There is huge pressure in R&D under Zheng Li because he understands this industry so well.
The boss is the most knowledgeable person in the entire R&D field. Your R&D progress, R&D difficulty, and R&D ideas cannot fool him at all.
For example, Li Wanqing didn't dare to fool Zheng Li. He always reported on the actual situation according to the actual situation.
Among them, there are two small molecule drugs that Kechuang Biotechnology will carry out clinical trials this year. One of the project leaders is Wang Jinsong. He can be regarded as an early R&D personnel in the company in the field of innovative drug research and development.
He and Cheng Gang are alumni, not from the same class.
At that time, the prospectus for the listing of Kechuang Biotech stated that it would engage in research and development of original drugs. After the successful listing, Wang Jinsong joined Kechuang Biotech.
He has been at Merck before, from Merck's headquarters in New Jersey to Merck in China.
The reason why I came to Kechuang Biotechnology is because there is almost no room to go up in Merck East.
Coming to Kechuang Biotech, there is Cheng Gang. Kechuang Biotech has a very new history, abundant cash flow, and the founder team seems ambitious and has many opportunities.
So Wang Jinsong joined Kechuang Biotech after leaving Merck and was responsible for the research and development of small molecule drugs.
After joining the company, you select a topic and then initiate research and development.
Wang Jinsong originally thought that Zheng Li did not know much about the research and development of small molecule drugs.
First of all, we need to popularize a concept, that is, drug research and development is divided into many fields, mainly divided into chemical small molecule drugs and biological macromolecule drugs.
Endorphins are biological macromolecules, substances that exist in the body itself, but Zheng Li has developed the manufacturing process of endorphins.
Biological macromolecules have larger molecular weights and more complex structures, with molecular masses generally ranging from 1,500 to 150,000.
The molecular weight of small molecule drugs is generally distributed between 200-700.
Historically, from the discovery of penicillin in the 1920s and 1930s until 1982, all previous drugs in the modern medical sense were small molecule drugs.
Penicillin is also a small molecule drug.
The first truly large molecule drug was launched in 1982.
The reason why this phenomenon occurs is that the method of determining the structure of small molecules only requires nuclear magnetic spectrum, hydrogen carbon spectrum and lcms to achieve better results.
However, methods for measuring macromolecular structures are often more complex.
Measurements of biomolecules require higher precision and sensitivity than small molecules.
Of course, this does not mean that the research and development of biological macromolecules is definitely higher than that of small chemical compounds.
The most important means of modern small molecule drug development is screening.
To sift, first you need to have a sieve, and secondly, you need to have a library with enough things for you to sift through. Then you need to know what the things in the library are and what they look like. Finally, you need to find out what you sift out. To be able to produce in large quantities.
In recent years, there have also been new methods. The research and development of small molecule drugs by Kechuang Biotech adopts new technical methods.
But historically, especially in the 1990s when the pharmaceutical industry was booming, screening methods were the mainstream among the mainstream.
Screening refers to experiments based on various disease indicators, where small chemical molecules are put into corresponding experiments to see which ones are effective.
The so-called library refers to a molecular library, due to the rapid development of organic synthesis methods in the 1970s and 1980s.
A large number of complex, stable, heterocyclic molecules that were originally difficult to synthesize began to appear in batches.
The advancement of detection methods such as nuclear magnetic resonance and mass spectrometry has led to the successful isolation of many natural products. The successful isolation of these natural products has promoted the synthesis of other types of molecules.
So by the 1990s, pharmaceutical companies already had millions of different types of small molecules in their libraries.
The development of biotechnology during this period led to the discovery of some important disease indicators and targets.
These discoveries enabled biopharmaceutical giants to use millions of small molecules at their disposal to screen for these diseases and targets, leading to an explosion of new drugs in the 1990s.
The distance between China's biopharmaceutical companies and the world's pharmaceutical giants was mainly widened during this period.
While others are doing targeted analysis, domestic progress in this area is slow.
There is a data that can indirectly prove this, that is, in 1985, China began to implement a new drug registration method.
From 1985 to 2008, China approved only 5 new Class I drugs in 23 years.
The first time Wang Jinsong heard the name Zheng Li was in "nature", when he was still at Merck's headquarters.
At that time, many people internally were discussing that the laboratory preparation method of endorphins was developed by a Chinese.
