| Customer Validation |
| Covalent Drugs are a class of small molecule compounds that can covalently bind to specific target proteins, activating/inhibiting their corresponding signal pathways’ functions. They have a history of treating diseases for over a century, it could date back to the nonsteroidal anti-inflammatory drug aspirin in the late 17th century. Compared to non-covalent drugs, covalent drugs have the advantages of enhancing drug potency, prolonging target binding time, more robust selectivity, and the ability to target some “undruggable” targets, addressing drug resistance issues. So far, covalent drugs have accounted for about 30% of the drugs on the market. |
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| Figure 1. Covalent Drugs Development History[1]. |
| Mechanism of Action of Covalent Drugs |
| The process of covalent binding of their targets involves two key steps. The first step is the reversible binding of the electrophilic warhead of the covalent drug to the biological target through active amino acid residues. The second is the reaction of the drug with the target, leadding to the formation of a covalent bond. This reaction’s reversibility is the basis for the calssification of covalent drugs into reversible and irreversible[2]. |
| Design of Covalent Drugs |
| The design of covalent drugs first requires identifying and validating biological targets, followed by characterization and structural optimization of identified compounds to obtain lead compounds. Covalent drug discovery uses similar methods in traditional medicinal chemistry, including high-throughput screening, FBDD (Fragment-based drug discovery), DEL (DNA Encoded Compound Library) technology, virtual screening, rational drug design, etc. However, there are also unique ways to design covalent drugs (such as target selection, choice of electrophilic warheads, amino acid residues, etc.). |
| MedChemExpress — Master of Bioactive Molecules |
| To accelerate the development of the covalent drug field, MedChemExpress has carefully designed various compound libraries. These compound libraries not only help develop covalent drugs but are also important tools for studying covalent mechanisms. |
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MedChemExpress Covalent Drug Development Compound Libraries |
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| Product Name |
Description |
| Covalent Screening Library |
This Library includes over 1,600+ small-molecule compounds, encompassing both known covalent compounds and compounds with covalent reactive groups, such as acrylamide, activated terminal alkynes,
sulfonyl fluorides/esters, and chloroacetamides. It is a valuable tool for screening covalent compounds and studying the mechanisms of covalent action. |
Covalent Screening Library
Plus |
This Library includes over 3,000+ small-molecule compounds, which serve as a supplement to the MedChemExpress Covalent Compound Library. It adds a number of fragment molecules with covalent warheads, thereby enhancing the screening capabilities. |
Cysteine Targeted Covalent
Library |
This Library includes over 4,500+ small-molecule compounds with various cysteine-targeting covalent warheads. This Library is primarily designed using the following covalent warheads: Acrylamides, Propiolic acid esters, Dimethylamine functionalized acrylamides, etc. |
Cysteine Targeted
Covalent Fragment Library |
This Library includes more than 3,000+ fragment compounds with different cysteine-targeting covalent warheads. The covalent warheads include Acrylamides, Propiolic acid esters, and Dimethylamine functionalized acrylamides. All fragments adhere to the RO3 principle and can be used for fragment-based covalent drug design. |
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References: |
[1] Nat Rev Drug Discov. 2022;21(12):881-898.
[2] Biochemistry. 2019;58(52):5234-5244. |
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