multiple

“BioDesign” approach incorporates key structural features of known pharmacologically relevant natural products (e.g. alkaloids and other secondary metabolites) into synthetically feasible medicinal chemistry scaffolds. In order to identify the privileged pharmacophores, ring systems and linkers, we have carried out statistical analysis of structural features of natural products, marketed drugs, and drug candidates.

Saturated, fused ring, spiro, and bridged systems with a tendency towards multiple chiral centers are highly privileged among natural products and marketed drugs yet these structures are very poorly represented in commercial libraries. This library addressed this market need by incorporating these privileged elements into the design of novel synthetic molecules with high molecular framework diversity, multiple stereogenic centers (≥2), and degree of saturation (Fsp3 > 0.5).

MCE 5K Scaffold Library consists of 5,000 lead-like compounds. Each compound represents one unique scaffold. All compounds are compatible with Lipinski’s rule (Rule of 5) with multiple characteristics such as calculated good solubility (-3.2 < logP < 5), oral bioavailability (RotB <= 10), drug transportability (PSA < 120). Compounds contained within the library have been screened to remove any inappropriate chemical structures, avoiding “false hits”. The sufficient diverse of compound structure makes this library a powerful tool for drug screening.

Agonistic drugs activate or stimulate their receptors, triggering responses that increase or decrease cell activity. The highly selective activators can act on specific biological or molecular targets, while non-selective activators may interfere with multiple targets or targets simultaneously. The highly selective activators reduce the likelihood of these non-specific effects by targeting specific targets, making research more precise and reliable. The Highly Selective Activators Library contains 2,056 compounds, covering multiple targets and subtypes, such as GPCR protein family, Ion channel, multiple kinases, etc. The Highly Selective Activators Library is an effective tool for screening different phenotypes.

The occurrence of diseases is often associated with multiple targets and pathways, and the factors of disease formation are complex and diverse, so the development of more powerful drugs is needed. According to statistics, 21% of the FDA-approved drugs in 2015-2017 were multi-target compounds. Multi-target compounds refer to a drug targeting multiple disease-related targets or multiple subtypes of a target. Multi-target compounds can be applied to drug screening or targeted ligand design. Because the targets of such compounds are diverse and clear, they have the characteristics of saving time and drug cost during the mechanism research of new drug research and development. In addition, due to the diversity of drug targets, multiple strategies can be applied to pharmacological studies.

MCE supplies a unique collection of 6,666 multi-target compounds that targets two or more different targets or different subtypes of the same target. MCE Multi-Target Compound Library can be used for target protein ligand screening or drug development.

Traditional Chinese medicine provides abundant natural resources for medicinal compounds, which are often considered effective and safe for drug discovery. Traditional Chinese medicine is based on the principle of "multiple components, multiple targets, and multiple pathways", and naturally has multiple pharmacological effects. As herbal medicine, the secondary plant metabolites in Chinese herbal medicine play an important role in alleviating many diseases in Traditional medicine and folk use. Therefore, the identification of traditional Chinese medicine derived compounds is also an important process in drug development and a necessary factor in dissecting the overall mechanism of action of traditional Chinese medicine. FDA listed compounds have completed extensive preclinical and clinical studies, exhibiting good biological activity, safety, and bioavailability.

MCE designs a unique collection of 306 FDA/EMA/NMPA/PMDA etc-approved traditional Chinese medicine active compounds, including flavonoids, polyphenols, alkaloids, terpenoids, and other structural types. It is a good tool for drug reuse and screening drugs from traditional Chinese medicine sources.

MCE 50K Diversity Library consists of 50,000 lead-like compounds with multiple characteristics such as calculated good solubility (-3.2 < logP < 5), oral bioavailability (RotB <= 10), drug transportability (PSA < 120). These compounds were selected by dissimilarity search with an average Tanimoto Coefficient of 0.52. There are 36,857 unique scaffolds and each scaffold 1 to 7 compounds. What’s more, compounds with the same scaffold have as many functional groups as possible, which make abundant chemical spaces. This exceptionally diverse library is highly recommended for random screening against new as well as popular targets based its novel, diverse scaffolds, abundant chemical spaces and the convenience for subsequent modification.

