molecular interaction

POI (Protein of Interest) refers to the target protein, namely the disease-causing protein or key functional protein that undergoes degradation or functional modulation in molecular glue-mediated processes. The Molecular Glue POI Library consists of a series of fragments that can specifically bind to different types of POIs. As key components of molecular glues, these ligands form stable interactions with target proteins, laying the foundation for molecular glues to induce the interaction between POIs and E3 ubiquitin ligases. The covered POIs include various types such as cancer-associated GSPT1, androgen receptors, and abnormally aggregated proteins linked to neurodegenerative diseases.

This fragment library can be applied to the screening and optimization of targeted protein degraders. By screening ligands with high affinity and strong selectivity for specific POIs from the library, core structures can be identified to develop novel molecular glues. For instance, optimization of ligands targeting GSPT1 has yielded molecular glue degraders with enhanced degradation activity. Since many POIs are difficult to drug due to the lack of traditional small-molecule binding pockets, some ligands in the POI Ligand Library can modulate such POIs by inducing protein-protein interactions, thereby further expanding the scope of drug discovery for undruggable targets.

MCE has compiled a POI Fragment Library comprising thousands of POI fragments with molecular weights ranging from 150 to 400. This compound library can be widely applied in Molecular Glue research and development.

Targeted protein degradation(TPD) is a novel and promising approach to new drug discovery and development. It shows great potential for treating diseases with “undruggable” pathogenic protein targets and for overcoming drug resistance. Molecular glues and PROTACs are both targeted protein degraders that have attracted the most attention.

Molecular glues are small molecular degraders that mainly induce novel interaction between an E3 ligase and a target protein to form a ternary complex, leading to protein ubiquitination and subsequent proteasome degradation. Compared with PROTACs, molecular glues generally possess more favorable drug-like properties, such as lower MW, higher cell permeability, and better oral absorption. Molecular glues are emerging as a promising new therapeutic strategy.

MCE supplies a unique collection of 105 molecular glues which target various proteins. MCE Molecular Glue Compound Library is a useful tool to conduct scientific research and disease mechanism study.

Targeted Protein Degradation (TPD) is a novel and promising approach to drug development. It shows great potential for targeting proteins traditionally considered "undruggable" due to the lack of enzymatic function and absence of binding sites by tagging them for degradation or recruiting natural degradation mechanisms.

Molecular glues are a type of small-molecule degraders that primarily induce novel interactions between E3 ubiquitin ligases and target proteins, forming ternary complexes that lead to protein ubiquitination and subsequent proteasomal degradation. Compared with PROTACs, molecular glues generally have lower molecular weights, higher cell permeability, and better drug-like properties. Additionally, the design of molecular glues is relatively simple, without the requirements for complex linkers and ligand optimization. As a result, molecular glues have gradually emerged as a promising therapeutic approach for various diseases.

Multiple types of molecular glues have been reported previously. Analysis of co-crystal complex structures reveals that CRBN-related molecular glues are more versatile. Therefore, MCE researchers select active molecules related to these targets as probes for artificial intelligence (AI) screening.Subsequently, molecular docking technology was used to verify whether the screened molecules retained the key pharmacophore features. Ultimately, we obtained 317 molecular glue analogs, and these compounds serve as powerful tools for the research of molecular glues.

Molecular Glue Virtual Library is constructed using generative AI technology, integrating the structural features, activity data of known molecular glues, and interaction information of ternary complexes (target protein-E3-molecular glue). Endowed with structural novelty, drug-likeness, diversity and synthesizability, it is applicable to molecular glue-based AI drug screening and large-scale virtual screening.

MCE builds this library based on high-quality molecular building blocks by virtue of robust computing power, coupled with rigorous reaction rules and optimized compound generation strategies. To ensure library quality, molecules with high synthetic difficulty, poor drug-likeness, PAINS and other undesirable molecules are excluded first. Subsequently, scaffold-based compound analysis is performed to screen drug-like diverse molecules for synthesizability evaluation; those with excessively high synthetic difficulty are removed, ultimately forming a large-scale molecular glue virtual library with structural diversity, synthesizability and drug-likeness.

Compounds in the library can be synthesized in only 1-2 chemical reaction steps. With MCE’s experienced chemical synthesis team, custom synthesis of different scales from milligram to kilogram can be easily achieved to meet diverse customer needs.

The most prominent mechanism of action of kinase inhibitors is their competition with ATP by binding to the hinge region of the kinase protein. Once the kinase is blocked by an inhibitor, it loses the ability to transfer phosphate groups from ATP to other molecules, resulting in the loss of kinase activity.

The hinge-binding region of kinase inhibitors mimics the interaction pattern between the ATP nucleobase and the kinase. MCE extracted thousands of kinase inhibitors from the ChEMBL database and isolated their molecular fragments. In certain cases, the amino and amide groups on the molecular fragments are crucial for binding in the hinge region. Therefore, we enhanced the diversity of the collected results by adding these two groups to unoccupied positions on the ring system. Subsequently, the fragments were assessed for their hinge region binding ability via docking at distinct kinases, we also applied pharmacophore constraints to ensure interactions with key amino acids in the kinase hinge region, ultimately obtaining kinase-related molecular fragments.

