Small molecules

Glycomimetics are designed to mimic the structure of natural carbohydrates and modulate their disease-related functions. Macrocyclic glycomimetics are an extremely interesting class of glycomimetics as they occupy space between small and macro molecules. Macrocyclic glycomimetics are mostly represented by naturally occurring molecules derived from marine microorganisms and bacterial or fungal metabolites.

GPCRs are a large family of cell surface receptors that respond to a variety of external signals. Binding of a signaling molecule to a GPCR results in G protein activation, which in turn triggers the production of any number of second messengers. GPCRs play an important role in the human body, and increased understanding of these receptors has greatly affected modern medicine. In fact, researchers estimate that between one-third to one-half of all approved drugs act by binding to GPCRs. GPCRs are a large group of drug targets in drug discovery.

MCE provides a unique collection of 2,420 small molecules targeting GPCRs that can be used in the screening for various GPCRs-related research and drug development projects.

Metabolism is the set of life-sustaining chemical reactions in organisms. Metabolic pathways are enzyme-mediated biochemical reactions that lead to biosynthesis (anabolism) or breakdown (catabolism) of natural product small molecules within a cell or tissue. Acting as catalysts, enzymes are crucial to metabolism - they allow a reaction to proceed more rapidly - and they also allow the regulation of the rate of a metabolic reaction. Proteases are used throughout an organism for various metabolic processes. Proteases control a great variety of physiological processes that are critical for life, including the immune response, cell cycle, cell death, wound healing, food digestion, and protein and organelle recycling. Imbalances in metabolic activities have been found to be critical in a number of pathologies, such as cardiovascular diseases, inflammation, cancer, and neurodegenerative diseases.

MCE designs a unique collection of 4,571 Metabolism/Protease-related small molecules that act as a useful tool for drug discovery of metabolism-related diseases.

An emerging drug design method is based on the secondary binding site effect, where small molecule drugs are designed to bind to secondary binding sites on target biomolecules rather than primary orthomorphic sites. Successful potential drugs (known as allosteric modulators) will be able to bind to allosteric sites and remotely alter (or modify) the conformation of the main orthosteric binding sites of biological targets. Allosteric modulators (AMs) are ligands of proteins that act through binding sites different from natural (orthosteric) ligand sites. AMs are relatively small, more lipophilic, and more rigid compounds. The binding efficacy of AMs with their targets is often slightly lower. AMs are divided into positive AMs (PAMs) and negative AMs (NAMs). AMs are ideal drug targets because they can fine-tune receptor activity while preserving the spatial and temporal signal transduction characteristics of endogenous ligands, resulting in fewer targeted side effects, improved subtype selectivity, and better promotion of biased signal transduction than normal ligands.

MCE designs a unique collection of 183 small allosteric modulators. It is a good tool to be used for research on metabolize, cancer and other diseases.

Bioactive small molecules are important sources of lead compounds and effective tools for drug screening. Because the target of active small molecules is clear, it is conducive to the study of mechanism. In addition, due to the large structural differences between the individual active molecules, it is easier to obtain a greater variety of lead compounds.

MCE integrates the Bioactive Compound Library (HY-L001) and Novel Bioactive Compound Library (HY-L111) to form the Bioactive Compound Library Max. Bioactive Compound Library Max contains novel active small molecules, molecules that have entered the clinical stage and the market, and small molecules that have been verified by cell experiments or biochemical experiments, which fundamentally expands the number of compound libraries in the library and improves the structural diversity, and is an effective tool to start drug screening and mechanism research.

MCE can provide a library of 20,819 mitophagy compounds, which can be used for drug development and mechanism research in cancer, immunity, infection and other hot research fields.

Epigenetics refers to changes in phenotype that are not rooted in DNA sequence. Many types of epigenetic processes have been identified, including DNA methylation, alteration in the structure of histone proteins and gene regulation by small noncoding microRNAs. Modification of DNA, protein, or RNA, resulting in changes to the function and/or regulation of these molecules, without altering their primary sequences, reveals the complexities of cellular differentiation, embryology, the regulation of gene expression, aging, cancer, and other diseases.

MCE provide a unique collection of 1,247 epigenetics-related compounds that can be used in the research of the related diseases.