Phenolic compounds are usually referred to as a diverse group of naturally occurring compounds with multiple medical properties, such as antioxidants, antimicrobial properties. Those compounds are commonly found in food and plants. They have high synthetic, medicinal and industrial values. Polyphenols are compounds with multiple phenolic functionalities. Naturally occurring polyphenols are known to have biological activities for use as drugs, for example, in diseases like AIDS, heart ailments, ulcer formation, bacterial infection, mutagenesis and neural disorders.

MCE offers a unique collection of 1,281 natural phenol compounds which is a useful tool for drug discovery as an important source of lead compounds.

A unique set of molecules containing mild electrophilic moieties that covalently interact with amino acid residues in the target protein. The diversity of our compounds for covalent drug discovery ranges from natural product-like scaffolds to macrocycles, creating multiple opportunities in hit generation for a selected target.

According to reports, most known kinase inhibitors exert their effects through competitive binding in highly conserved ATP pockets. Although genetic techniques such as RNA interference can inactivate specific genes, most kinases are multi domain proteins, each of which has an independent function. Highly selective inhibitors have higher efficiency than non-selective inhibitors, and the selectivity to the target is at least 100 times higher. Therefore, ensuring the validation of targets with the most selective inhibitors is crucial for a more thorough understanding of the pharmacology of the kinase field. The Highly Selective Inhibitors Library contains 6,080 compounds, covering multiple targets and subtypes, such as GPCR protein family, Ion channel, multiple kinases, etc. The Highly Selective Inhibitors Library is an effective tool for screening different phenotypes

Adult stem cells are important for tissue homeostasis and regeneration due to their ability to self-renew and generate multiple types of differentiated daughters. Self-renewal is reflected by their capacity to undergo multiple/limitless divisions. Several signaling pathways are involved in self-renewal of stem cells, that is, Notch, Wnt, and Hedgehog pathways or Polycomb family proteins. Recent studies mainly focus on cancer stem cell (CSCs), induced pluripotent stem cell (iPSCs), neural stem cell and maintenance of embryonic stem cell pluripotency. Among them, CSCs have been believed to be responsible for tumor initiation, growth, and recurrence that have implications for cancer therapy.

MCE owns a unique collection of 2,685 compounds that can be used for stem cell regulatory and signaling pathway research.

Cancer is the second leading cause of death worldwide and a serious threat to human health. Multiple treatments have been developed for cancer treatment, but new anti-cancer drugs still need to be developed urgently. Approved drugs, have well-characterized bioactivities, safety and bioavailability properties, will dramatically accelerate drug development.

MCE offers a unique collection of 1,518 approved drugs with anti-cancer activity, which can be used for discovery of new anti-cancer drugs or as positive compounds used for anti-cancer research.

Peptides are a group of biologically active substances that are involved in various cellular functions of organisms. Peptides are often used in functional analysis, vaccine research and especially in the field of drug research and development. At present, more than 80 peptide drugs have reached the market for a wide range of diseases, including diabetes, cancer, osteoporosis, multiple sclerosis, HIV infection and chronic pain.

MedChemExpress (MCE) offers a comprehensive collection of 2,495 peptides, including bioactive peptides, amino acid derivatives, and blocking peptides. MCE Peptide Library can be used for peptide library screening, peptide drug discovery, vaccine development, target verification, structural activity research, etc.

Cysteine proteases (CPs), a key enzyme family regulating physiological metabolism and mediating pathological processes (e.g., abnormal bone resorption, tumour invasion, and pathogen infection), represent a core therapeutic target for disease intervention via the development of specific inhibitors. Currently reported CP covalent inhibitors encompass diverse structural types, including epoxides, aziridine, and activated double bonds (vinyl sulphones, α,β-unsaturated ketones), providing clear structural references for the development of novel CP covalent inhibitors.

This compound library contains multiple warheads that specifically target cysteine proteases, serving as a powerful tool for the efficient discovery of novel covalent inhibitors against this enzyme family.

Drug development is both expensive and time-consuming, with approximately one-third of drug discontinuations caused by severe adverse drug reactions (ADRs). Among these, drug-induced cardiotoxicity (DICT) is one of the primary reasons for late-stage clinical drug failures and market withdrawals. To date, cardiotoxicity has been observed in multiple drug classes, such as anticancer drugs, antipsychotics, antidepressants, antibiotics, and neurodegenerative disease medications. To reduce cardiac ADRs, it is crucial to determine the clinical relevance of DICT to treatment, elucidate the underlying molecular mechanisms, identify reliable biomarkers, and develop new diagnostic and therapeutic approaches.