Wang Jinsong was amazed by the ingenious experimental design. Later, when he found out that he was still a freshman and even in the School of Mathematics, Wang Jinsong became suspicious.
The more people in the industry understand, the more difficult it is to develop biomacromolecule drugs, even if the biomacromolecule is a peptide substance that exists in the organism itself.
But if a substance discovered in the 1950s is so easy to manufacture, how could it be left to you to discover?
Including Wang Jinsong’s internal historical documents at Merck, we have seen that in the 1980s, Merck’s internal R&D team spent two years without solving this problem.
Later, I learned about Zheng Li. It was when Zheng Li developed an industrial-scale manufacturing method for endorphins, and Kechuang Biotech started patent licensing negotiations with major international pharmaceutical companies around endorphins.
Only then did Wang Jinsong believe that there was such a genius in the world.
Because it is possible to buy a Nature paper, but it is impossible to let others transfer industrialized manufacturing methods.
Especially after the clinical data of endorphins came out, it was almost able to crowd out morphine drugs, making them unable to fight back.
No one would be so generous as to give away such a huge benefit.
Later, Wang Jinsong joined Kechuang Biotechnology. Not long after he joined, Zheng Li went to the Lion City.
But every time during a remote video conference, Zheng Li's views and ideas on small molecule drugs would make him feel enlightened.
"Dr. Zheng, we plan to use a dual-fluorescence cell cycle reporter system to mark cells in the s-g2-m phase of mitosis and then display cytokinesis.
In addition, a high-throughput screening system was constructed to screen out 13 small molecules that can effectively induce cardiomyocytes to enter the cell cycle from a chemical small molecule library.
Except for mct1 inhibitors, other single small molecules cannot induce cardiomyocyte cytokinesis. "
“You can try to combine small molecules in pairs or more to verify the efficacy.
Also remember to build a mathematical model to predict the best combination of small molecules to promote proliferation. I will send you a mathematical model I built before later, so you can refer to my design ideas. "
Wang Jinsong's group mainly plans to develop small molecule drugs for cardiovascular diseases.
Later, Wang Jinsong and others followed Zheng Li's idea and discovered through in vitro and in vivo experimental verification that they found a small molecule combination 5sm composed of phenylephrine hydrochloride, baricitinib, dehydrocameline, pten inhibitor and mct1 inhibitor. , can successfully induce adult mouse and human cardiomyocytes to re-enter the cell cycle and undergo cytokinesis.
In other words, it can promote heart regeneration and treat myocardial infarction.
(The above research ideas come from a paper published by the School of Chemistry and Molecular Sciences of Yenching University in the cell sub-journal in April this year:
"a small-molecule cocktail promotes mammalian cardiomyocyte proliferation and heart regeneration")
They then established a mouse myocardial infarction model and found that 5sm could significantly improve the heart function of adult mice after myocardial infarction and reduce the area of cardiac fibrosis.
Wang Jinsong and his team found that 5sm induced quiescent cardiomyocytes to enter a dedifferentiation state and then enter a proliferation state.
5sm promotes the conversion of cardiomyocyte metabolism from oxidative phosphorylation to glycolysis by activating lactate signaling and the mTOR pathway, ultimately inducing cardiomyocyte proliferation and division.
Zheng Li has a better understanding of small molecule drugs than he does.
This made Wang Jinsong doubt his life.
You must know that he started studying biology as an undergraduate, and spent a total of seventeen years from undergraduate to postdoc. Later, he worked for Merck for another eight years. He spent more than twenty years in the research and development of small molecule drugs.
But the facts are in front of him. Zheng Li can think of what he can think of, and Zheng Li can still think of what he can't think of.
In the field of scientific research, whether it is real or fake can be known through communication.
Paper data can be falsified, and papers can be faked or falsified, but there is no way to cheat in communication.
"Mr. Li, the clinical trial plan for this drug has been reported to Director Zheng. Director Zheng said it is okay. Now I need your help to review and approve the budget plan."
When Wang Jinsong reported work to Li Miaomiao, he said that generally the distance between him and Li Miaomiao can be seen from the way he addresses her.
Generally, middle-level and senior executives who have a close relationship with Li Miaomiao will call her "Mr. Miaomiao", while those who have a distant relationship will call her "Mr. Li".
Wang Jinsong was actually recruited by Cheng Gang. He did not resign because the project was not completed and the company was trying to retain him.
But in fact his position is rather awkward.
