I can extract side effects

Chapter 81 γ-secretase inhibitor, successfully extracted

After sending off Academician Qi, Wei Kang went to the R\u0026D department.

He summoned Chen Yiqing, Wen Renlong and Tang Que, three laboratory leaders, to inform them of the matter.

Then the first one looked at Chen Yiqing and asked.

"Dr. Chen, please speak frankly about your opinion on the task assigned by the superior."

Chen Yiqing frowned, looking over and over at the case in his hand.

After a while, he shook his head and said: "The patient is old and has other diseases such as high blood pressure. Even if we develop a new drug, I can't guarantee the side effects. If the old man takes it, it may cause other diseases. Aggravate."

"And the process of developing a new drug is very long, from identifying the target, to compound synthesis, screening, to safety and toxicity testing, to confirming the way of administration, and finally to clinical trials."

"Even if the elderly can participate in the clinic, it is the last step. The previous procedures will take time, months or years, and no one can guarantee it."

The other two also nodded in agreement.

Wei Kang's heart sank, and he continued to ask: "Then, have you determined the specific research direction? For example, do you start with the elimination of β-amyloid deposition, or start with γ-secretase inhibitors? Or change the direction, start with tau protein Dephosphorylation starts? Even from immune autophagocytes?"

Wen Renlong whistled suddenly, and exclaimed in admiration, "It's ok, thanks to the boss, it seems that you have done a lot of homework, and you are very familiar with these cutting-edge research and development trends."

Wei Kang looked over angrily: "It's business, don't interrupt."

A smile appeared on the corner of Chen Yiqing's mouth, and he continued to introduce the research and development direction of the project.

""Natural Reviews: Drug Discovery" published an article that analyzed the failure of Alzheimer's disease drug development as of 2016. The article included 59 terminated projects in the AD field, 88 research projects and 5 marketed The mechanism of action of the drug is divided into 8 categories, and then the total investment in R\u0026D is calculated based on the number of patients recruited by each mechanism and the consumption of a single patient in each phase of clinical trials."

"The author found that the failed projects mainly focus on the amyloid pathway, Tau protein, neuroimmunity and neurotransmission. The drugs under research mainly focus on amyloid and Tau. 36% of the projects belong to The mechanism is unclear, and there are almost no clinical research projects for mechanisms such as pinocytosis and autophagy.”

"It can be seen that most of the current clinical trials are targeting β-amyloid, trying to break down or prevent the formation of β-amyloid plaques. The project I participated in before at Pfizer is also in this direction."

"β-amyloid protein is the product of γ-secretase hydrolysis of β-amyloid precursor protein (APP). APP can also be hydrolyzed by β-secretase to produce Aβ. Aβ has a strong neurotoxic effect after the accumulation of cell matrix precipitation. Plaque deposition of this type of protein is closely related to the onset of Alzheimer's disease. Many drug developments for Alzheimer's disease also directly target β-secretase or γ-secretase."

"There are many companies involved in the research and development of drugs targeting β-secretase or γ-secretase, and many have entered phase III. For example, β-secretase inhibitors include Merck \u0026 Co. Verubecestat, Lilly Lanabecestat, Biogen Elenbecestat, Johnson \u0026 Johnson Atabecestat, Novartis CNP520 (Umibecestat), γ-secretase inhibitors include Myriad’s Tarenflurbil, Lilly Semagacestat.”

"However, whether it is Merck, Johnson \u0026 Johnson, Novartis' beta-secretase inhibitors, or Eli Lilly's, Myriad's gamma-secretase inhibitors all ended in failure. This is not the first time that amyloid-beta protein has been targeted Failure, and it won't be the last failure."

"Although the new Alzheimer's drug is wiped out, every bit of academic research progress will lay the foundation for subsequent drug development, so we don't need to worry about it, let alone doubt the choice of direction. For the selection of different sites of γ-secretase Differences will also lead to very different results in subsequent clinical development."

"Based on this, we can completely select new protein targets, improve or synthesize new molecular structures of γ-secretase inhibitors, and make them more suitable for the targets, so as to achieve therapeutic effects."

Wei Kang nodded and said, "This is a safe direction."