MCE offers 257 cardiotoxicity compounds, including some FDA-approved drugs as well as inhibitors/blockers of the hERG potassium channel.

Polysaccharides are long chains of carbohydrate molecules, consisting of multiple smaller monosaccharides. Polysaccharides are found mainly in natural sources such as plants, microorganisms, algae and animals. Polysaccharides have a large number of active functional groups, different chemical compositions and different molecular weight ranges, which determines their diversity in nature and structure. Also in the field of medical research, polysaccharides act as a class of functional compounds and thus play a role. For example, nanocarrier construction, immunomodulation and vaccine development, new strategies for antitumor therapy, tissue regeneration engineering applications and disease diagnosis. With the advancement of glycomics and synthetic biotechnology, human beings are moving from “knowing polysaccharides” to “designing polysaccharides”, which will provide innovative solutions for materials science, precision medicine and sustainable development.

MCE offers 67 polysaccharides that can be used in biomedical studies.

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 914 protease inhibitors. MCE Protease Inhibitor Library is critical for drug discovery and development.

Rheumatoid Arthritis (RA) is a autoimmune disease characterized by persistent joint inflammation. The pathology of RA includes immune cell infiltration, synovial lining proliferation, pannus formation, and the destruction of joint cartilage and bone, which is highly disabling. Due to long-term chronic inflammation, RA not only severely affects the quality of life of patients but can also damage multiple organs, leading to lung diseases, cardiovascular diseases, and malignant tumors. The pathogenesis of RA is complex, involving genetic, environmental, and immune factors. With the advancement of high-throughput screening technology, screening for compounds targeting JAK, CCR, MEK, MMP targets may contribute to the development of more effective drugs against Rheumatoid Arthritis (RA).

MCE has collected 1,855 small molecule compounds with definite or potential anti-rheumatoid arthritis activity. This library is of significant value for researching the anti-RA drugs.

Cyclic peptides are polypeptide chains taking cyclic ring structure, which exhibit diverse biological activities, such as antibacterial activity, immunosuppressive activity and anti-tumor activity. Cyclic peptides, with the features of good binding affinity, target selectivity and low toxicity, show great success as therapeutics. Multiple cyclic peptides are currently in clinical use, for examples, gramicidin and tyrocidine with bactericidal activity, cyclosporin A with immunosuppressive activity, and vancomycin with antibacterial activity. Furthermore, cyclic peptides usually have the sufficient size and a balanced conformational flexibility/rigidity for binding to flat protein-protein interaction (PPI) interfaces, which have potential to develop PPI drugs.

MCE offers a unique collection of 96 cyclic peptides, all of which have good bioactivities. MCE Cyclic Peptide Library is a powerful tool for drug discovery and PPI inhibitor screening.

Human metabolism is an integral part of cellular function that reflects individual differences in health, disease, diet, and lifestyle. Many health conditions such as obesity, diabetes, hypertension, heart disease, and cancer are associated with abnormal metabolic states. In the pathological state of the human body, metabolic pathways are significantly altered, resulting in aberrant levels of intermediates or end-products that can be viewed as potential diagnostic biomarkers or even therapeutic targets. Therefore, detection, identification and quantification of human metabolites are very important for drug metabolism research in drug development.

MCE offers a unique collection of 6,664 human metabolites, including endogenous metabolites and exogenous metabolites, covering multiple structure types, such as lipids, amino acids, nucleic acids, carbohydrates, organic acids, biogenic amines, vitamins,. MCE Human Metabolites Library is a helpful tool for studying the relationship between diseases and metabolism.

The MCE 1K Drug Fragment Library consists of 1,366 drug fragments. These drug fragments are derived from 2,946 FDA-approved drug molecules, and fragments from one drug can appear in other drugs, so these fragments are somewhat correlated with good PK/PD properties. Fragment-based screening can reserve enough chemical space for subsequent structural optimization. This compound library is an essential tool for drug screening based on FBDD (Fragment-Based Drug Discovery).

Cell proliferation, the increase in cell numbers resulting from cell division, is a complex and tightly regulated process. Cell proliferation is regulated by coordinated entry into the cell cycle, and changes in proliferation are closely linked to disease development. Evolutionary dynamics links tumor growth and progression with cell proliferation, cell death, and mutation rates. In addition, cell proliferation is central to degenerative diseases, the development of which is often accompanied by accelerated multiplication of cancer cells. Therefore, assays of cell proliferation levels are frequently used for laboratory research purposes and increasingly for clinical assessment of tumor aggressiveness and potentially to guide care. It has been shown that multiple key targets are collectively involved in regulating the process of cell proliferation, such as CDK, E2F, pRB, β-Catenin, and others.