MCE provides over 12,412 kinase fragment molecules that meet the above requirements and are available off the shelf, serving as an effective tool for screening and developing drugs targeting kinases.

CRBN, namely cereblon, is the substrate recognition subunit of the E3 ubiquitin ligase complex in the ubiquitin-proteasome system. A CRBN ligand library refers to a collection of numerous fragments that can specifically bind to the CRBN protein.

These ligands are mostly designed based on validated CRBN-binding warheads and modified through AI-driven molecular generation optimization systems. They not only include classic lenalidomide-derived structures but also cover novel non-lenalidomide scaffolds. After drug-likeness filtering, these ligands exhibit structural diversity and favorable druggable properties. They can be further optimized and modified to facilitate the development of novel molecular glue degraders, accelerate the discovery of molecular glues that induce interactions between CRBN and new substrate proteins, and enable the exploration of novel CRBN substrates for identifying previously unknown CRBN-binding proteins.

MCE compiles 125 fragments that can specifically bind to the CRBN protein, with molecular weights ranging from 200 to 500. Compounds developed based on the library ligands target multiple disease targets such as cancer and autoimmune diseases, further advancing the development of Molecular Glues and PROTACs therapeutic agents.

Metabolomics, positioned as the systemic characterization of small-molecule metabolites within biological systems, has emerged as an indispensable analytical platform in both fundamental research and translational applications across plant sciences, microbial biotechnology, and biomedical investigations. Functioning as a critical component in multi-omics integration, this discipline deciphers the intricate molecular networks operating downstream of genomic, transcriptomic, and proteomic regulation, thereby capturing the dynamic biochemical phenotype closest to organismal functionality. The metabolome, comprising endogenous compounds with molecular weights typically below 1500 Da, serves as the functional readout of cellular processes and environmental interactions, where perturbations in metabolic networks are frequently implicated in disease pathogenesis. Such unique attributes have propelled metabolomics into a pivotal role in pharmacological research, particularly in target deconvolution, pharmacodynamic assessment, and mechanistic elucidation of pathological processes.

MCE can provide 5,923 mass spectrometry human metabolites that can be used for metabolite identification and quantification, functional cell detection and phenotypic screening of mass spectrometry.

Unnatural amino acids (UAAs), also referred to as non-canonical amino acids (ncAAs) or non-proteinogenic amino acids, are a class of amino acids that are distinct from the 20 standard natural amino acids. They can be obtained through chemical synthesis, biosynthesis, and other approaches, with structural diversity far exceeding that of natural amino acids. UAAs are mainly including naturally occurring non-canonical amino acids, chemically synthesized amino acids, and biosynthetic amino acids, which provide a molecular basis for protein function design.

UAAs exhibit significant value in multiple fields. They can optimize the pharmacokinetic properties of peptide drugs and peptidomimetics, modify enzyme functions and endow them with new biological activities, thereby overcoming the limitations of traditional peptide drugs and expanding the chemical space . Meanwhile, UAAs can serve as molecular probes to analyze protein-protein interactions and investigate the regulatory mechanisms of protein functions.

MCE has compiled a UAAs Fragment Library comprising nearly a thousand unnatural amino acid fragments with extensive coverage of chemical space and enhanced structural diversity. This compound library can be widely applied in peptide synthesis, drug design, and protein engineering.

Cyclic peptide library have advantages such as high affinity, high selectivity, and suitability for targeting protein–protein interactions. Through DEL synthesis technology, the library size can achieve hundreds of millions. DEL cyclic peptide library have advantages like low cost andhigh screeing efficiency, making them valuable for discovering lead compounds against challenging drug targets.

This cyclic peptide library is constructed with unnatural amino acids as building block, synthesized through DNA-compatible chemical reactions. Each cyclic peptide consist of six amino acids and constrained conformations such as side-chain cross-linking, disulfide bonds, and macrocyclization. These cyclic peptides exhibit significantly improved stability and druggability compared with linear peptides, filling the gap between small molecules and macromolecular biologics. Each cyclic peptide is uniquely conjugated to a DNA barcode sequence for molecular identification and sequencing decoding.

MCE’s cyclic peptide library has8 independent sub-libraries, with a total molecular diversity of 1.2 billion. It is constructed via multi-round combinatorial assembly of building blocks and diverse cyclization strategies, facilitating the discovery of cyclic peptide leads for undruggable targets.

A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the formation of new protein products. Proteases play important roles in regulating multiple biological processes in all living organisms, such as regulating the fate, localization, and activity of many proteins, modulating protein-protein interactions, creating new bioactive molecules, contributing to the processing of cellular information, and generating, transducing, and amplifying molecular signals.

Proteases are important targets in drug discovery. Some protease inhibitors are often used as anti-virus drugs and anti-cancer drugs. MCE offers a unique collection of 927 protease inhibitors. MCE Protease Inhibitor Library is critical for drug discovery and development.

