containing

Aging is a complex biological process characterized by functional decline of tissues and organs, structural degeneration, and reduced adaptability and resistance, all of which contribute to an increase in morbidity and mortality caused by multiple chronic diseases, such as Alzheimer's disease, cancer, and diabetes. Many theories, which fall into two main categories: programmed and error theories, have been proposed to explain the process of aging, but neither of them appears to be fully satisfactory. The programmed theories imply that aging relies on specific gene regulation, and the error theories emphasize the internal and environmental damages accumulated to living organisms. The damage theories proposed the nine hallmarks that were generally considered to contribute to the aging process: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication.

MCE Anti-Aging Compound Library contains 7,771 compounds, mainly targeting Sirtuin, mTOR, IGF-1R, AMPK, p53, Telomerase, Mitophagy, Mitochondrial Metabolism, COX, Cytochrome P450, Oxidase, etc. This library is a useful tool for anti-aging research.

Tonifying traditional Chinese medicines occupy a central position in the traditional medical system, with their core value lying in the regulation of the body's functional state. Modern pharmacological studies have confirmed that these medicinal materials and their monomeric components possess multiple biological activities, including bidirectional immune regulation, anti-aging and lifespan extension, neuroprotection and cognitive enhancement, as well as hematopoietic and metabolic regulation. According to the traditional Chinese medicine theory of “strengthening the body’s resistance and consolidating the foundation”, tonifying medicines are mainly classified into four major categories: Qi-tonifying, Blood-tonifying, Yin-tonifying, and Yang-tonifying. This compound library strictly follows this classification system for compound collection.

Monomeric compounds derived from traditional Chinese medicines demonstrate excellent drug-like properties. They naturally possess structural diversity and clearly defined pharmacological activities, which help improve screening success rates and make them ideal tools for studying multi-target synergistic effects. This library contains 1,039 compounds, providing a material basis for investigating synergistic interactions among compounds (network pharmacology) and facilitating the development of multi-target therapeutic strategies for complex diseases such as cancer, neurodegenerative disorders, and metabolic syndrome.

Liposomes are spherical or multilayered spherical vesicles formed by the self-assembly of diacyl chain phospholipids (lipid bilayers) in aqueous solutions, which can be made from natural or synthetic phospholipids and exhibit good biocompatibility and low toxicity. They can serve as delivery carriers for various bioactive substances (such as drugs, proteins, nucleic acids, etc.) and are widely used in biomedical and chemical research. The main advantages of liposomes include 1) Protective effect: Their bilayer structure can protect encapsulated molecules from enzymatic degradation, oxidation, and other influences, extending stability and activity; 2) Active targeting: Surface modifications enable active targeting, enhancing the concentration of drugs or molecules in specific tissues or cells; 3) Customizability: The composition and structure of liposomes can be adjusted according to needs, such as altering phospholipid types or adding targeting ligands. These properties make liposomes highly valuable in developing novel drug delivery systems, serving as nucleic acid carriers for gene transfection, studying cellular uptake mechanisms and drug release kinetics, as well as developing functional food additives to improve the bioavailability of nutritional components.

MCE contains 227 liposome compounds, which is a good tool for drug delivery-related studies.

Lactic acid metabolism is one of the key metabolic pathways within living organisms. It plays a crucial role not only in cellular energy conversion but is also closely related to a variety of physiological and pathological processes. The production and clearance of lactic acid are important indicators of cellular metabolic balance, and its abnormal regulation may lead to conditions such as lactic acidosis, muscle fatigue, and hereditary metabolic diseases. Moreover, lactic acid is closely related to the malignancy of tumors and is considered a biomarker for malignant tumors and poor prognosis. Lactic acid can serve as a metabolic substrate to support the metabolic needs of tumor cells under hypoxic conditions, and it can also cause acidification of the tumor microenvironment, suppress immune cell function to promote immune evasion, and induce drug resistance in tumor cells. Currently, targeting lactic acid-lactylation and its related metabolic pathways has become a new research avenue for cancer treatment. In-depth exploration of the molecular mechanisms of lactic acid metabolism can help in screening lead compounds that regulate the lactic acid metabolism.

MCE contains 582 small molecule compounds targeting enzymes involved in lactic acid metabolism. This library is of significant value for researching the role of lactate metabolism in the mechanisms of diseases.