MCE collects 3,367 compounds that target and regulate key targets of cell proliferation, which can be used in studies of cell proliferation mechanisms and drug discovery.

Cell death plays a crucial role in the development of the body and the maintenance of internal balance to prevent the development of diseases. According to the regulation of the involved processes, cell death can be defined as programmed and non-programmed death. Programmed cell death (PCD) can be divided into lytic cell death and nonlytic cell death, mainly including apoptosis, necrotic apoptosis and Pyroptosis. Non-Programmed cell death (Non-PCD) generally refers to necrosis. In stark contrast to Accidental Cell Death (ACD), Regulatory Cell Death (RCD) relies on specialized molecular mechanisms. Cell death includes internal apoptosis, external apoptosis, necrotic apoptosis, ferroptosis, pyroptosis, lysosome-dependent cell death, etc.

MCE designs a unique collection of 3,603 cell death compounds, covering multiple targets, such as Apoptosis, Ferroptosis, Pyroptosis, Necroptosis, etc. It is a useful tool for screening cell death drugs.

Autoimmune disease is a pathological disease characterized by inflammatory disorders targeting autoantigens. The routine treatment of autoimmune diseases suppresses general immune function to regulate uncontrolled inflammation. The current targeted immunotherapy suppresses the main pro-inflammatory signaling pathways by blocking inflammatory cytokines, cell surface molecules, and intracellular kinases. As key participants in innate immunity, macrophages and dendritic cells (DCs) are crucial for Ag presentation and pro-inflammatory cytokine production, such as TNF and IL-1 β、 IL-6, IL-23, B cell activating factor (BAFF), and the proliferation-inducing ligand (APRIL, also known as TNFSF13A).

MCE designs a unique collection of 943 autoimmune disease-related compounds, covering multiple targets and subtypes, such as TNF Receptor, IFNAR, JAK, Btk, TLR, IL-6, IL-17, IL-23, etc. It is a useful tool for screening autoimmune disease drugs.

Neurodegenerative diseases are characterised by progressive dysfunction and death of neurons, such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis (MS). Neuroprotection is an approach to preserve neurons so that neurons cannot be hurt by different pathological factors in neurodegenerative diseases. Neuroprotectors are some agonists and antagonists targeting some key targets in neuroprotactive signal pathways, such as calcium and sodium channel blockers, GABA receptor agonists, NMDA receptor Antagonists, etc. Current neuroprotectors cannot reverse existing damage, but they may protect against further nerve damage and slow down any degeneration of the central nervous system (CNS) and still play important roles in the treatment of neurodegenerative diseases.

MCE offers a unique collection of 1,719 compounds with potential neuroprotective activities. These compounds mainly act on some key targets in neuroprotetive signal pathways, such as calcium channel, sodium channel, adenosine A1 receptor, etc. MCE Neuroprotective Compopund Library is a useful tool in neuroprotective drug discovery.

From target identification to clinical research, traditional drug discovery and development is a time-consuming and costly process, which also bears high risk. Compared with traditional drug discovery, drug repositioning or repurposing, also known as old drugs for new uses can greatly shorten the development cycle and reduce development cost, which has become a new trend of drug development. After undergoing clinical trials, approved drugs have identified bioactivities, good pharmacokinetic characteristics and safety, which can greatly improve the success rate of drug discovery. A number of successes have been achieved, such as metformin for type 2 diabetes and thalidomide for leprosy and multiple myeloma, etc.

MCE provides a unique collection of 1,495 China NMPA (National Medical Products Administration) approved compounds, which have undergone extensive preclinical and clinical studies and have well-characterized bioactivities, safety and bioavailability properties. MCE NMPA-Approved Drug Library is a good tool for drug repurposing which could dramatically accelerate drug development.

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 Lead-like Covalent Screening Library offers a valuable resource of 1,049 lead-like compounds with commonly used covalent warheads. These warheads, such as acrylamide, activated terminal alkyne, acyloxymethyl ketone, and boronic acid, are capable of reacting with specific amino acid residues, including cysteine, lysine, serine, and histidine. The inclusion of these reactive warheads in the library allows researchers to explore the potential of covalent inhibition, a powerful approach in drug discovery.