Extracellular vesicles (EVs) are small membrane binding structures that are released from cells into the surrounding environment and play a crucial role in mediating and regulating intercellular communication related to physiological and pathological processes. EVs are lipid membrane vesicles composed of proteins, lipids, and nucleic acids. EVs can be divided into several types based on their source, such as extracellular vesicles, microcapsules, and apoptotic vesicles. The size range of exosomes is 30-150nm, which are endocrine in multi vesicular endosomes (MVEs); microvesicles (50-1000nm) are secreted directly through extracellular interactions, thereby releasing plasma membrane vesicles. In contrast, apoptotic bodies are usually larger, ranging in size from 1 to 5 μ m. This is generated during programmed cell death. EV plays a crucial role in transmitting information between cells and influencing the behavior and function of receptor cells.

MCE designs a unique collection of 411 small molecules related to extracellular vesicles (EVs). It is a good tool to be used for research on metabolize, cancer and other diseases.

Ion channel is a membrane-binding enzyme whose catalytic site is an ion conduction pore, which is opened and closed in response to specific environmental stimuli (voltage, ligand concentration, membrane tension, temperature, etc.). Ion channel provide pores for the passive diffusion of ions on the biofilm. Due to their high selectivity for ion, ion channel are generally classified as sodium (Na⁺ ), potassium (K⁺ ), calcium (Ca²⁺ ), chloride (Cl^- ), and non-specific cation channel. Ion channel is an important contributor to cell signal transduction and homeostasis. In addition to electrical signal transduction, ion channel also have many functions: regulating vascular smooth muscle contraction, maintaining normal cell volume, regulating glandular secretion, protein kinase activation, etc. Therefore, dysfunction of ion channel can lead to many diseases, and its mechanism research is particularly important.

MCE designs a unique collection of 1,175 small molecules related to ion channel, mainly targeting Na⁺ channel, K⁺ channel, Ca²⁺ channel, GABA receptor, iGluR, etc. It is an essential tool for research of cardiovascular diseases, Nervous system diseases and other diseases.

Immuno-Oncology is a type of immunotherapy that has the specific purpose of treating cancer. It works by stimulating our immune system to fight back. Normally, our immune system is able to destroy cancer cells in our body, however sometimes cancer cells can adapt and mutate, effectively hiding from our immune system. This is when tumors can develop and become a threat to our health. Immuno-oncology involves mobilizing lymphocytes to recognize and eliminate cancer cells using the body’s immune system. There are several immuno-oncology treatments available, including Immune cell therapy (CAR-T), monoclonal antibodies (mABs) and checkpoint inhibitors, cytokines and cancer vaccines.

MCE Small Molecule Immuno-Oncology Compound Library offers 494 bioactive tumor immunology compounds that target some important checkpoints such as PD1/PD-L1, CXCR, Sting, IDO, TLR, etc. This library is a useful tool for Immuno-oncology research.

The developmental proteins Hedgehog, Notch and Wnt are key regulators of cell fate, proliferation, migration and differentiation in several tissues. Their related signaling pathways are frequently activated in tumors, and particularly in the rare subpopulation of cancer stem cells. The Wnt signaling pathway is a conserved pathway in animals. Deregulated Wnt signaling has catastrophic consequences for the developing embryo and it is now well appreciated that defective Wnt signaling is a causative factor for a number of pleiotropic human pathologies, including cancer. Hedgehog signaling pathway is linked to tumorigenesis and is aberrantly activated in a variety of cancers. The Notch signaling pathway is a highly conserved cell signaling system present in most animals. It plays an important role in cell-cell communication, and further regulates embryonic development.

MCE designs a unique collection of 371 Wnt/Hedgehog/Notch signaling pathway-related small molecules. Wnt/Hedgehog/Notch Compound Library serves as a useful tool for stem cell research and anti-cancer drug screening.

Targeted cancer therapies are drugs or other substances that block the growth and spread of cancer by interfering with specific molecular targets that are involved in the growth, progression, and spread of cancer.

There are several different types of targeted therapy. The most common types are small-molecule drugs and monoclonal antibodies. Small-molecule drugs are small enough to enter cells easily, so they are used for targets that are inside cells, while monoclonal antibodies are usually used for targets that are located outside the cells. Because of high specificity, low side effect and potent anticancer activity, targeted therapy has become the mainstream of new anti-tumor drugs. Various targeted therapies have been approved by FDA and used in the treatment of diseases.

