non-medicinal" have become a huge and attractive vacuum zone for targeted therapy
.
The protein degradation therapy based on the ubiquitin-proteasome system is expected to overcome this problem
.
In the ubiquitin-proteasome system, the cell will add some ubiquitin molecules to the protein that needs to be degraded, which is like marking the "garbage" as "recyclable"
.
Then, these ubiquitin-labeled proteins are sent to the proteasome in the cell
.
The latter is like a garbage disposal center, which can break down proteins into short peptides and amino acids for cells to synthesize other proteins
.
This amazing discovery won the 2004 Nobel Prize in Chemistry
.
At present, scientists are developing protein degradation therapies, with a view to treating prostate cancer, breast cancer, autoimmune diseases and other diseases
.
Figure 3 PROTACs technology like dumbbells
Image source: Nature
In addition to the above, there are many innovative technologies and therapies based on Nobel Prize discoveries, such as hepatitis C treatment drugs, RNAi, CDK 4/6 inhibitors, insulin, monoclonal antibodies, in vitro fertilization technology and so on
.
The next Nobel Prize direction?
The next Nobel Prize direction?In the future, what kind of inspiration can we get from the Nobel Prize?
(1) The pace of revealing the answer has never stopped
.
It is not difficult to see that the Nobel Prize is basically to broaden the boundaries of mankind and explore unknown original major innovations
.
It is not necessarily a new thing, but it must be a profound analysis of scientific mysteries
.
For example, the 2019 Nobel Prize in Physiology or Medicine is awarded to scientists who have made important contributions in the field of oxygen sensing pathway research
.
Oxygen is essential to the survival of humans and most animals, and is widely known
.
Their research results reveal the mechanism of one of the most basic adaptive processes in life, which is encouraging, and clarifying the biological oxygen sensing pathway is of great significance to the research and development of innovative drugs
.
When we are studying the mechanism of action, we might as well go one step further, there may be unexpected gains
.
(2) Learn by analogy and get inspiration from Nobel Prize research
.
Since the first Nobel Prize in Physiology or Medicine was awarded in 1901, according to incomplete statistics, only more than 30 products have been developed into a series of blockbuster products, and about three-quarters of the Nobel Prize achievements are still on the way or Waiting to be excavated, these results are like treasure mines, waiting for application development
.
Finally, I pay tribute to all the scientists who have made contributions in conquering human diseases and improving human health.
I hope they can make more breakthrough discoveries in the future and bring new and more powerful weapons to mankind to overcome diseases!