Techniques for reprogramming somatic cells create new opportunities for drug screening, disease modeling, artificial organ development, and cell therapy. The development of reprogramming techniques has grown exponentially since Yamanaka reprogrammed somatic cells to become induced pluripotent stem cells (iPSCs) using four transcription factors, OCT4, SOX2, KLF4, and c-MYC in 2006. Despite the development of efficient reprogramming methods, most methods are inappropriate for clinical applications because they carry the risk of integrating exogenous genetic factors or use oncogenes. Alternative approaches, such as those based on miRNA, non-viral genes, non-integrative vectors, and small molecules, have been studied as possible solutions to the problems. Among these alternatives, small molecules are attractive options for clinical applications. Reprogramming using small molecules is inexpensive and easy to control in a concentration- and time-dependent manner. It offers a high level of cell permeability, ease of synthesis and standardization, and it is appropriate for mass-producing cells.

MCE Reprogramming Compound Library contains a unique collection of 3,231 compounds that act on reprogramming signaling pathways. These compounds are potential stimulators for reprogramming. This library is a useful tool for researching reprogramming and regenerative medicine.

Ionizable lipids are a class of specialized, functional lipid molecules with pH-sensitive charge characteristics. They are primarily divided into two major categories: ionizable cationic lipids and ionizable anionic lipids, though the term typically specifies ionizable cationic lipids within the biomedical field. Structurally, these lipids consist of an ionizable hydrophilic headgroup, a biodegradable linker, and hydrophobic tails. Their primary application is serving as the key delivery vehicle in lipid nanoparticles (LNPs) to encapsulate negatively charged nucleic acid macromolecules, such as mRNA vaccines, siRNA therapeutics, and CRISPR gene-editing components. In a physiological, neutral environment, they remain electrically neutral to minimize systemic toxicity and prolong circulation time. Upon entering the acidic microenvironment of cellular endosomes, however, they undergo protonation to become positively charged, thereby inducing membrane fusion and enabling the highly efficient intracellular release of the nucleic acid cargo. Consequently, they serve as the technological cornerstone for bringing nucleic acid therapies into clinical application.

To accelerate the translational process of cutting-edge nucleic acid drugs, MCE has meticulously constructed an ionizable lipid compound library containing 93 high-performance molecules, aiming to provide researchers and pharmaceutical professionals with a high-throughput, multi-dimensional lipid screening platform.

PD-1/PD-L1 are key immune checkpoint targets that suppress T-cell-mediated anti-tumor immunity, representing a major focus in cancer immunotherapy. While antibody drugs dominate the clinic, they are limited by administration challenges and immune-related side effects. Small-molecule PD-1/PD-L1 inhibitors, with oral availability, good tissue penetration and low cost, have emerged as a promising next-generation strategy.

A PD-1/PD-L1 lead-like library was built via a five-step virtual screening process. After collecting 8,947 inhibitors from BindingDB and PubChem and filtering by activity and duplicates, AI similarity screening was performed using GeminiMol. Key pharmacophores were extracted from the PPI interface of co-crystal structures, and molecular was screened via a pharmacophore model, effectively enhancing target activity.

Containing 10,000 structurally diverse and drug-like molecules well-matched to the PD-L1 pocket, the library supports virtual docking, high-throughput screening and hit discovery, enabling efficient and rapid development of small-molecule immunotherapies.

In the progression of various diseases, metabolic reprogramming has emerged as a key hallmark. Lactate, as an important metabolic signaling molecule, is widely involved in tumorigenesis, immune regulation, and inflammatory responses. Particularly within the tumor microenvironment, the abnormal accumulation of lactate not only affects cellular energy metabolism but also promotes disease progression by modulating immune cell functions and mediating protein lactylation, thereby participating in epigenetic regulation and signaling networks. Therefore, systematic investigation of lactate metabolic pathways and their associated metabolites is of great significance for understanding disease mechanisms and developing novel therapeutic strategies.

The MCE lactic acid metabolite compound library contains 61 compounds and is constructed around key metabolic pathways involving lactate production, transport, and utilization. This library systematically includes core intermediates from glycolysis, the tricarboxylic acid (TCA) cycle, and the lactate cycle. Focusing on disease-associated metabolic reprogramming, it is suitable for research in oncology, inflammation, and metabolic disorders. The library can be used to elucidate the roles of lactate in tumor microenvironment regulation, immune evasion, and epigenetic modifications (such as protein lactylation). In addition, it provides high-quality small-molecule resources for drug screening, facilitating the discovery of potential modulators targeting key enzymes (such as LDH) or transporters (such as MCTs) involved in lactate metabolism.