MCE carefully collects a unique of 107 targeted therapy drugs used in cancer treatment. MCE Targeted therapy drug library is a useful tool for the research of targeted therapy.

Dopamine receptor (DAR), widely distributed in the brain, plays a key role in regulating motor function, motivation, driving force and cognition. The role of DA is mediated by D1-type (D1, D5) and D2-type receptors (D2S, D2L, D3, D4), which are distributed in presynaptic, postsynaptic and extrasynaptic, projection neurons and interneurons. Each receptor has a different function. D1 and D5 receptors couple with G stimulation sites and activate Adenylyl cyclase. The activation of Adenylyl cyclase leads to the production of the second messenger cAMP, which leads to the production of protein kinase A (PKA), which leads to further transcription in the nucleus. D2 to D4 receptors are coupled to G inhibitory sites to inhibit adenylyl cyclase and activate potassium Ion channel. These receptors utilize phosphorylation cascades or direct membrane interactions to affect the functions of voltage-gated and neurotransmitter-gated channels, cytoplasmic enzymes, and transcription factors. Dopamine receptor plays an important role in daily life.

MCE designs a unique collection of 203 small molecules related to dopamine receptor. It is a good tool for screening drugs from nervous system disease.

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 1,491 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.

Macrocycles, molecules containing 12-membered or larger rings, are receiving increased attention in small-molecule drug discovery. The reasons are several, including providing access to novel chemical space, challenging new protein targets, showing favorable ADME- and PK-properties. Macrocycles have demonstrated repeated success when addressing targets that have proved to be highly challenging for standard small-molecule drug discovery, especially in modulating macromolecular processes such as protein–protein interactions (PPI). Otherwise, the size and complexity of macrocyclic compounds make possible to ensure numerous and spatially distributed binding interactions, thereby increasing both binding affinity and selectivity.

MCE offers a unique collection of 387 macrocyclic compounds which can be used for drug discovery for high throughput screening (HTS) and high content screening (HCS). MCE Macrocyclic Compound Library is a useful tool for discovering new drugs, especially for “undruggable” targets and protein–protein interactions.

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 2,155 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.

Nuclear factor-κB (NF-κB)/Rel proteins include NF-κB2 p52/p100, NF-κB1 p50/p105, c-Rel, RelA/p65, and RelB. These proteins function as dimeric transcription factors that regulate the expression of genes and influence a broad range of biological processes including innate and adaptive immunity, inflammation, stress responses, B-cell development, and lymphoid organogenesis. NF-κB plays a key role in regulating the immune response to infection. In addition, activation of the NF-κB pathway is involved in the pathogenesis of chronic inflammatory diseases, such as asthma, rheumatoid arthritis, and inflammatory bowel disease. Incorrect regulation of NF-κB has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development.

MCE owns a unique collection of 860 small molecule compounds that can be used in the research of NF-κB signaling pathway or high throughput screening (HTS) related drug discovery.

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 1,660 small molecules including identified covalent inhibitors and other bioactive molecules having common covalent reactive groups as warheads, such as acrylamides, activated terminal acetylenes, Sulfonyl fluorides/esters, cloracetamides, alkyl halides, epoxides, aziridines, disulfides, etc.

Covalent inhibitors are small molecules that can bind specifically to target proteins through covalent bonds and inhibit their biological functions. Although for a long time, covalent targeting has been playing a subordinate role in drug discovery, with an increasing number of reports on successful clinical applications of such drugs, the potential of these agents is now being acknowledged.

Covalent ligands rely on reactive groups (“warheads”), and new warheads are key to expanding the scope of covalent modalities. 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 8,900 fragment molecules with covalent modification potential, which can target various reactive amino acid residues and can be used for fragment-based covalent drug discovery.

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 2,971 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.

Proteolysis-targeting chimera (PROTAC) has been developed to be a useful technology for targeted protein degradation. PROTACs consist of a ligand for E3 ligase (E3 ligase binder), a linker and a ligand (mostly small-molecule inhibitor) for protein of interest（target binder）. Upon binding to the target protein, the PROTACs can recruit E3 for target protein ubiquitination, which is subjected to proteasome-mediated degradation.

Although there are more than 600 E3 ubiquitin ligases, only several with small molecule ligands have been used for designing PROTACs, including Skp1-Cullin-F box complex containing Hrt1 (SCF), Von Hippel-Lindau tumor suppressor (VHL), Cereblon (CRBN), inhibitor of apoptosis proteins (IAPs), and mouse double minute 2 homolog (MDM2).

