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Drug Discovery: Overview

Drug Discovery: Overview

Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...

Covalent Bonds

Covalent Bonds

Covalent Bonds

Covalent Bonds

Overview
When two atoms share electrons to complete their valence shells, they create a covalent bond. An atom's electronegativity—the force with which shared electrons are pulled towards an atom—determines how the electrons are shared. Molecules formed with covalent bonds can be either polar or nonpolar. Atoms with similar electronegativities form nonpolar covalent bonds; the electrons are shared equally. Atoms with different electronegativities share electrons unequally,...

Network Covalent Solids

Network Covalent Solids

Network covalent solids contain a three-dimensional network of covalently bonded atoms as found in the crystal structures of nonmetals like diamond, graphite, silicon, and some covalent compounds, such as silicon dioxide (sand) and silicon carbide (carborundum, the abrasive on sandpaper). Many minerals have networks of covalent bonds.
To break or to melt a covalent network solid, covalent bonds must be broken. Because covalent bonds are relatively strong, covalent network solids are typically...

Covalently Linked Protein Regulators

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....

Covalently Linked Protein Regulators

Covalently Linked Protein Regulators

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Related Experiment Video

Updated: Jan 27, 2026

Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling

Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling

Published on: March 20, 2018

Covalent binders in drug discovery.

Anil Vasudevan¹, Maria A Argiriadi², Aleksandra Baranczak¹

¹AbbVie Inc., North Chicago, IL, United States.

Progress in Medicinal Chemistry

|March 19, 2019

Summary

Covalent binders offer new therapeutic and biological probe possibilities. Researchers are advancing methods to control their reactivity for targeted applications, including in antibody drug conjugates.

Keywords:

Activity-based protein profiling Antibody drug conjugates Bioorthogonal chemistry Computer aided drug design Covalent drugs Photoaffinity labelling Targeted covalent inhibition

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Area of Science:

Medicinal Chemistry
Chemical Biology
Drug Discovery

Background:

Covalent modulation of protein function presents therapeutic and biological probe opportunities.
Despite historical skepticism regarding toxicity, significant advancements have been made in understanding and controlling covalent interactions.
Covalent binders are increasingly recognized for their potential in uncovering novel biological pathways and as effective payloads in antibody drug conjugates.

Purpose of the Study:

This perspective aims to elucidate the fundamental principles of covalent binders.
To review the diverse applications of covalent modulation in biological and therapeutic contexts.
To highlight the progress in harnessing covalent interactions for targeted therapies and biological research.

Main Methods:

This perspective synthesizes current knowledge on covalent binder design and application.
It reviews literature on tuning electrophilicity for selective residue targeting.
The discussion includes the use of covalent binders in antibody drug conjugates and biological probes.

Main Results:

Significant progress has been achieved in understanding how to tune electrophilicity for selective covalent modification of protein residues.
Covalent binders are proving valuable in discovering new biological mechanisms and enhancing antibody drug conjugate efficacy.
The field is moving beyond toxicity concerns towards precise and beneficial applications.

Conclusions:

Covalent modulation of protein function holds substantial promise for therapeutic development and biological interrogation.
Continued research into controlling reactivity is key to overcoming toxicity concerns and maximizing utility.
Covalent binders represent a powerful and evolving toolset in modern drug discovery and chemical biology.