Drug-induced liver injury (DILI; also known as drug-induced hepatotoxicity) is caused by medications (prescription or OTC), herbal and dietary supplements (HDS), or other xenobiotics that result in abnormalities in liver tests or in hepatic dysfunction that cannot be explained by other causes. Drugs are an important cause of liver injury. Drug-induced hepatic injury is the most common reason cited for withdrawal of an approved drug.

DILI is thought to occur via several different mechanisms. Among these are direct impairment of the structural (e.g., mitochondrial dysfunction) and functional integrity of the liver; production of a metabolite that alters hepatocellular structure and function; production of a reactive drug metabolite that binds to hepatic proteins to produce new antigenic drug-protein adducts, which are targeted by hosts’ defenses (the hapten hypothesis); and initiation of a systemic hypersensitivity response (i.e., drug allergy) that damages the liver.

MCE Drug-induced Liver Injury (DILI) Compound Library contains a unique collection of 641 hepatotoxicity causing compounds and is a powerful tool to research DILI and other drug toxicities. This library can be used to understand the mechanisms of DILI, identify biomarkers for early DILI prediction, and allow timely recognition during drug development, thus finally achieving successful DILI prevention and assessment in the pre-marketing phase.

Small molecule covalent inhibitors, or irreversible inhibitors, are a type of inhibitors that exert their biological functions by irreversibly binding to target through covalent bonds. Compared with non-covalent inhibitors, covalent inhibitors have obvious advantages in bioactivity, such that covalent warheads can target rare residues of a particular target protein, thus leading to the development of highly selective inhibitors and achieving a more complete and continued target occupancy in living systems. In recent years, the distinct strengths of covalent inhibitors in overcoming drug resistance had been recognized. However, toxicity can be a real challenge related to this class of therapeutics due to their potential for off-target reactivity and has led to these drugs being disfavored as a drug class. The drug design and optimization of covalent inhibitors has become a hot spot in drug discovery.

MCE covalent inhibitor library contains 6,121 small molecules including identified covalent inhibitors and other molecules having common covalent reactive groups as warheads, such as acrylamides, activated terminal acetylenes, sulfonyl fluorides/esters, cloracetamides, alkyl halides, epoxides, aziridines, disulfides, etc.

MCE Covalent inhibitor Library plus, with more powerful screening capability, further complement Covalent inhibitor Library (HY-L036) by adding some fragment compounds with covalent warheads.

The RNA-targeted bioactive compound library is a high-quality collection of small molecules specifically designed and curated to target RNA structures and functions. It is widely applied in cutting-edge drug discovery and life science research. Unlike traditional strategies that focus on protein targets, RNA-targeted compounds can directly modulate various functional RNA molecules by influencing their splicing, translation, stability, or structural conformation, thereby enabling precise intervention in key biological processes. In the field of drug development, these compounds provide a novel approach to addressing previously “undruggable” targets and have demonstrated significant potential in areas such as oncology, antiviral therapies, and neurodegenerative diseases. For example, by targeting disease-associated RNA structural domains or regulating the aberrant expression of non-coding RNAs, these compounds can effectively inhibit disease progression or restore normal cellular function. In mechanistic studies, RNA-targeted compounds serve as valuable chemical biology tools to elucidate the roles of RNA in gene expression regulation, cellular signaling pathways, and disease development.

The MCE RNA-targeted bioactive compound library contains 858 compounds, sourced from databases such as TargetRX Atlas and R-BIND. The library features excellent structural diversity and biological activity, making it suitable for high-throughput screening (HTS), target validation, phenotypic screening, and lead compound discovery. It represents a valuable resource for RNA-related research and innovative drug development.

Stem cells, which are found in all multi-cellular organisms, can divide and differentiate into diverse special cell types and can self-renew to produce more stem cells. To be useful in therapy, stem cells must be converted into desired cell types as necessary which is called induced differentiation or directed differentiation. Understanding and using signaling pathways for differentiation is an important method in successful regenerative medicine. Small molecules or growth factors induce the conversion of stem cells into appropriate progenitor cells, which will later give rise to the desired cell type. There is a variety of signal molecules and molecular families that may affect the establishment of germ layers in vivo, such as fibroblast growth factors (FGFs); the wnt family or superfamily of transforming growth factors β (TGFβ) and bone morphogenetic proteins (BMP). Unfortunately, for now, a high cost of recombinant factors is likely to limit their use on a larger scale in medicine. The more promising technique focuses on the use of small molecules. These small molecules can be used for either activating or deactivating specific signaling pathways. They enhance reprogramming efficiency by creating cells that are compatible with the desired type of tissue. It is a cheaper and non-immunogenic method.