MCE carefully prepared a unique collection of 52 ligands for E3 ligase, which have been reported to be used in PROTAC design. MCE E3 ligase ligand library is a useful tool for PROTAC development.

MCE Targeted Diversity Library contains 2,206 compounds, covering more than 1000 targets and isoforms, such as GPCRs, Ion channel, variety of kinases, etc. 1-3 compounds with high potency and selectivity were carefully selected for each target and isoform. The bioactivity information of each compound has been clearly reported in the literatures. This library is a concise collection of small molecule compounds with comprehensive target coverage, which can be used for phenotypic screening at low cost.

Metabolism is the set of life-sustaining chemical reactions in organisms that maintain cell homeostasis. Metabolic pathways are enzyme-mediated biochemical reactions that lead to biosynthesis (anabolism) or breakdown (catabolism) of molecules including glucose metabolism, lipid metabolism and amino acid or protein metabolism within a cell or tissue. As catalysts, enzymes are crucial to metabolism as they allow a reaction to proceed more rapidly and tregulate the rate of a metabolic reaction. Due to the importance of metabolic balance in the organism, the abnormal function of metabolic enzymes often leads to the occurrence of a variety of metabolic diseases, such as diabetes, obesity, cardiovascular disease, etc.

MCE designs a unique collection of 2,911 metabolic enzymes related small molecules, which is an important tool for studying the metabolic activities of organisms and developing drugs for metabolic diseases.

Natural products are small molecular compounds that occur in nature and come from any organism, including primary and secondary metabolites. Natural products have potential biological activity and can be used as lead compounds for drug discovery. Nature has been a source of medicines for thousands of years, and a large number of drugs have been isolated from nature, many based on their use in traditional medicine. With the development of compound targets, there is an increasing need to screen for compound diversity. Through ongoing research into natural biodiversity, much of which remains to be exploited, natural products will play a key role in meeting this demand. The Lipinski rule of 5 is used to describe the drug-like properties of a molecule, molecules that adhere to the rule of 5 have higher drug potential. Based on MCE natural product library, MCE selects the molecules that obey the rule of 5, which makes the efficiency of drug screening higher.

MCE designs a unique collection of 2,711 RO5 drug-like natural products, which is an important tool for drug discovery.

Membrane receptors, also known cell surface receptors or transmembrane receptors, are transmembrane proteins embedded into the plasma membrane which play an essential role in maintaining communication between the internal processes within the cell and various types of extracellular signals. They act in cell signaling by receiving (binding to) extracellular molecules, which are also called ligands. These extracellular molecules include hormones, cytokines, growth factors, neurotransmitters, lipophilic signaling molecules such as prostaglandins, and cell recognition molecules.

There are three kinds of membrane receptors: ion channel-linked receptors, enzyme-linked receptors and G-protein-linked receptors. They play important roles in keeping human normal physiologic processes. GPCRs and ion channels are important drug targets in drug discovery.

MCE provides a unique collection of 4,849 compounds targeting a variety of membrane receptors. MCE Membrane reeptor-targeted Compound Library can be used for membrane receptor-focused screening and drug discovery.

A membrane protein is a protein molecule that is attached to or associated with the membrane of a cell or an organelle. Membrane proteins can be classified into two groups based on how the protein is associated with the membrane: integral membrane proteins and peripheral membrane proteins. In humans, about 30% genome encodes membrane proteins. Membrane proteins perform a variety of functions vital to the survival of organisms, for example, signal transduction, molecules or ion transportation, enzymatic catalysis, and intercellular communication. Membrane proteins also play important roles in drug discovery. As reported, more than 60% of current drug targets are membrane proteins.

MCE supplies a unique collection of 7,126 compounds targeting a variety of membrane proteins. MCE Membrane Protein-targeted Compound Library can be used for membrane protein-focused screening and drug discovery.

Bioactive compounds are a general term for a class of substances that can cause certain biological effects in the body, which are the main source of small molecule drugs. These compounds generally penetrate cell membranes, act on specific target proteins in cells, regulate intracellular signaling pathways, and cause some changes in cell phenotype.

