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The mysterious power of drugs: How to uncover the secrets of drug mechanisms of action?
In pharmacology, the term "mechanism of action" (MOA) refers to the specific way in which a drug substance produces its pharmacological effect through specific biochemical interactions. A drug's mechanism of action usually refers to a specific molecular target, such as an enzyme or receptor, to which the drug binds. These receptor sites have specific affinities for drugs, based on the drug's chemical structure and the specific action that occurs there. In contrast to drugs that produce therapeutic effects by binding to receptors, some drugs do not bind to receptors, but instead produce corresponding therapeutic effects by interacting with chemical or physical properties in the body. Common examples include antacids and laxatives.
Elucidation of the mechanism of action is crucial in drug development, especially the development of anti-infective drugs. Understanding the interaction between drugs and specific targets can predict clinical safety issues and thus effectively improve the safety of drugs.
The elucidation of the mechanism of action of a drug is important in many ways. First, during the development of anti-infective drugs, the availability of information can predict problems related to clinical safety. For example, drugs that cause disruption of the cell membrane or the electron transport chain are more likely to cause toxicity issues than drugs that target cell wall components or the 70S ribosome, which do not exist in human cells. Understanding the interaction between specific drugs and receptors allows other drugs to be prepared in a similar manner to produce the same therapeutic effect, which has become one of the important methods for creating new drugs. In addition, such research methods can help determine which patients are most likely to respond to treatment.
For example, the breast cancer drug trastuzumab targets the HER2 protein, so medical institutions can screen tumors for the presence of this molecule to determine whether patients will benefit from trastuzumab treatment.
In clinical applications, this knowledge could allow for more precise dosing of drugs, as physicians could monitor the drug based on its effect on the target pathway. Taking statins as an example, their dosage is often determined by measuring the patient's blood lipid levels. By understanding the mechanisms of action of drugs, doctors can also more effectively combine multiple drugs to reduce the likelihood of drug resistance. Knowing the cellular structures on which anti-infective or anti-cancer drugs act could allow doctors to administer multiple drugs simultaneously to inhibit multiple targets, thereby reducing the risk of drug resistance and treatment failure caused by single mutations in microbial or tumor DNA.
Not only that, it may also be possible for the drug to find other indications. Take sildenafil as an example. Its mechanism of action is to inhibit the phosphodiesterase-5 (PDE-5) protein, which allows this drug to be successfully reused for the treatment of pulmonary arterial hypertension because PDE-5 plays a key role in pulmonary arterial hypertension. pulmonary expression.
Methods for determining the mechanism of action of a drug
There are many methods for determining the mechanism of action of a drug, which can generally be divided into several major technical pathways, including microscopy, direct biochemical methods, computational inference methods, and pan-OMIX technology.
Microscopy methods
The phenotypic changes of target cells induced by bioactive compounds can be observed under a microscope, and these changes help to understand the mechanism of action of the compounds. For example, in the case of antibacterial agents, the transformation of target cells into spheroids could indicate inhibition of peptidoglycan synthesis, whereas the filamentation of target cells could indicate perturbations in PBP3, FtsZ, or DNA synthesis. Observation of these changes provides important clues to understanding the mechanism of action of new drugs. Although it currently takes a long time to manually generate and interpret the data, this problem may be solved with the advancement of automated microscopy and image analysis software.
Direct biochemical method
Direct biochemical methods involve labeling certain proteins or small molecules and tracking their dynamics in vivo, which is the most direct way to find small drug targets. By labeling the physical interactions between molecules and proteins, these biochemical methods can be used to determine the toxicity, efficacy, and mechanism of action of drugs.
Calculation and inference methods
Computational inference methods are mainly used to predict protein targets of small molecule drugs based on computer pattern recognition. However, the approach could also be used to find new targets for existing or newly developed drugs. By identifying the pharmacophore of a drug molecule, pattern recognition profiling can be performed, which can help provide insights into the mechanism of action.
All Omix Technology
The All-OMIX technology uses chemical proteomics, reverse genetics and genomics, transcriptomics and proteomics to identify potential targets. This approach utilizes gene perturbation (e.g., CRISPR-Cas9 or siRNA) in combination with a compound to determine whether its knockdown or knockout abolishes the compound’s pharmacological effects. Through these methods, hypotheses about mechanisms of action can be formed and then tested.
Drugs with known mechanisms of action and drugs with unknown mechanisms of action
The mechanisms of action of many drugs have been identified, such as aspirin. The mechanism of action of aspirin involves irreversible inhibition of cyclooxygenase, thereby inhibiting the production of prostaglandins and thromboxanes, reducing pain and inflammation. However, there are also some drugs whose mechanisms of action remain unknown. Even so, these drugs still work, but the specific mechanism by which they interact with the receptors and produce their therapeutic effects is unknown or unclear.
SummaryAlthough the terms "mechanism of action" and "mode of action" are sometimes used interchangeably, they differ in the level of detail they convey. Mode of action describes the functional or anatomical changes that occur at the cellular level after an organism is exposed to a substance, while mechanism of action focuses more on how the drug affects the interaction pattern of enzymes or receptors. Understanding the secrets behind the mechanisms of action of these drugs will not only promote the development of new drugs, but may also provide more precise treatment strategies in clinical practice. In the face of future drug development, can we expect more unknown drug mechanisms to be uncovered?
