As a mage, I just want to pursue the truth

Chapter 274 Small Biological Molecule Drugs

Under Zheng Li's hands, the research and development pressure is huge, because he understands this industry so well.

The boss is the person who knows the most in the entire R&D field. Your R&D progress, R&D difficulty and R&D ideas can't fool him at all.

For example, Li Wanqing didn't dare to fool Zheng Li at all. He reported on the progress of what he did and didn't do, and reported on his work according to the actual situation.

Among them, Kechuang Biotech will carry out clinical trials of two small-molecule drugs this year. One of the project leaders, Wang Jinsong, is a relatively early research and development personnel in the company's innovative drug research and development field.

He is an alumnus with Cheng Gang, not the same class.

Back then, Kechuang Bio’s listing prospectus stated that it would engage in research and development of original drugs. After the successful listing, Wang Jinsong joined Kechuang Bio.

He has been at Merck before, from Merck's headquarters in New Jersey to Merck East China.

The reason why I came to Kechuang Biology is also because there is almost no room for advancement in Merck.

Coming to Kechuangbiology, there is Cheng Gang. The history of Kechuangbio is very new, the cash flow is abundant, the founder team seems ambitious, and there are many opportunities.

So Wang Jinsong joined Kechuang Bio after resigning from MSD, responsible for the research and development of small molecule drugs.

After joining the job, it is to choose a topic, and then establish a project for research and development.

Wang Jinsong originally thought that Zheng Li didn't know much about the research and development of small molecule drugs.

First of all, it is necessary to popularize a concept of science, that is, drug research and development is divided into many fields, mainly divided into chemical small molecule drugs and biological macromolecular drugs.

Endorphins are biological macromolecules, substances that are inherent in living organisms, but Zheng Li has researched the manufacturing process of endorphins.

Biomacromolecules have larger molecular weights and more complex structures, with molecular masses generally ranging from 1500 to 150000.

The molecular mass of small molecule drugs is generally distributed between 200-700.

Historically, starting from the discovery of penicillin in the 30s and 1982s, until [-], all drugs in the sense of modern medicine were small molecule drugs.

Penicillin is also a small molecule drug.

The first real macromolecule drug was launched in 1982.

The reason for this phenomenon is that the means to determine the structure of small molecules only need NMR-C-C and LCMS to achieve better results.

The means to measure the structure of macromolecules are often more complicated.

Higher precision and sensitivity than small molecules are required in the measurement of biomolecules.

Of course, this does not mean that the research and development of biomacromolecules is absolutely higher than that of compound small molecules.

The most important means of modern small molecule drug development is screening.

To screen, you must first have a sieve, and secondly, you must have a library with enough things in it for you to sieve, and then you need to know what these things in the library are, what they look like, and finally what you sift out. To be able to mass produce.

In recent years, there are also new methods, and the research and development of small molecule drugs of Science and Technology Biotech adopts new technical means.

But historically, especially in the 90s when the pharmaceutical industry was booming, the screening method was the mainstream of the mainstream.

Sieve refers to experiments based on various disease indicators, and small chemical molecules are put into corresponding experiments to see which ones are effective.

The so-called library refers to the molecular library, due to the rapid development of organic synthesis methods in the 80s and [-]s of the last century.

A large number of complex, stable, and heterocyclic molecules, which were originally difficult to synthesize, began to appear in batches.

Advances in detection methods such as nuclear magnetic resonance and mass spectrometry have led to the successful separation of many natural products, which in turn have promoted the synthesis of other types of molecules.

Therefore, by the 90s, there were millions of different types of small molecules in the molecular libraries of various pharmaceutical companies.

The development of biotechnology during this time has led to the discovery of some important disease indicators and targets.

These discoveries led to the ability of biopharmaceutical giants to use millions of small molecules in their hands to screen these diseases and targets, which in turn led to the explosion of new drugs in the 90s.

The distance between Huaguo biopharmaceutical companies and the world's pharmaceutical giants was mainly opened during this period.

While others are doing targeted analysis, domestic progress in this area has been slow.

There is a data that can indirectly prove this point, that is, in 1985, Huaguo began to implement a new drug registration method.