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 118 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.

Liver cancer is one of the leading malignancies which occupies the second position in cancer deaths worldwide, becoming serious threat to human health. Hepatocellular carcinoma (HCC), also known as hepatoma is the most common type accounting for approximately 90% of all liver cancers.

Current evidence indicates that during hepatocarcinogenesis, two main pathogenic mechanisms prevail: (1) cirrhosis associated with hepatic regeneration after tissue damage caused by hepatitis infection, toxins or metabolic influences, and (2) mutations occurring in single or multiple oncogenes or tumor suppressor genes. Both mechanisms have been linked with alterations in several important cellular signaling pathways. These include the RAF/MEK/ERK pathway, PI3K/AKT/mTOR pathway, WNT/b-catenin pathway, insulin-like growth factor pathway, c-MET/HGFR pathway , etc.

MCE offers a unique collection of 2,805 compounds with identified and potential anti-liver cancer activity. MCE anti-liver cancer compound library is a useful tool for anti-liver cancer drugs screening and other related research.

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 7,213 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.

On May 15, 2024, "Dimerization and antidepressant recognition at noradrenaline transporter" was published online by Nature. The research findings were an effort from Shanghai Institute of Materia Medica, Chinese Academy of Sciences. This study unraveled the important neural system target - the noradrenaline transporter (NET), obtaining the binding modes of human NET homodimers with the natural substrate norepinephrine (NE) and six selective antidepressants. It laid an important theoretical foundation for understanding the physiological regulation mechanisms of NET and other monoamine transporters.

The Norepinephrine Transporter (NET) Compound Library is obtained by computer-aided virtual screening based on the HY-L901 compound library . The specific screening process includes molecular docking screening, key pharmacophore screening, and CNS-MPO screening, which can be used for new drug discovery targeting the noradrenaline transporter.

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.

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 1,030 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.

Mutations in oncogenes and tumor suppressor genes can modify multiple signaling pathways and in turn cell metabolism, which facilitates tumorigenesis. The paramount hallmark of tumor metabolism is “aerobic glycolysis” or the Warburg effect, coined by Otto Warburg in 1926, in which cancer cells produce most of energy from glycolysis pathway regardless of whether in aerobic or anaerobic condition. Usually, cancer cells are highly glycolytic (glucose addiction) and take up more glucose than do normal cells from outside. The increased uptake of glucose is facilitated by the overexpression of several isoforms of membrane glucose transporters (GLUTs). Likewise, the metabolic pathways of glutamine, amino acid and fat metabolism are also altered. Recent trends in anti-cancer drug discovery suggests that targeting the altered metabolic pathways of cancer cells result in energy crisis inside the cancer cells and can selectively inhibit cancer cell proliferation by delaying or suppressing tumor growth.

MCE provides a unique collection of 3,516 compounds which cover various tumor metabolism-related signaling pathways. These compounds can be used for anti-cancer metabolism targets identification, validation as well anti-cancer drug discovery.

Research has shown that drugs targeting aging pathways demonstrate promising potential in models of age-related diseases such as Alzheimer's disease, cardiovascular diseases, metabolic syndrome, osteoarthritis, and various malignancies. This suggests that intervening in the biological processes of aging may enable synergistic prevention and treatment of multiple chronic diseases. Against the backdrop of the gradual elucidation of core aging mechanisms-including cellular senescence, telomere attrition, epigenetic dysregulation, and chronic inflammation anti-aging research has shifted from traditional phenotypic interventions toward targeting key pathways that regulate biological age.

The MCE Anti-Aging Compound Library Mini is precisely built upon this cutting-edge concept. It focuses on aging-related targets validated through genetic or functional studies, comprising 381 compounds designed to provide systematic research tools for aging biology and intervention strategy development. The library covers core mechanisms such as mTOR, SIRT, energy metabolism, clearance of senescent cells, optimization of mitochondrial function, and telomere maintenance. For each target, 1-5 compounds with clear activity and strong representativeness have been carefully selected, spanning the entire translational spectrum from preclinical tool molecules to clinically investigational drugs.

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.

