Preclinical and clinical research of new drugs

In 10 years, it has spent 1 billion US dollars to develop a new drug. Whether it is driven by profit or the sense of accomplishment in saving thousands of patients, this behavior of pharmaceutical companies deserves our respect.

What process does a new drug go through from research and development to market launch? What experience can we learn from each step? This article takes small-molecule drugs as an example, and I tried to sort it out. I hope it can be helpful to you.

Research and development (generally 2-3 years)

Laboratory research to find new compounds with potential for the treatment of specific diseases.

1.Discovery and confirmation of drug targets

This is the starting point of all work. Only when the target is determined can all subsequent work have a basis for unfolding.

2.Compound screening and synthesis

According to the spatial structure of the target, a series of matching molecular structures are screened from the virtual compound library, and these compounds are synthesized. They are called lead compounds.

3.Validation and optimization of active compounds

Not all lead compounds can meet the requirements. At this stage, it is necessary to pass in vitro cell test verification to initially screen out compounds with high activity and low toxicity, and optimize the structure according to the structure-activity relationship. These compounds are called drug candidates.

At the same time, there is also a case where a compound has no effect on the target A, but it may have very good activity on other B and C targets. I will not show it for the time being.

Pre-clinical experiment (usually 2-4 years)

The purpose of this stage is to evaluate the pharmacological and toxicological effects of drugs, the absorption, distribution, metabolism and excretion of drugs (ADME). The second is to conduct research on production technology, quality control, and stability (CMC).

The first part of the experiment needs to be carried out at the animal level, and sometimes the results of cell experiments and live animal experiments are quite different. The purpose of this step is to determine the effectiveness and safety of the drug.

The second part needs to be completed in a workshop that meets GMP requirements.

1.Pharmacology Research

Including: pharmacodynamics, pharmacokinetics

2.Toxicology Research

Acute toxicity, chronic toxicity, reproductive toxicity, carcinogenic, teratogenic, and mutagenic conditions

3.Formulation development

You can’t just pour some compounds into your mouth. Formulation development is an important part of drug application. For example, some medicines are poorly absorbed orally and need to be developed as injections.

Some medicines lose their activity in gastric acid, so they need to be developed as enteric-coated preparations.

Some compounds have poor solubility, which can also be partially solved by formulations.

Others need to be administered locally, and they need to be developed into aerosols, ointments, etc. through preparations.