In the 1985 years from 2008 to 23, there were only 5 Class I new drugs approved in Huaguo.

The first time Wang Jinsong heard the name Zheng Li was on "nature", when he was still at Merck's headquarters.

At that time, many people were discussing that the laboratory preparation method of endorphin was researched 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 instead.

The more people in the industry, the more they understand the difficulty of developing biomacromolecular drugs, even if this biomacromolecule is a polypeptide substance that exists in the organism itself.

But if the substances discovered in the 50s are so easy to manufacture, how can they be left for you to discover.

Including Wang Jinsong’s internal historical documents in Merck, he has seen that in the 80s, Merck’s internal R&D team spent two years without solving this problem.

Later, when I learned about Zheng Li, it was when Zheng Li developed an industrial-scale manufacturing method for endorphins, and Kechuang Bio started patent licensing negotiations with major international pharmaceutical companies around endorphins.

Only then did Wang Jinsong believe that there were such geniuses in the world.

Because it is possible to buy a nature paper, but it is impossible to let others sell the industrial manufacturing method.

Especially after the clinical data of endorphins came out, it was almost able to crowd out morphine drugs as drugs that could not fight back.

No one would be generous enough to sell such a huge benefit.

Later, Wang Jinsong joined Kechuang Bio, and Zheng Li went to Lion City not long after he joined.

But every time through remote video conferences, Zheng Li's views and ideas on small molecule drugs give him a feeling of enlightenment.

"Dong Zheng, we intend to use a dual fluorescent cell cycle reporter system to label cells in the mitotic S-G2-M phase and then display cytokinesis.

In addition, a high-throughput screening system was constructed, and 13 small molecules that could effectively induce cardiomyocytes to enter the cell cycle were screened out from the chemical small molecule library.

Except for MCT1 inhibitors, other single small molecules cannot induce cardiomyocyte cytokinesis. "

"You can try to verify the efficacy of the drug by combining small molecules in pairs or more.

Also remember to build mathematical models to predict the best combination of small molecules to promote proliferation.I will send you a mathematical model I built before, and you can refer to my design ideas. "

Wang Jinsong and his group mainly intend to make small molecule drugs for cardiovascular diseases.

Later, according to Zheng Li's thinking, Wang Jinsong and his colleagues discovered through in vitro and in vivo experimental verification that they found a small molecule combination 1SM composed of phenylephrine hydrochloride, baricitinib, dehydrohalamine, PTEN inhibitors and MCT5 inhibitors. , successfully induces cell cycle re-entry and cytokinesis in adult mouse and human cardiomyocytes.

In other words, it can promote heart regeneration and treat myocardial infarction.

(The above research ideas come from a paper published in the CELL sub-journal by the School of Chemistry and Molecular Science, Yenching University in April this year:
"A small-molecule cocktail promotes mammalian cardiomyocyte proliferation and heart regeneration")
Then they established a mouse model of myocardial infarction 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 dedifferentiated state and then enter a proliferative state.

5SM promotes the conversion of cardiomyocyte metabolism from oxidative phosphorylation to glycolysis by activating lactate signaling and mTOR pathways, and finally induces cardiomyocyte proliferation and division.

Zheng Li has a better understanding of small molecule drugs than he does.

This made Wang Jinsong doubt life.

You must know that he started studying biology as an undergraduate, and spent 17 years from undergraduate to post-doctorate. Later, he worked for Merck for another eight years, and spent more than 20 years in the research and development of small molecule drugs in his life.

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 a real cow or a fake cow, you can know it after a chat.

The data of the paper can be falsified, the paper can find a way to name or fake the paper, but there is no way to cheat in communication.

"Mr. Li, the clinical trial plan for this drug has been reported to Chairman Zheng, and Chairman Zheng said yes, and now I need your help to review and approve the budget plan."

When Wang Jinsong reported to Li Miaomiao, he said that generally, the way of addressing Li Miaomiao can tell the distance between him and her.

Generally, middle-level and executives who are close to Li Miaomiao will call her "Mr. Miaomiao", while those who are far away will call her "Mr. Li".