MCE owns a unique collection of 19,569 compounds with confirmed biological activities and clear targets. These compounds include natural products, innovative compounds, approved compounds, and clinical compounds. These can also be used for signal pathway research, drug discovery and drug repurposing, etc.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide and is the primary liver manifestation of metabolic syndrome. The growth of NAFLD has coincided with the obesity epidemic. NAFLD is composed of excess lipid accumulation in the liver, causing steatotoxicity, and shows a wide range of histopathological abnormalities. NAFLD may progress from simple steatosis to Non-alcoholic steatohepatitis (NASH) with or without fibrosis (NASH), and eventually to cirrhosis and hepatocellular carcinoma. To date, very few drugs have been approved for marketing specifically for the treatment of NAFLD, so increased efforts to develop NAFLD drugs are necessary.

MCE designs a unique collection of 3,108 small molecules with definite or potential anti-NAFLD activity, which is an important tool for studying the pathological mechanism of NAFLD and developing drugs for NAFLD.

Amino acids, as one of the most fundamental organic compounds in living organisms, serve not only as the basic building blocks of proteins but also but also undertake the functions of energy supply, neurotransmitter synthesis, and maintenance of internal environment stability.Amino acid metabolic enzymes are a class of enzymes involved in the metabolic processes of amino acids, catalyzing their synthesis, breakdown, transformation, and interactions with other metabolic pathways. Abnormalities in amino acid metabolic enzymes can lead to various metabolic diseases, such as phenylketonuria and hyperammonemia, etc. Therefore, actively exploring and regulating the processes of amino acid metabolism is crucial for the development of drugs related to these diseases.

MCE designs a unique collection of 220 small molecules target amino acid metabolizing enzymes, which is an important tool for studying studying amino acid metabolism processes or metabolism-related drug development.

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

Hematopathy, also known as hematopoietic system diseases, are a class of diseases that hematopoietic system has abnormal changes. Common hematopathy include: aplastic anemia, myeloproliferative diseases, thalassemia, leukemia, lymphoma, myeloma and hemophilia, etc. In recent years, treatments for hematopathy have been developed. In particular, the treatment of malignant hematopathy developed from chemotherapy, radiotherapy, bone marrow development to immunotherapy, induced differentiation therapy, cell therapy, gene therapy and hematopoietic stem cell transplantation. Although these therapies have greatly improved the survival rate of patients, there are still problems such as low cure rate and easy recurrence in the treatment of hematopathy. Therefore, it is of great significance to actively search for new hematopathy therapeutic drugs.

MCE designs a unique collection of 2,757 anti-hematopathy small molecules, which is an effective tool for development and research of anti-hematopathy compounds.

Exosomes are small membrane vesicles of endocytic origin that are secreted by most cells in culture. Exosomes contain nucleic acids, proteins, lipids, amino acids, and metabolites, etc. Their diverse constituents can reflect their cell of origin. Exosomes are associated with immune responses, viral pathogenicity, pregnancy, cardiovascular diseases, central nervous system-related diseases, and cancer progression. Proteins, metabolites, and nucleic acids delivered by exosomes into recipient cells effectively alter their biological response. Such exosome-mediated responses can be disease promoting or restraining.

The biology of exosomes in disease is still emerging, and the number of studies addressing their utility in the diagnosis and treatment of various pathologies has increased substantially. MCE supplies a unique collection of 45 compounds with the activity of inhibiting or stimulating exsomes secretion/biosynthesis. MCE Exosomes Compound Library is a useful tool for exsomes research.

Covalent inhibitors are small molecules that can bind specifically to target proteins through covalent bonds and inhibit their biological functions. Although for a long time, covalent targeting has been playing a subordinate role in drug discovery, with an increasing number of reports on successful clinical applications of such drugs, the potential of these agents is now being acknowledged. Currently, cysteine is the most common covalent amino acid residue in a variety of covalent drugs, and various warheads have been developed that can react with cysteine, providing the key building blocks for covalent drugs to form covalent bonds.

To meet the development needs of covalent inhibitors targeting cysteine, MCE has designed a unique collection of 4,827 compounds with different covalent warheads that target cysteine. The MCE Cysteine Targeted Covalent Library is designed using the following covalent warheads: Acrylamides, Propiolic acid ester, Dimethylamine functionalized acrylamides, Chloroacetamides, Acrylonitrile, 2-Cyanoacrylamide, Aziridine, Haloacetamide, etc.

