The Boss's Thoughts

From route design to the setting of specific experimental steps, C01C conducted nine synthesis experiments over several months, finally obtaining the target product with a total yield of 25%.

Nine synthesis experiments were conducted, each lasting four days and three nights, taking more than a month in total.

The route design took three months, three months of thought, and more than a month of hands-on practice. The chemistry trio obtained the expected product.

Before the route design, there was a lot of literature review and Computer Science verification, the time required of which was difficult to estimate.

"I work at an organic outsourcing company, where I process over two hundred compounds a year. At the center, I estimate I can only process a maximum of three a year," Cheng Haonan said with deep feeling, as if he had lived two lives.

"Where would be a better place to work?" Shen Qi asked.

"Of course I'll follow Boss Shen!" Cheng Haonan answered without hesitation. "The work at the center, starting from route design and gradually obtaining the target product, is true Organic Chemistry. We do research with thought and soul. At the outsourcing company, we do manual labor."

Having tasted success, the experienced Old Yan asked, "The C01C samples are ready, with a total yield of 25%, so our task is complete, right? Next, it's time to write the paper and publish it, isn't it?"

When C01B reached this stage, Shen Qi had Old Yan write a paper, published it, and then sold the patent.

Shen Qi said, "The Organic Chemistry part is complete; the next step is the biochemistry work."

"Biochemistry, pharmacology, pharmacokinetics— Old Cheng and I don't really understand those," Old Yan said, pointing out the gaps in Cheng Haonan knowledge.

Shen Qi patted Old Yan on the shoulder. "Yan Gong, what you're saying is very unprofessional. You don't understand and can't learn? Don't you both have master's degrees? Haven't you ever thought about pursuing a doctorate to further your knowledge? Biochemistry is interconnected and interdisciplinary in many areas. You two could totally pursue a doctorate in biochemistry or medicinal chemistry."

Old Yan chuckled, "Well, actually, I know a little bit about biochemistry too. After all, I'm a top student in the chemistry Chemistry Department; among chemistry students, I have the best biology grades."

Cheng Haonan said, "I haven't studied pharmacology or pharmacokinetics systematically, but the outsourcing company I worked for before produced drug prototypes—actually unapproved drug samples. Even if I haven't eaten pork, I've seen pigs run, right? I know a little bit about it."

Shen Qi: "Oh, you two are truly geniuses, understanding it so quickly? Okay, then you two work a little harder and do the C01C activity experiment. After the activity experiment results are in, you two write the paper, and decide between the corresponding author and the first author."

Both Old Yan and Cheng Haonan knew that C01C was a anticipated drug.

Glycogen synthase kinase-3β is associated with a variety of diseases, including diabetes, Alzheimer's disease, immune diseases, and cancer.

Shen Qi defined the purpose of C01C as an inhibitor of glycogen synthase kinase-3β.

In fact, research institutions, pharmaceutical companies, and CROs in Europe, America, and Japan are all researching glycogen synthase kinase-3β inhibitors. The research results of the Novartis have been officially reported.

Three years ago, Novartis' research team reported a new compound, CX017721, which showed promising therapeutic effects in Alzheimer's disease during a Phase IIB clinical trial in Europe.

Three years have passed, and the research team of this Swiss pharmaceutical giant has not continued to report the results of CX017721's Phase III clinical trials in Europe. Perhaps it has not yet reached Phase III, or perhaps it is still in progress, or perhaps it has failed.

Provided that basic research is recognized, developing a new drug, from initial target setting to drug launch, takes three to five years at lightning speed, and ten years is the average speed.

In other fields, the strength of a company's R&D team is difficult to compare with that of a formal research institution.

The pharmaceutical industry is an exception, with many Nobel laureates among the research and development teams of international pharmaceutical giants.

Shen Qi's design of the C01C also drew some inspiration from the research findings of the Novartis research team in Switzerland.

The Swiss team has been silent for three years, while the three-person chemistry team from Yenching University in China continues their work.