With the aging population and increasing competitive pressures, neurodegenerative diseases of the central nervous system (CNS) have become a serious medical challenge in modern society, including Parkinson's disease, Alzheimer's disease, brain tumors, and multiple sclerosis. However, the success rate of CNS drug development remains remarkably low, primarily due to the blood-brain barrier (BBB). The blood-brain barrier (BBB) is a semipermeable barrier structure that surrounds the microvasculature of the CNS. In capillaries, the wedged endothelial cells are tightly packed and wedge-shaped, lining the interior of the vessels to form extensive tight junctions. Along with a range of receptors, transporters, efflux pumps, and other cellular components, this barrier regulates the entry and exit of molecules between the bloodstream and the brain. The intact BBB blocks the passage of most blood-borne substances into the brain, preventing nearly 100% of large-molecule drugs and over 98% of small-molecule drugs from entering. Compared to non-CNS drugs, physicochemical properties such as hydrogen bonds, lipophilicity, and molecular weight significantly influence a compound's ability to cross the BBB. Using artificial intelligence (AI) algorithms to predict BBB permeability, a predicted value greater than 0.75 indicates that the compound has strong potential to cross the BBB, providing a promising starting point for CNS drug discovery.

Natural products are an attractive source with varied structures that exhibit potent biological activities, and desirable pharmacological profiles. The core scaffold of a natural product can also provide a biologically validated framework upon which to display diverse functional groups. Inspired by bioactive natural products, natural product-like compounds, occupying the same chemical space, are ideally suited to explore and to facilitate understanding of biological pathways.

MCE 10K Natural Product-like Compound Library consists of 10,000 natural product-like compounds. Each compound has scaffold of natural products or Tanimoto coefficient >0.6 with natural products. The natural-likeness scoring of these compounds is >-2. What’s more, compounds in the library are drug-like and readily available for re-supply, making it a powerful tool for new drug research and development. It can be widely applied in high-throughput screening (HTS) and high-content screening (HCS).

Natural products are an attractive source with varied structures that exhibit potent biological activities, and desirable pharmacological profiles. The core scaffold of a natural product can also provide a biologically validated framework upon which to display diverse functional groups. Inspired by bioactive natural products, natural product-like compounds, occupying the same chemical space, are ideally suited to explore and to facilitate understanding of biological pathways.

MCE 5K Natural Product-like Compound Library consists of 5,000 natural product-like compounds. Each compound has scaffold of natural products or Tanimoto coefficient >0.6 with natural products. The natural-likeness scoring of these compounds is >-2. What’s more, compounds in the library are drug-like and readily available for re-supply, making it a powerful tool for new drug research and development. It can be widely applied in high-throughput screening (HTS) and high-content screening (HCS).

Boronic acid and boronic ester represent a relatively novel and promising chemical structure in drug design. Boronic acid exists in an sp²-hybridized state, possessing an empty p-orbital that can act as a Lewis acid to accept lone pairs from heteroatoms (O, N, or S). This Lewis acidity enables it to form reversible covalent bonds with amino acid residues such as lysine, serine, threonine, and histidine. Currently, five FDA-approved drugs containing boronic acid or boronic ester predominantly involve such covalent binding mechanisms in their interactions with target proteins. Furthermore, boronic acid can serve as a bioisostere for carboxylic acids, phosphates, and phenolic groups, utilized to improve pharmacokinetic properties and enhance drug efficacy.

To date, five boron-containing drugs have been approved by the FDA. The unique properties of boronic acids and boronic esters confer significant potential in drug design, with applications spanning cancer therapy (e.g., multiple myeloma), anti-infectives (e.g., fungal infections, tuberculosis), anti-inflammatory treatments (e.g., atopic dermatitis), antibacterial agents (e.g., carbapenem-resistant bacterial infections), and Reactive Oxygen Species (ROS)-responsive prodrugs, among others. The MCE Boronic Acid/Boronic Ester Fragment Library, which contains 1,488 compounds, serves as a valuable tool for the development of boron-containing drugs.

Protein lactylation, an emerging post-translational modification identified in recent years, plays a critical role in linking cellular metabolic reprogramming, epigenetic regulation, and signaling networks. Based on a systematic framework encompassing lactate metabolism, lactylation, and downstream signaling pathways, this compound library comprehensively targets multiple regulatory layers, including histone modification enzymes (such as p300 and HDACs), key glycolytic enzymes (such as PKM2, LDHA, and GAPDH), transcriptional regulators (such as STAT3, HMGB1, and p53), as well as central signaling pathway nodes including HIF-1α, NF-κB, and PI3K-AKT-mTOR. This integrated design enables a comprehensive representation of the regulatory roles of lactylation across the “metabolism–epigenetics–signaling” axis.