MCE Differentiation Inducing Compound Library contains a unique collection of 2,574 compounds that act on signaling pathways for differentiation. These compounds are potential stimulators for induced differentiation. This library is a useful tool for researching directed differentiation and regenerative medicine.

RNA is crucial for the regulation of numerous cellular processes and functions. With the in-depth study of disease mechanisms, processes such as RNA expression, splicing, translation, and stability regulation have become new targets for disease intervention. RNA has provided new therapeutic modalities for metabolic diseases, genetic disorders, and cancer patients, resulting in several innovative drugs.

MCE R&D team collected small molecules targeting RNA from the PDB, R-BIND, ROBIN, and internal database as the positive dataset, and non-targeting RNA small molecules from ROBIN as the negative dataset. Based on the GeminiMol pre-trained model, we encoded the molecules and calculated over 1700 molecular descriptors using Mordred as inputs for the model. Subsequently, we employed 13 deep learning models to learn from the data. All of which yielded good training results, with AUROCs greater than 0.75. Ultimately, we selected the Finetune model to screen HY-L901P, which exhibited the best classification performance, achieving an AUROC of 0.82 and a prediction accuracy of 0.76. We then applied filtering based on StaR rules (with at least two of the following properties: cLogP ≥ 1.5, Molar Refractivity ≥ 4, Relative Polar Surface Area ≤ 0.3) to obtain a library containing approximately 5,000 small molecule compounds targeting RNA. This library serves as a valuable tool for screening small molecules that interact with RNA.

Spirocyclic compounds, with rigid 3D structures, high Fsp³ and strong conformational restriction, are highly privileged scaffolds in small-molecule drug screening. They overcome drawbacks of planar aromatic compounds such as poor solubility, high off-target risks and weak druggability. Their orthogonal bicyclic geometry fits well into protein pockets, improving target affinity, subtype selectivity, metabolic stability and membrane permeability, making them ideal for hit identification against kinases, GPCRs, PPIs and other targets.

Spirocyclic scaffolds have been widely applied in oncology, antivirals, hypertension and CNS diseases, leading to many approved drugs and clinical candidates. SAR studies show that spiro-atom chirality, ring size and heteroatom substitution dominate bioactivity and selectivity, with the scaffold mainly serving as a conformational anchor. Azaspirocycles, spirooxindoles and spirosteranes target GPCRs, kinases, MDM2-p53 and PPIs. Approved drugs including irbesartan, spironolactone and rolapitant confirm their druggability, while revumenib and SAR405838 show promise against undruggable targets.

The MCE Spirocyclic Druglike Library contains over 1,000 diverse, stereospecific molecules selected by Lipinski’s rules. It covers privileged cores such as azaspirocycles, oxaspirocycles and spirooxindoles. These molecules bear rich chiral centers and distinct 3D orientations, reducing non-specific binding and enhancing screening efficiency. Featuring novel scaffolds, the library offers a highly innovative starting point for drug discovery.

Carbohydrate metabolism serves as a central hub for energy supply and biosynthesis in living organisms and plays a critical role in the onset and progression of various diseases. In recent years, studies have shown that tumor cells reprogram their energy metabolism through aerobic glycolysis (the Warburg effect) to support rapid proliferation. Immune cells also rely on specific carbohydrate metabolic pathways to regulate their activation and differentiation states, while disorders such as diabetes and metabolic syndrome arise directly from dysregulation of carbohydrate metabolism. In addition, enzymes and key metabolic nodes involved in carbohydrate metabolism have become important targets for drug discovery, and therapeutic strategies targeting glycolysis, the pentose phosphate pathway, and energy metabolism are continuously advancing the treatment of cancer and metabolic diseases. Therefore, systematic analysis of carbohydrate metabolic networks and their associated metabolites is of great significance for elucidating disease mechanisms and developing novel therapeutic approaches.

The MCE Carbohydrate Metabolism Metabolite Library is constructed based on classical carbohydrate metabolic pathways and contains 76 metabolites. It systematically integrates key metabolic networks, including glycolysis, the pentose phosphate pathway, the tricarboxylic acid (TCA) cycle, monosaccharide metabolism, and sugar acid interconversions. The library comprehensively covers core metabolic nodes from glucose uptake and utilization to energy production and biosynthesis, while also incorporating important upstream and downstream intermediates. It enables accurate representation of intracellular metabolic flux dynamics and is well suited for applications such as metabolic flux analysis, target validation, and mechanistic studies. Furthermore, it provides robust support for multi-omics integration and the development of precision intervention strategies.

