Overview
explore MoA's pivotal role in drug development and therapy, shaping pharmaceutical science's core principles

Intro

In the past, scientists derived drugs from natural products or were inspired by traditional remedies. Very common drugs, such as paracetamol, known in the US as acetaminophen, were put into clinical use decades before the biological mechanisms driving their pharmacological activities were understood. Today, with the advent of more powerful technologies, drug discovery has changed from the serendipitous approaches of the past to a more targeted model based on an understanding of the underlying biological mechanism of a disease. In this new framework, scientists seek to identify a protein target associated with a disease and develop a molecule that can modulate that protein target. As a shorthand to describe the biological activity of a given molecule, scientists assign a label referred to as mechanism-of-action or MoA for short.

The transition to targeted drug discovery presents both challenges and opportunities in understanding mechanisms of action (MoA). Challenges include the rise of drug resistance and off-target effects, which can hinder therapeutic efficacy. Overcoming these hurdles demands precision in drug design and interdisciplinary collaboration among researchers, clinicians, and industry partners. However, this shift also heralds a new era of personalized medicine, where MoA insights enable tailored treatments based on individual patient profiles. By leveraging genomic sequencing and advanced imaging, healthcare providers can optimize drug efficacy while minimizing adverse effects. Embracing these advancements promises to enhance our understanding of MoA and revolutionize therapeutic interventions in the quest for improved patient outcomes

What is the Mechanism of Action (MoA) of a drug?

In pharmacology, the term Mechanism of Action (MoA) refers to the specific biochemical interaction through which a drug substance produces its pharmacological effect. A mechanism of action usually includes mention of the specific molecular targets to which the drug binds, such as an enzyme or receptor. Receptor sites have specific affinities for drugs based on the chemical structure of the drug, as well as the specific action that occurs there. In contrast, a Mechanism of Action (MoA) describes how a drug works on a molecular level in the body.

Why MOA?

Understanding the mechanism of action of a drug is the most fundamental and thorough way of understanding how it does what it does. This in turn provides information regarding a drug's appropriate use, possible side effects, and possible contraindications.
Mechanism of action fosters a deeper understanding and appreciation of a drug’s potential in treating a disease, driving its progress through the development pipeline.
It is important in order to rationalize phenotypic findings and to anticipate potential side-effects.
By knowing the interaction between a certain site of a drug and a receptor, other drugs can be formulated in a way that replicates this interaction, thus producing the same therapeutic effects. Indeed, this method is used to create new drugs.
In the early stages of the clinical development lifecycle, MoA is critical in demonstrating the value of a drug to investors, collaborators, and regulatory authorities. An in-depth understanding of how your drug works in the body and establishing the unmet need is the foundation for building trust with key stakeholders and investors.

How Mechanism of Action Is Determined With Computational Methods

One approach is to treat a sample of human cells with the drug and then analyze the cellular responses with algorithms that search for similarity to known patterns in large genomic databases, such as libraries of gene expression or cell viability patterns of drugs with known MoAs.

Computation inference methods are primarily used to predict protein targets for small molecule drugs based on computer-based pattern recognition. However, this method could also be used for finding new targets for existing or newly developed drugs. By identifying the pharmacophore of the drug molecule, the profiling method of pattern recognition can be carried out where a new target is identified. This provides an insight at a possible mechanism of action since it is known what certain functional components of the drug are responsible for when interacting with a certain area on a protein, thus leading to a therapeutic effect.

Who Can Use a Drug MoA?