MCE has assembled a collection of 5,793 known bioactive compounds and potential functional molecules, making this library suitable for a wide range of applications, including high-throughput drug screening, inhibitor identification, and mechanistic studies. It can be used to systematically evaluate the functional roles of lactylation in biological processes such as tumor metabolism, immune regulation, and inflammatory responses, and to efficiently identify small-molecule candidates with regulatory potential, thereby facilitating the development of innovative therapeutics targeting the interplay between metabolism and epigenetic regulation.

Neuronal Signaling is involved in the regulation of the mechanisms of the central nervous system (CNS) such as its structure, function, genetics and physiology as well as how this can be applied to understand diseases of the nervous system. Every information processing system in the CNS is composed of neurons and glia, neurons have evolved unique capabilities for intracellular signaling (communication within the cell) and intercellular signaling (communication between cells). G protein-coupled receptors (GPCRs), including 5-HT receptor, histamine receptor, opioid receptor, etc. are the largest class of sensory proteins and are important therapeutic targets in Neuronal Signaling. Besides, Notch signaling, such as β- and γ-secretase, also plays multiple roles in the development of the CNS including regulating neural stem cell (NSC) proliferation, survival, self-renewal and differentiation. GPCR dysfunction caused by receptor mutations and environmental challenges contributes to many neurological diseases. Notch signaling in neurons, glia, and NSCs is also involved in pathological changes that occur in disorders such as stroke, Alzheimer's disease and CNS tumors. Thus, targeting Neuronal Signaling, such as notch signaling and GPCRs, can be used as therapeutic interventions for several different CNS disorders.

MCE designs a unique collection of 3,747 Neuronal Signaling-related compounds that act as a useful tool for the research of neuronal regulation and neuronal diseases.

Withdrawal or delisting drugs refer to drugs that are recalled or discontinued from the market due to low efficiency, serious side effects, financial and regulatory problems and other reasons. Once the drug is withdrawn from the market, it will cause heavy losses to the original research company that invested a lot of time, finance and other costs to develop the drug.

Adverse drug reaction (ADR) is the main reason for drug withdrawal from the market. ADR refers to the unexpected effects caused by the reasons such as the target-directed interaction during the treatment. However, studying the mechanism of these ADRs may just be a breakthrough in finding new indications. For example, thalidomide, the protagonist of the drug damage event that caused numerous "seal babies" deformed infants, was found to be due to the degradation of a transcription factor - SALL4 after delisting, which made thalidomide have a new clinical application. In 1998, it was approved by FDA for the treatment of leprosy nodular erythema, and in 2006, it was approved for the treatment of multiple myeloma. ADR study of delisted drugs can not only avoid the loss of drug development in advance but also bring hope to new indications.

MCE has sorted out 231 drug compounds withdrawn from the market through FDA, EMA and other authoritative platforms. Each compound has withdrawal records in at least one country/market. It is a useful tool for conducting research on drug side effects or drug toxicity mechanisms and discovering new indications of drugs.

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.

G protein-coupled receptors (GPCRs) are membrane proteins in humans and one of the most important targets in drug discovery. Approximately 35% of launched drugs are targeted GPCRs, making them a crucial class of targets in drug discovery.

The orthosteric site of a GPCR is its endogenous ligand’s (such as neurotransmitters or hormones) binding site. This site plays a central role in signal transduction. Small molecules binding to this site typically contain a protonatable amino group, enabling the formation of salt bridges or hydrogen bonds with acidic residues in the binding pocket. In contrast, the allosteric site does not directly initiate signaling but modulates the signal intensity of the GPCR by altering or stabilizing the conformation of the orthosteric site. Small molecules binding to the allosteric site often contain multiple aromatic rings to occupy hydrophobic pockets and achieve their functional effects.

MCE has collected over 7,115 reported bioactive molecules targeting GPCRs, covering Class A, B, and C GPCRs. These small molecules were subjected to AI representation to extract 2D and 3D features. Subsequently, we do screening by AI score based on similarity to identify molecules in diversity library highly similar to the reported bioactive molecules in both 2D and 3D, with a threshold greater than 0.7. Further screening based on cLogP was applied to select molecules with good lipophilicity, which facilitates the binding of small molecules to GPCRs. This diversity library can be widely applied to the discovery of compounds targeting GPCR proteins.