After Wei Kang saw off Academician Qi, he came to the R&D Department.
He summoned the three laboratory leaders, Chen Yiqing, Wen Renlong and Tang Que, to inform each other of the matter.
Then the first one looked at Chen Yiqing and asked.
"Dr. Chen, please frankly express your views on the tasks assigned by the superiors."
Chen Yiqing frowned and turned over the case in his hand.
After a while, he shook his head and said: "The patient is old and has high blood pressure and other diseases. Even if we develop a new drug, I can't guarantee what the side effects will be. If the elderly take it, it may cause other diseases. Aggravated."
"And the process of developing a new drug is very long, from identifying the target, to compound synthesis, screening, to safety and toxicology testing, to confirming the administration method, and finally to clinical trials."
"Even if the elderly can participate in clinical trials, it is the last step. The previous procedures will also take time, months or years. No one can guarantee it."
The other two people also nodded in agreement.
Wei Kang's heart sank and he continued to ask: "Then have you determined the specific research direction? For example, should you start with eliminating β-amyloid deposition, or start with γ-secretase inhibitors? Or change the direction, start with tau protein Dephosphorylation starts? Even starting with immune autophagy cells?"
Wen Renlong suddenly whistled and exclaimed: "Okay, you are the boss. It seems that you have done a lot of homework and are very familiar with these cutting-edge research and development trends."
Wei Kang looked over angrily: "We're talking about business, don't interrupt."
Chen Yiqing showed a smile and continued to introduce the research and development direction of the project.
"Nature Reviews: Drug Discovery once published an article analyzing the failed Alzheimer's disease drug development as of 2016. The article listed 59 terminated projects, 88 ongoing projects and 5 marketed projects in the AD field. The mechanism of action of the drug is divided into 8 categories, and then the total R&D investment is calculated based on the number of patients recruited for each mechanism and the consumption of a single patient in each clinical phase."
"The author found that the failed projects were mainly concentrated in the amyloid pathway, Tau protein, neuroimmunity and neurotransmission. The drugs under development were mainly concentrated in amyloid and Tau. 36% of the projects were The mechanism is unclear, and there are almost no clinical research projects on mechanisms such as pinocytosis and autophagy."
"It can be seen that most of the current clinical trials are targeting β-amyloid protein, trying to break down or prevent the formation of β-amyloid plaques. The project I participated in before at Pfizer was also in this direction."
“Beta-amyloid is the product of beta-amyloid precursor protein (APP) hydrolyzed by γ-secretase. APP can also be hydrolyzed by beta-secretase to produce Aβ. Aβ has a strong neurotoxic effect after precipitation and accumulation in the cell matrix. 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 β-secretase or γ-secretase target drugs, and many have entered Phase III. For example, β-secretase inhibitors include Merck Verubecestat, Eli Lilly Lanabecestat, Biogen Elenbecestat, Johnson & Johnson Atabecestat, Novartis CNP520 (Umibecestat), Myriad’s Tarenflurbil, Eli Lilly’s Semagacestat that inhibits γ-secretase.”
“However, both the β-secretase inhibitors from Merck, Johnson & Johnson, and Novartis, and the γ-secretase inhibitors from Eli Lilly and Myriad, all ended in failure. This is not the first time that β-amyloid has been targeted. Failure will not be the last failure.”
"Although all new Alzheimer's drugs have been wiped out, every bit of academic research progress will lay the foundation for subsequent drug development, so we don't need to worry unfounded, let alone doubt the choice of direction. Regarding the selection of different sites of γ-secretase Differences will also lead to very different results in subsequent clinical development."
"On this basis, we can completely select new protein targets, improve or synthesize new γ-secretase inhibitor molecular structures to make them more suitable for the target, thereby achieving therapeutic effects."
Wei Kang nodded and said, "This is a safe direction."
Chen Yiqing is encouraged: "Currently we have several pre-selected targets, and new compound molecular formulas have been constructed and are being improved. Once the most suitable ones are screened out, follow-up testing can be carried out."
Wei Kang looked approvingly, and then looked at Tang Que, who was standing aside. The 1.8-meter-tall tall man was listening carefully at the moment, with the obedient appearance of a good student, which made it difficult for him to adapt.
After all, Tang Que's appearance is too tough, with a burly body, bulging muscles, a big, rough face, and various green tattoos on his hands. It is unimaginable that a scientific researcher can look like this. Instead, he looks more like a person who came to the door. The professional killer was so frightened that the security guard almost called the police when he arrived.
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 full cooperation of the three of you, we will definitely be able to speed up the progress of the project. I'm looking forward to 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 yet been determined, various research and development directions are currently based on hypotheses.
Therefore, there are many directions for the development of various new drugs, and he plans to see if there are any suitable side effects that can be extracted.
Maybe it has side effects on the brain, but I don’t know if it has any effect.
"Beta-amyloid and tau proteins are deposited in the brain, which poisons neurons and causes brain atrophy. In this way, there are several research and development directions."
"The first one is a secretase inhibitor, which either enhances the activity of α-secretase or inhibits the activities of β- and γ-secretase, both of which can effectively reduce the production of amyloid and achieve therapeutic purposes."
"The second is tau protein as a target, which produces a dephosphorylation effect by increasing protein phosphatase activity, returning abnormal tau protein to normal, thereby achieving a therapeutic effect."
"The third type is immunotherapy, which uses active or passive methods to allow patients to produce Aβ antibodies, thereby delaying or clearing Aβ aggregation in brain tissue. However, this method involves great risks and uncertainties, and not every patient can Can produce enough antibodies, and the immune response can easily be excessive, leading to aseptic meningitis."
"So there are probably two directions, one is to prevent the deposition of amyloid protein, and the other is to eliminate the amyloid protein that has already been deposited."
"If it is blocked, it is a secretase inhibitor. If it is eliminated, either small molecule drugs can be synthesized and precisely combined with the β-amyloid target to eliminate it, or the activity and number of autophagy lysosomes can be stimulated through the action of drugs. , thereby swallowing up the amyloid protein and achieving the effect of elimination."
While Wei Kang was thinking, he searched for abandoned prescriptions, looking for side effects related to these aspects.
Initially, he searched for drugs to treat encephalitis and cranial nerves.
Because cranial nerve damage is mainly hypoxic-ischemic damage, these drugs have the effect of promoting the recovery of vascular and neurological functions.
Unfortunately, the side effects did not satisfy him. They were alkalosis, hypokalemia, drooling, blushing, vomiting, headache, rapid heartbeat, etc., etc., which were of no use.
He had no choice but to be patient and look through each one carefully.
Suddenly, his eyes lit up.
A completely unexpected prescription appeared before him.
"A small molecule drug for the treatment of paradoxical acne was originally intended to treat hair follicle hyperkeratosis, but the effect was very poor. After use, it actually aggravated the acne inflammation, so it was abolished."
"Because one of the weak components can inhibit the production of gamma secretase, leading to the lack of gamma secretase, causing malignant reactions and stimulating the formation of abscesses on the skin."
"It turns out that the lack of γ-secretase can actually lead to this kind of result. Also, acne is more likely to occur in young people, so there must be no amyloid deposition in the brain."
"This side effect is exactly what I want."
"The system extracts the side effects of inhibiting gamma secretase and generates new drugs."
