I Just Want to Be a Quiet Top Student

From the route design to the setting of specific experimental steps, C01C did nine synthesis experiments, which took several months, and finally obtained the target product with a total yield of 25%.

It took more than a month to do nine synthesis experiments for four days and three nights at a time.

The route design took three months, three months of thinking, and more than a month of practice, and the chemical trio got the preset product.

Before the route design, there is a large amount of literature search and computer-aided verification, and the time required is difficult to estimate.

"I work in an organic outsourcing company, and I do more than 200 compounds a year. In the center, I estimate that I can make up to three a year." Cheng Haonan said with a lot of emotion, with a feeling of being a man of two lives.

"Where do you want to work?" Shen Qi asked.

"Of course I follow Boss Shen!" Cheng Haonan replied without hesitation, "The work in the center starts from the route design and obtains the target product step by step. This is the real organic chemistry. What we do is scientific research with thought and soul. Work. In outsourcing companies, we do manual labor.”

Lao Yan, who had tasted the sweetness, asked: "The sample of C01C has come out, and the total yield has reached 25%, so our task has been completed? The next step is to write a paper and publish it?"

At that time, C01B achieved this step. Shen Qi asked Lao Yan to write a paper, published it, and then sold the patent.

Shen Qi said: "The task of organic chemistry is completed, and the next step is the work of biochemistry."

"Old Cheng and I don't know much about biochemistry, pharmacology, and pharmacokinetics." Lao Yan revealed the blind spots in his and Cheng Haonan's knowledge reserves.

Shen Qi patted Lao Yan's shoulder: "Yan Gong, what you said is very amateurish, and you can't learn if you don't understand? Don't you two have a master's degree? You have never thought of doing a Ph. D. to recharge your batteries? Biochemistry is interlinked in many places and intersects with each other, and the two of you can go for a Ph.D. in biochemistry or medicinal chemistry."

Lao Yan smiled: "Well, actually, I know a little about biochemistry. After all, I am a top student in the chemistry department. Among the students majoring in chemistry, my biology score is the best."

Cheng Haonan said: "I haven't studied pharmacology and pharmacokinetics systematically, but the outsourcing company I worked for made compounds that were prototypes of drugs, which were actually drug samples that had not been certified and approved. Haven't eaten pork, haven't seen pigs running? I know a little bit too."

Shen Qi: "Oh, you two are really geniuses, you understood it right away? Well, you two worked hard and did the activity experiment of C01C. After the results of the activity experiment came out, you two wrote the paper , who is the corresponding author and who is the first author, you two discuss it yourself."

Both Laoyan and Cheng Haonan knew that C01C was an expected drug.

Glycogen synthase kinase-3β is associated with various diseases, including diabetes, Alzheimer's disease, immune diseases, cancer, etc.

The use of C01C, Shen Qi set it as a glycogen synthase kinase-3β inhibitor.

In fact, scientific research institutions, pharmaceutical companies, and CROs in Europe, the United States, and Japan are all researching glycogen synthase kinase-3β inhibitors, and what has been officially reported is the research results of the Swiss Novartis research team.

The Novartis research team reported a new compound CX017721 three years ago. This compound has a good therapeutic effect on patients with Alzheimer's disease in Phase IIB of European clinical trials.

Three years have passed, and the research team of this Swiss pharmaceutical giant has not continued to report the results of CX017721 in the European phase III clinical trial.

Under the premise that the basic research is recognized, it takes three to five years to develop a new drug, from the initial target setting to the drug launch, which is the speed of light, and ten years is the average speed.

In other fields, the strength of an enterprise's R\u0026D team is hardly comparable to that of a formal scientific research institution.

The only exception is the pharmaceutical industry. There are many Nobel Prize winners in the research and development teams of international pharmaceutical giants.

Shen Qi designed the C01C, and also got some inspiration from the research results of the Swiss Novartis research team.

The Swiss team has been silent for three years, while the chemistry trio of the Chinese Yanda team continued to move forward.

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

"Baki's Kinase-Glo test method, who knows?" Shen Qi asked.

"I will do this, basic practice." Cheng Haonan volunteered, took a 96-well plate and tested it in the buffer solution.

"Old Cheng, it's ok, I should be very skilled in hands." Lao Yan became a spectator.

"The five-year career as an organic migrant worker has been somewhat fruitful. I am not as advanced and in-depth in basic research and route design, but in terms of specific applications and practical skills, I am still good." Cheng Haonan gradually gained some confidence as a scholar. The influence of the environment and the people around you cannot be ignored.

If you mix with migrant workers for scientific research every day, you can be the boss of migrant workers at most.

Working with people who have ideals and pursuits, the view will be farther and more magnificent.

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

Incubate at 30°C for 30 minutes, then terminate the enzyme reaction with Kinase-Glo reagent, and Cheng Haonan completes all operations by himself and records the intensity of chemiluminescence.

The student's hands-on ability is indeed very strong, otherwise he would not be able to be the experimental team leader of an organic outsourcing company.

"The inhibitory mode of the compound is determined by enzyme kinetics experiments, and is also tested based on chemiluminescence. By graphing, the line intersects on the y-axis, the inhibitor is ATP-competitive, and the line intersects on the x-axis, the inhibitor is non-ATP Competitive type. From the experimental data, we can see that the inhibitory effect of C01C neither competes with ATP nor competes with the substrate, so..." Cheng Hao Nankou said a lot, talking about the key position stuck up.

Further discussion will focus on medicinal chemistry, and Cheng Haonan's theoretical reserves are not enough.

The subordinate was stuck, and the leader added, Shen Qi said: "I think, from its double reciprocal figure, it can be inferred that C01C is actually a non-ATP competitive inhibitor. Glycogen synthase kinase-3β inhibitors still need to be verified by medicinal chemistry and biochemistry methods, as well as a series of tests such as animal experiments and clinical experiments."

"The further we advance, the stronger the color of medicine is, and the three of us can't handle it. Our work in the laboratory is over. Let's sort out the data and start writing the paper." Shen Qi made a summary.

When it comes to writing papers, Lao Yan is in high spirits: "I am the best at writing papers."

From the experience of C01B, we can know that after writing a paper and publishing it, you can sell your patent again.

But this time, Shen Qi is not in a hurry to transfer the scientific research results. C01B is a compound that may become a smoking cessation drug, and C01C faces a wider range of people, such as diabetic patients, Alzheimer's disease patients, immune disease patients, There are too many cancer patients.

This benzothiazinone compound may develop into a family like Janssen's classic product fentanyl, and it is a family of drugs with a larger and wider range of applications.

At Shen Qi's level, how could he be unable to distinguish between priorities and the estimated prospects of a scientific research product?

"C01C is no longer for sale, we will continue to carry out subsequent research." Shen Qi said, he had an idea in mind.

"Boss, you also said just now, animal experiments, so many clinical trials, the three of us can't handle it?" Lao Yan asked suspiciously.

"That's right, so we need to make full use of external resources. You two don't need to worry about this matter for the time being. Go ahead and write a thesis and seize the academic commanding heights first. The research results are here. When we have the ability, we will do the latter." work." Shen Qi left after arranging the work in the laboratory.

Lao Yan told Cheng Haonan: "Boss Shen set up an animal laboratory before and recruited Lao Tu to be an animal experimenter. Later, Boss Shen changed his strategy and said that we only do route design and sample synthesis in the laboratory stage. Now, Boss Shen has changed his strategy again, this... Boss' thoughts are really hard to fathom."

"The big boss is like this. When you become a big boss, you will understand."

"You said it as if you were a big boss!"