Peptidomimetics are compounds whose essential elements (pharmacophore) mimic a natural peptide or protein in 3D space and which retain the ability to interact with the biological target and produce the same biological effect. Peptidomimetics are designed to circumvent some of the problems associated with a natural peptide: e.g. stability against proteolysis (duration of activity) and poor bioavailability. Certain other properties, such as receptor selectivity or potency, often can be substantially improved. The design and synthesis of peptidomimetics are most important because of the dominant position peptide and protein-protein interactions play in molecular recognition and signaling, especially in living systems. Hence mimics have great potential in drug discovery.

MCE Peptidomimetic Library contains 370 compounds including peptoid, α-helix mimetics, β-turn/sheets mimetics, etc. This library is an indispensable tool of structure-activity relationships in drug discovery.

19F-NMR has proved to be a detection mode in fragment-based drug discovery (FBDD) for studies of protein structure and interactions. 19F shows high sensitivity for NMR detection, and the exquisite sensitivity of 19F chemical shifts and linewidths to ligand binding all make it a valuable approach in FBDD.F (Fluorine) -Fragments can be used for 19F-NMR detection after binding to target proteins, and can be used as an effective 19F-NMR tool for FBDD.

MCE designs a unique collection of 5,123 F-fragments, all of which obey a heuristic rule called the “Rule of Three (RO3)”, in which molecular weight ≤300 Da, the number of hydrogen bond donors (H-donors) ≤3, the number of hydrogen bond acceptors (H-acceptors) is ≤3 and cLogP is ≤3. This F-fragments library is an important source of lead-like drugs.

Cysteine proteases (CPs), a key enzyme family regulating physiological metabolism and mediating pathological processes (such as abnormal bone resorption, tumour invasion, and pathogen infection), represent a core therapeutic target for developing specific inhibitors in disease intervention. Currently reported CP inhibitors primarily achieve their inhibitory function by precisely binding to CP active pockets (e.g., S1-S4 non-primed regions or S1'-S2' primed regions) and forming covalent/non-covalent interactions with the active site cysteine residues, providing clear structural references for the development of novel inhibitors.

This compound library, designed based on the core strategy of "similarity-based known active structures", contains over 200 cysteine protease inhibitors. Leveraging AI-driven molecular screening technology, it retains the critical pharmacological and shape features of reported CP inhibitors, serving as a specialized tool for efficiently discovering novel cysteine protease inhibitors.

DEL technology enables the simultaneous screening of millions or billions of compounds in a single tube by covalently linking each small molecule with a unique DNA sequence. Traditional DEL screening primarily focuses on identifying non-covalent binding molecules, where interactions with the target are reversible. In contrast, DNA‑encoded covalent library is an ultra‑high‑throughput screening library developed on the basis of conventional DNA‑encoded library technology. It incorporates controllable electrophilic covalent warheads capable of forming irreversible covalent bonds with amino acid residues at the active sites of target proteins, including Cys, Lys, Ser, Tyr, and others. This covalent binding enhances binding affinity, prolongs residence time at the target site, and has the potential to overcome challenges associated with traditional non-covalent inhibitors, such as drug resistance or off-target effects.

Each compound in the library contains both a binding domain and an electrophilic warhead. It first recognizes and binds to the target through non covalent interactions, and then forms a stable covalent bond with key amino acid residues to achieve irreversible inhibition. This library is specifically designed for the discovery of potent, long lasting, and highly selective covalent inhibitors, particularly for undruggable targets such as kinases, GPCRs, proteases, and mutant oncoproteins. Each molecule is uniquely labeled with a DNA barcode for molecular identification and sequencing decoding.

This library is an advanced and highly diverse collection, consists of 35 independent sub-libraries with a total scaleof 14 million compounds, It incorporates over 14 experimentally validated covalent warheads capable of targeting cysteine, lysine, arginine, aspartic acid and glutamic acid. This library is constructed with diverse drug like core scaffolds and integrated controllable covalent warheads, it features structural diversity, reaction spec

Currently,the incidence and mortality rates of clinical fungal infections remain high. Existing antifungal drugs are limited in variety and associated with numerous adverse effects, creating an urgent demand for the development of novel antifungal agents. Antifungal compound libraries can support the screening and development of new antifungal drugs.

The mechanisms of action of antifungal drugs cover key processes such as fungal cell membrane synthesis, cell wall synthesis, and cell division. They exert fungicidal or fungistatic effects by specifically targeting different molecular pathways. This library includes a variety of core analogs of antifungal drugs, making it adaptable to antifungal research in diverse scenarios. It can be used for the high-throughput screening of novel antifungal drug candidates, enabling the rapid identification of compounds with potential antifungal activity and facilitating the elucidation of drug-target interactions and resistance mechanisms. Additionally, it supports the screening of compounds and combinations that reverse drug resistance, thereby uncovering the novel antifungal potential of existing compounds.

The library comprises 8350 compounds with a well-defined screening strategy. The core sources of the compounds include analogs of known antifungal active moleculeswith a similarity score of ≥ 0.6 MCE has collected more than 500 antifungal molecules.All screened compounds conform to lead-like physicochemical properties, exhibiting both structural diversity and drug-like characteristics, and providing valuable support for the research and development of novel antifungal drugs.