The rising prevalence of multidrug-resistant and extensively drug-resistant bacteria, combined with emerging resistance mechanisms and the limitations of existing antibacterial drugs, creates an urgent need for novel antibacterial agents. Antibacterial compound libraries serve as key tools to support antibacterial drug screening and development.

This library features structurally diverse compounds, including small-molecule scaffolds and natural product derivatives, and exhibits diverse antibacterial mechanisms of action. For example, these compounds exert antibacterial effects by disrupting bacterial cell structures, interfering with bacterial metabolic processes, and inhibiting nucleic acid synthesis. The derivation of scaffold structures enhances their activity against drug-resistant bacteria and their selectivity against different types of bacteria. This library can be used for the high-throughput screening of novel antibacterial drug candidates and the identification of potent compounds against drug-resistant and multidrug-resistant bacteria. Additionally, it provides a reference for compound structural modification, enabling further in-depth research on the structure-activity relationships(SARs) of antibacterial drugs. It can also be applied to the exploration of bacterial resistance mechanisms and reversal strategies, as well as the discovery of antibacterial molecules that inhibit efflux pumps and restore drug susceptibility.

The library contains 10855 structurally diverse drug-like compounds. Its core compound sources include analogs of known antifungal active moleculeswith a similarity score of ≥ 0.6. MCE has collected more than 1900 antibacterial molecules. All screened compounds conform to lead-like physicochemical properties, providing valuable support for the research and development of novel antibacterial drugs.

The discovery of hit molecule is a cornerstone of drug development. Among the diverse tools available, DNA-encoded libraries have emerged a revolutionary platform for high-throughput screening. Compared with traditional HTS, DEL features shorter screening processes, lower costs, simpler assays, and larger library capacities.

DEL Construction utilizes split-and-pool synthesis, a combinatorial chemistry approach that involves iterative splitting, reaction, and pooling. This strategy enables rapid, exponential assembly of fragments in minimal steps without the need for individual compound synthesis andassoicicated isolation or purification steps, thus greatly reducing overall costs. The technology enables simultaneous affinity screeningof massive compound collections to target proteins in a single step. By coupling chemical structures with unique DNA barcodes, each compound is tagged with a distinct DNA sequence for convenient tracking and decoding.DELs readily enable the construction and efficient screening of libraries containing millions to billions of compounds. As a result, DEL screening combines the dual advantages of high efficiency and low cost, making DEL a transformative technology in modern drug discovery.

The DEL kit consists of 50 independent libraries with a total scale of 100 billion compounds. It is constructed through stepwise combinatorial chemistry strategies involving 2-, 3-, and 4-round synthesis. By employing diverse scaffolds and flexible linking strategies, it encompasses various ring systems, linear frameworks, and heterocyclic structures. Screening can be achieved solely through affinity, independent of target-specific activity detection methods. This library is suitable for DEL screening against a wide range of targets.

Recently, significant advancements in tyrosine-targeting electrophiles have primarily occurred in the field of protein-protein interactions (PPIs), where cysteine residues are often underrepresented and novel chemistries are needed to address these interfaces. In this context, tyrosines are frequently more accessible compared to more buried binding sites. Moreover, they are commonly found at "hot spots," which are functional epitopes of PPIs, with 12.3% of the residues consisting of tyrosines. This prevalence is likely due to the hydrophobic nature of tyrosine, its ability to participate in aromatic π-interactions, and its capacity for hydrogen bonding. Beyond PPIs, some progress has also been made in covalent tyrosine targeting in other areas where more commonly addressed side chains are lacking. Even though tyrosine has a slightly lower pKa value compared to the protonated lysine side chain (approximately 10 vs. 10.5 for the unprotected amino acid side chains), significantly less progress has been made in the development of tyrosine-targeted covalent ligands compared to lysine. This is likely due to the reduced flexibility of the tyrosine side chain and the greater steric hindrance of its hydroxy group, which makes it more challenging to adopt suitable reaction geometries.

Through careful selection, we constructed a structural filter containing over 110 electrophilic groups. By analyzing the electrophilic fragments selected by the structural filter, we removed any molecules with trivial or undesirable structural features. Ultimately, we obtained 124 fragment molecules which can target tyrosine residue and can be used for fragment-based covalent drug discovery.

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