Chen Yiqing was very encouraged: "At present, we have several pre-selected targets, and new compound molecular formulas have also been constructed and are being improved. When the most suitable one is screened, we can carry out follow-up tests."

Wei Kang approved, and then looked at Tang Que who was beside him. This 1.8 meter tall man was listening seriously at the moment. He had a good student's well-behaved appearance, which made it difficult for him to adapt.

After all, Tang Que's appearance is too tough, burly, muscular, plus a big rough face, with various blue tattoos on his hands, it is unimaginable that a scientific researcher can look like this, but more like a person who came to him A professional killer, when he arrived, the security guard almost called the police.

So he said seriously: "Dr. Chen, Dr. Tang is a molecular biologist. He will help you analyze protein molecules to find suitable targets. If you need help from a computational chemist, Xiaolong can also use molecular dynamics. Dynamically deduce the interaction process between drug molecules and protein molecules on the computer."

"In short, with the cooperation of the three of you, the progress of the project will definitely be accelerated. I am waiting for your good news."

After learning about the direction of new drug research and development, Wei Kang returned to his laboratory.

He began to search the abandoned drug database with ease.

Since the true cause of Alzheimer's disease has not been determined, various research and development directions are based on hypotheses.

Therefore, there are many research and development directions for various new drugs, and he intends to see if there are any suitable side effects that can be extracted.

Maybe there are side effects on the brain, but I don't know if it has any effect.

"Beta-amyloid and tau are deposited in the brain, which can be toxic to neurons and cause brain shrinkage. In this way, there are several directions for research and development."

"The first is secretase inhibitors, which can either enhance the activity of α-secretase or inhibit the activity of β- and γ-secretase, which can effectively reduce amyloid production and achieve therapeutic purposes."

"The second is tau protein as a target, which produces a dephosphorylation effect by increasing the activity of protein phosphatase, and restores abnormal tau protein to normal, thereby achieving therapeutic effects."

"The third is immunotherapy, which allows patients to produce Aβ antibodies in an active or passive manner, thereby delaying or clearing Aβ aggregation in brain tissue. However, there are great risks and uncertainties in this method, and not every patient is Can produce enough antibodies, and the immune response is easy to go too far, leading to aseptic meningitis."

"So there are probably two directions, one is to prevent the deposition of amyloid, and the other is to eliminate the amyloid that has already been deposited."

"If it is blocked, it is a secretase inhibitor. If it is eliminated, it can either synthesize a small molecule drug that can precisely bind to the β-amyloid target to eliminate it, or it can stimulate the activity and quantity of autophagy lysosomes through drug action. , so as to swallow up the amyloid protein and achieve the effect of elimination.”

While thinking, Wei Kang searched for the abandoned prescriptions, looking for side effects related to these aspects.

At first, he searched for drugs to treat encephalitis and cranial nerves.

Because cranial nerve injury is mainly hypoxic-ischemic damage, these drugs have the effect of promoting the recovery of vascular and nerve function.

Unfortunately, the side effects did not satisfy him. They were all alkalosis, hypokalemia, drooling, flushing, vomiting, headache, rapid heartbeat, etc., which were useless.

He had no choice but to hold back his temper and look carefully one by one.

Suddenly, his eyes lit up.

A completely unexpected prescription appeared in front of him.

"A small-molecule drug for the treatment of acne inverse was originally intended to treat hyperkeratosis of hair follicles, but the effect was very poor. After use, it actually exacerbated the deterioration of acne inflammation, so it was abolished."

"Because one of the components with a weak content can inhibit the production of γ-secretase, resulting in the loss of γ-secretase, which can cause a malignant reaction and stimulate the skin to form abscesses."

"It turns out that the lack of γ-secretase can actually lead to this result. Also, acne inflammation occurs more often in young people, and there must be no amyloid deposition in the brain."

"This side effect is exactly what I want."

"System, extract the side effects of inhibiting γ-secretase, and generate new drugs."

It will be on the shelves tomorrow, and today there will be a block chapter three times, which makes people want to cry without tears.

I applied for lifting the ban, but I don't know when it will be fine.

Thank you Meteor Meow for your 100 rewards, and thank you readers for your support.