The key is the inhibitory activity of C01C on glycogen synthase kinase-3β, and Shen Qi's laboratory has all the basic experimental instruments for activity testing.

"Who knows Baki's Kinase-Glo testing method?" Shen Qi asked.

"I know this, it's basic stuff." Cheng Haonan volunteered and took a 96-well plate to conduct the test in the buffer solution.

"Old Cheng, not bad, that guy has excellent practical skills." Old Yan became a spectator.

"My five years as an organic worker have yielded some results. I'm a bit lacking in basic research and route design, but I'm quite good at specific applications and practical skills." Cheng Haonan gradually gained some scholarly confidence. The influence of the work environment and the people around you on a person cannot be ignored.

If you hang out with research workers every day, you'll at best become the Boss.

Working with people who have ideals and aspirations allows you to see a more distant and magnificent view.

Cheng Haonan skillfully took DMSO solutions of CO1C samples of different concentrations, diluted them with buffer solution, added 2 μL of enzyme solution and buffer solution containing substrate and ATP to each well.

The enzyme reaction was incubated at 30 degrees Celsius for 30 minutes, and then terminated with Kinase-Glo reagent. Cheng Haonan completed all the operations by himself and recorded the chemiluminescence intensity.

This student is indeed very capable; otherwise, he wouldn't have been able to become the lab leader at the organic outsourcing company.

"The inhibitory mechanism of the compound was determined through enzyme kinetic experiments, also based on chemiluminescence assays. By plotting the data, the line intersecting the y-axis indicates an ATP-competitive inhibitor, while the line intersecting the x-axis indicates a non-ATP-competitive inhibitor. Through the experimental data, we can see that the inhibitory effect of CO1C neither competes with ATP nor with the substrate, therefore..." Cheng Haonan spoke fluently for a while, but then stopped at the crucial point.

The discussion then deviates further into medicinal chemistry, where Cheng Haonan's theoretical foundation is insufficient.

When a subordinate hesitated, the Shen Qi added, "I believe that from its double reciprocal graph, we can infer that CO1C is actually a non-ATP-competitive inhibitor. As a new class of glycogen synthase kinase-3β inhibitors with long lipid substitution at position 2, benzothiazinone compounds still need to be verified through medicinal chemistry and biochemistry methods, as well as a series of tests including animal experiments and clinical trials."

"The further we go, the stronger the medical aspects become, and the three of us can't handle it alone. Our work in the lab is finished; let's organize the data and start writing the paper," Shen Qi summarized.

When the topic turned to writing papers, Old Yan became very enthusiastic. "Writing papers is my forte."

As can be seen from C01B's experience, once the paper is written and published, the patent can be sold.

However, Shen Qi is not in a hurry to transfer his research results this time. C01B is a compound that has the potential to become a smoking cessation drug, while C01C is aimed at a much wider range of people, including diabetic patients, Alzheimer's disease, patients with autoimmune diseases, and cancer patients. There are too many to list.

These benzothiazide compounds have the potential to develop into a family, similar to Janssen's classic fentanyl, and even a larger and more widely used family of drugs.

How could someone at Shen Qi's level not be able to distinguish between primary and secondary issues, or fail to see the projected prospects of a research product?

"We're not selling C01C anymore; we'll continue with our research," Shen Qi said, revealing his plans.

"Boss, you just said it yourself, animal experiments, so many phases of clinical trials, can't the three of us handle it?" Old Yan asked doubtfully.

"Yes, that's why we need to make full use of external resources. You two don't need to worry about this for now. Go write your papers and seize the academic high ground first. The research results are right here. We can do the subsequent work whenever we have the capability." After arranging the work in the laboratory, Shen Qi left.

Old Yan said to Cheng Haonan, "Before, Boss Shen set up an animal laboratory and hired Old Tu as an animal experimenter. Later, Boss Shen changed his strategy, saying that we would only do route design and sample synthesis in the laboratory stage. Now, Boss Shen has changed his strategy again. This... it's really hard to fathom what the boss is thinking."

"That's how big shots are. You'll understand when you become a big shot."

"You talk like you've been a big shot before!"