Wang Jinsong was actually recruited by Cheng Gang. Because the project was not completed and the company retained him, he did not leave.

But in fact his position is rather awkward.

Li Miaomiao replied: "Okay, you put the file there, I will read it later, and forward a copy of Zheng Li's reply to your email to me."

Li Miaomiao is in charge of all other financial, personnel, sales, manufacturing and other work related to the internal research and development of Kechuangbio.

Of course, Li Miaomiao will also distribute the work to other executives. She mainly focuses on personnel and finance.

As long as there are no problems with people and money, enterprises 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 jobs that artificial intelligence cannot make decisions will be judged by Zheng Li himself.

"Okay, and 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 09:30 to [-]:[-] next Monday?"

Li Miaomiao: "You send me the schedule through internal oa. If I am free tomorrow, I will confirm it before Monday."

Every time Wang Jinsong reported his work to Li Miaomiao, a sentence always flashed in his heart: choice is more important than hard work.

However, having been in the workplace for so many years, Wang Jinsong knows that to accept this, the world is inherently unfair, and it has never been fair. Luck is also a kind of ability.

"There have been a lot of abnormal incidents in London recently, and we need to increase our search efforts."

"This is not a question of the strength of the search at all, but that when everyone can learn magic, our management methods need to be changed.

In addition, the anomalies in London are currently maintained at the three-digit level. If this level goes up, the anomalies in London can no longer be concealed. "

"The anomaly in London can't be concealed. Major countries like American, Huaguo, and Russia know what they should know.

We now need to judge whether to issue a temporary control order, otherwise there will be more and more magical incidents, and sooner or later the situation will be out of control.

The number of manual auditors on social media such as FB, Twitter, and ins has increased by more than ten times compared to the end of last year, in order to conceal the truth from the public. "

"No, no, we are not here to hide the truth, but to maintain the safety and stability of the city.

There would be chaos if people knew that everyone could learn magic and that it could only be cast in London.

People from the entire Europa League and even Blue Star will gather in London.

Everyone in London will not be interested in working, just want to learn magic. "

"I'm more optimistic than you, it's just that the news will be affected in a short period of time, and in the long run we will return to a stable state.

Well, maybe there will be some bumps and turmoil. "

"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 hide it.

We need to make a decision as soon as possible, especially the staff around us. After knowing the existence of magic, many spellcasters who have been arrested in private contact are trying to learn magic.

In just two months, more than [-] staff were internally audited for this reason. "

This is a conversation that took place in England's intelligence agencies.

At this time, three months have passed since Zheng Li placed the magic net in London.

During these three months, more and more people learned magic, and some people tried to teach magic to their relatives and friends, and there were not a few who succeeded.

England officials found themselves on the verge of losing control of the situation.

The specific reason for the suspension of flights in London and the detour of the route has been communicated with major countries by the Europa Union in London.

They are now debating whether to announce the real reason.

Because London magic is completely different from the magic coin system, the threshold is too low.

Anyone can learn it, the only difference is the power.

Officials in England believe that this is talent, and those who can rely on themselves to obtain magic-related information are highly talented, and it turns out that their spellcasting strength is indeed higher.

However, most of the people who learned magic from others had very weak casting power, and were no different from ordinary people.

"Of course, we can announce the truth, but have you thought about the consequences of announcing the truth?

Not only will it cause short-term chaos, chaos is acceptable to the big figures above and even the Europa League.

What they can't accept is that if the current state of London is caused by some powerful magical artifact, and the riots caused by our announcement of the cause cause the loss of that magical artifact.

The consequences are ones that none of us can afford. "

"The question is, is it impossible for magic creation to be lost now?
I think the sooner we get the truth under control, the better for us.

At present, American has publicly hinted that London is abnormal. "

CNN and FOX, the two representative American media, have sent special program groups to London.

The euphemistic name is to make a documentary to promote London.

Its true purpose is well known to everyone present.

　This chapter has a lot of professional content. Compared with the previous ones, I have tried to compress this part of the content as much as possible, but sometimes some professional content is needed to make the novel more real, please forgive me.

　　
　
(End of this chapter)