Gastric Cancer (GC) is one of the most common malignant tumors in the world, ranking fourth in mortality rate globally. Because the early symptoms of stomach neoplasm are usually not obvious, are diagnosed with gastric cancer at terminal stage, and the relative survival rate within 5 years is very low. With the further understanding of the molecular characteristics of stomach neoplasm, many therapeutic targets for gastric cancer have been identified, and molecular targeted therapies such as CTLA-4, HER2 and immune checkpoint inhibitors have made rapid progress. Although survival rates for patients with gastric neoplasm have improved over the past few decades, the prognosis is still worrying. Therefore, there is an urgent need for new drugs to treat gastric cancer.

MCE designs a unique collection of 649 small molecules with definite or potential anti-gastric cancer activity, which is an important tool for studying the pathological mechanism of stomach neoplasm and developing drugs for stomach neoplasm.

Mechanoreceptors convert different stimuli from the outside into electrical signals, enabling us to quickly respond to our environment. Mechanoreceptors are distributed throughout the body, including in the skin, tendons, muscles, joint capsules and viscera. In addition to the channels of TRP and Piezo mentioned in the Nobel Prize, there are also targets such as KCNK, ENaC and ASIC2, which play an important role in the environment perception and homeostasis of living organisms.

MCE offers a unique collection of 265 compounds related to mechanoreceptors, which targeting different mechanoreceptors, such as TRP, Piezo, KCNK, ENaC, etc. MCE mechanoreceptors compound library is a powerful tool for studying mechanoreceptors and life perception.

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 493 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.

Protein ubiquitination is an enzymatic post-translational modification in which an ubiquitin protein is attached to a substrate protein. Ubiquitination involves three main steps: activation, conjugation, and ligation, performed by ubiquitin-activating enzymes (E1s), ubiquitin-conjugating enzymes (E2s), and ubiquitin ligases (E3s), respectively. Ubiquitination affects cellular processes such as apoptosis, cell cycle, DNA damage repair, and membrane transportation, etc. by regulating the degradation of proteins (via the proteasome and lysosome), altering the cellular localization of proteins, affecting proteins activity, and promoting or preventing protein-protein interactions. Deregulation of ubiquitin pathway leads to many diseases such as neurodegeneration, cancer, infection and immunity, etc.

MCE offers a unique collection of 253 small molecule modulators with biological activity used for ubiquitination research. Compounds in this library target the key enzymes in ubiquitin pathway. MCE Ubiquitination Compound Library is a useful tool for the research of ubiquitination regulation and the corresponding diseases.

Chemical probes are simply reagents with high potency, selectivity and cell-permeability which play important roles in both fundamental and applied biological research. In their most common application, chemical probes can establish the tractability of a specific target. They are used to interrogate the relationship between a target and its phenotype (biological tractability) as well as an ability to modulate that phenotype using a small molecule. Otherwise, chemical probes also have had a major impact in enabling and accelerating discoveries along the path to pioneer medicines. They have helped to improve the understanding of targets and pathways and have created opportunities for proprietary drug discovery efforts to an extent that would not have been possible otherwise.

MCE provides a unique collection of 268 chemical probes with high potency (at least 100 nM potency), selectivity (at least 10-fold selectivity against any other target) and cell-permeability (at least 10 μM potency). MCE Chemical probe library is a useful tool for target identification and mechanism research.

Natural products are small molecules produced naturally by any organism including primary and secondary metabolites. Natural sources may lead to basic research on potential bioactive components for commercial development as lead compounds in drug discovery.

Nature has been a source of medicinal agents for thousands of years, and an impressive number of modern drugs have been isolated from natural sources, many based on their use in traditional medicine. With the development of new molecular targets, there is an increasing demand for novel molecular diversity for screening. Natural products will play a crucial role in meeting this demand through the continued investigation of world’s bio-diversity, much of which remains unexplored.

MCE provides a unique collection of 4,663 natural compounds that contain Saccharides and Glycosides, Phenylpropanoids, Quinones, Flavonoids, Terpenoids and Glycosides, Steroids, Alkaloid, Phenols, Acids and Aldehydes. Natural Product Library is a useful tool for drug discovery that can be used for high throughput screening (HTS) and high content screening (HCS).