Li Miaomiao replied: "Okay, you put the document there, I will read it later, and forward a copy of Zheng Li's reply to your email to me."
Zheng Li decides on all matters related to Kechuang Bio's internal research and development, and Li Miaomiao is responsible for all other finance, personnel, sales, manufacturing and other tasks.
Of course, Li Miaomiao will also assign work to other executives. She mainly focuses on personnel and finance.
As long as there are no problems with people and money, an enterprise can maintain a relatively healthy state.
Of course, Zheng Li is in charge here only in the eyes of outsiders. In fact, Zheng Li handed over most of the work to artificial intelligence.
Only a few tasks that cannot be decided by artificial intelligence will be judged by Zheng Li himself.
"Okay, Mr. Li, our innovative drug research and development department will have an overall report meeting next Monday. Minister Wu asked me to invite you to attend. Are you free from 9:30 to 11 a.m. next Monday?"
Li Miaomiao: "Send me the schedule through internal OA. If I am free tomorrow, I will confirm it before Monday."
Every time Wang Jinsong reports work to Li Miaomiao, a sentence always flashes in his heart: choice is more important than hard work.
However, having been in the workplace for so many years, Wang Jinsong knows very well that he has to accept this. The world is inherently unfair, and it has never even been fair. Luck is also a kind of ability.
...
"There have been a lot more unusual incidents in London recently, and we need to step up our search efforts."
"This is not a question of the intensity of the search at all, but when everyone can learn magic, our management methods need to change.
In addition, the anomalies in London are still at the three-digit level. If this level goes up, the anomalies in London can no longer be concealed. "
"The anomalies in London cannot be concealed. Major countries such as America, China, and Russia know everything they need to know.
We now need to judge whether to issue a temporary control order, otherwise there will be more and more magic incidents, and sooner or later the situation will be out of control.
The number of human reviewers on social media such as Facebook, Twitter, and Instagram has increased more than ten times since the end of last year, in order to hide the truth from the public. "
“No, no, no, we are not trying to hide the truth, but to maintain the security and stability of the city.
There would be chaos if people knew that everyone could learn magic, and that spells could only be cast in London.
People from the entire Europa League and even Blue Star will gather in London.
Everyone in London will have no intention of working and just want to learn magic. "
"I am more optimistic than you. It will only have an impact in the short period of time when the news is announced. In the long run, we will return to a stable state.
Well, maybe there will be some twists and turns. "
"There are more and more people in London who can cast spells. If you keep hiding it, there will be a day when you can't.
We need to make a decision as soon as possible, especially the staff around us. After knowing the existence of magic, many privately contacted the captured spell casters in an attempt to learn magic.
In just two months, more than 20 staff members were internally audited for this reason. "
This is a conversation that took place in England's intelligence services.
At this time, three months had passed since Zheng Li deployed the magic network in London.
In these three months, more and more people have learned magic, and then some people have tried to teach magic to their relatives and friends, and many have succeeded.
England officials found themselves losing control of the situation.
The specific reasons for the suspension of flights across London and the detour of routes have been communicated by the Europa Union and major countries in London.
They are now debating whether to reveal the real reason.
Because London Magic is completely different from the Magic Coin system, the threshold is too low.
Everyone can learn it, the only difference is the strength.
The English official believes that this is talent. People who can obtain magic-related information on their own are highly talented. Facts have proved that their spell casting intensity is indeed higher.
Most of the people who learned magic from others have very weak spell-casting strength, and are even no different from ordinary people.
"Of course, we can announce the truth, but have you thought clearly about the consequences of announcing the truth?
Not only will it cause short-term chaos, chaos is acceptable to the big guys above and even the Europa League.
What they cannot accept is that the current situation in London was caused by some powerful magical artifact, and that the magic artifact was lost due to the riots caused by us revealing the cause.
This consequence is something none of us can bear. "
“The question is, isn’t it possible for magic creations to be lost now?
I think the sooner we reveal the truth and get the situation under control, the better for us.
At present, Amerikan has publicly hinted that something is abnormal in London. "
CNN and Fox, two representative American media, have sent special program teams to London.
The euphemistic name is to make a documentary to promote London.
Its true purpose is well known to everyone here.
－－－－－－Digression－－－－－
This chapter has a lot of professional content. Compared with the previous ones, I have tried to compress this part of the content, but sometimes some professional content is needed to make it more realistic. Please forgive me.