Proteolysis-targeting chimera (PROTAC) has been developed to be a useful technology for targeted protein degradation. PROTACs consist of a ligand for E3 ligase (E3 ligase binder), a linker and a ligand (mostly small-molecule inhibitor) for protein of interest（target binder）. Upon binding to the target protein, the PROTACs can recruit E3 for target protein ubiquitination, which is subjected to proteasome-mediated degradation. Therefore, PROTACs execute their functions by degrading the target proteins rather than inhibiting them, which has a great superiority in overcoming resistance caused by target mutation or overexpression. To date, PROTAC technology has been applied to a variety of targets, including AR, ER, BTK, BET, and BCR-ABL to overcome resistance.

MCE carefully prepared a unique collection of 33 ligands for target proteins, which have been reported to be used in PROTAC design. MCE Target Protein Ligand Library is a useful tool for PROTAC development.

Mitochondria plays an important role in many vital processes in cells, including energy production, fatty-acid oxidation and the Tricarboxylic Acid (TCA) cycle, calcium signaling, permeability transition, apoptosis and heat production. At present, it is recognized that many diseases are associated with impaired mitochondrial function, such as increased accumulation of ROS and decreased OXPHOS and ATP production. Mitochondria are recognized as one of the most important targets for new drug design in cancer, cardiovascular, and neurological diseases, etc. Some small molecule drugs or biologics can act on mitochondria through various pathways, including ETC inhibition, OXPHOS uncoupling, mitochondrial Ca²⁺ modulation, and control of oxidative stress via decrease or increase of mitochondrial ROS accumulation.

MCE supplies a unique collection of 930 mitochondria-targeted compound that mainly targeting Mitochondrial Metabolism, ATP Synthase, Mitophagy, Reactive Oxygen Species, etc. MCE Mitochondria-Targeted Compound Library is a useful tool for mitochondria-targeted drug discovery and related research.

Neurotransmitter (NT) receptors, also known as neuroreceptors, are a broadly diverse group of membrane proteins that bind neurotransmitters for neuronal signaling. There are two major types of neurotransmitter receptors: ionotropic and metabotropic. Ionotropic receptors are ligand-gated ion channels, meaning that the receptor protein includes both a neurotransmitter binding site and an ion channel. The binding of a neurotransmitter molecule (the ligand) to the binding site induces a conformational change in the receptor structure, which opens, or gates, the ion channel. The term “metabotropic receptors” is typically used to refer to transmembrane G-protein-coupled receptors. Metabotropic receptors trigger second messenger-mediated effects within cells after neurotransmitter binding.

In some neurological diseases, the neurotransmitter receptor itself appears to be the target of the disease process. Many neuroactive drugs act by modifying neurotransmitter receptors. A better understanding of neurotransmitter receptor changes in disease may lead to improvements in therapy.

MCE designs a unique collection of 1,877 compounds targeting a variety of neurotransmitter receptors. MCE Neurotransmitter Receptor Compound Library is a useful tool for neurological diseases drug discovery.

Angiogenesis is the physiological process through which new blood vessels are formed from pre-existing vessels. It occurs in various physiological processes e.g. embryonic development, menstrual cycle, exercise and wound healing etc. Angiogenesis is regulated by both endogenous activators and inhibitors. Some key activators of angiogenesis include vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), angiogenin, TGF-β, etc. whereas angiogenesis inhibitors are angiostatin, endostatin, interferon, platelet factor 4, etc. The loss of balance between these opposing signals leads to life threatening diseases like cancer, cardiovascular and ischemic diseases etc. which are thus controlled by exogenous angiogenesis activators (for cardiovascular/ischemic disorders) and inhibitors (for cancer).

MCE offers a unique collection of 2,105 compounds with validated angiogenesis targets modulating properties. MCE angiogenesis-related compound library is an effective tool for angiogenesis research and discovery of angiogenesis-related drugs.

Autophagy is a lysosomal degradation pathway that is essential for cell survival, differentiation, development, and homeostasis. The process of autophagy in mammalian cells is as follows: a portion of cytoplasm, including organelles, is enclosed by a phagophore or isolation membrane to form an autophagosome. The outer membrane of the autophagosome subsequently fuses with the endosome and then the lysosome, and the internal material is degraded. Autophagy plays a wide variety of physiological and pathophysiological roles. Defective autophagy contributes to various pathologies, including infections, cancer, neurodegeneration, aging, and heart disease.

MCE provides a unique collection of 1,403 autophagy pathway-related compounds that is a useful tool for the research of autophagy-related regulation and diseases.

Glucose homeostasis is tightly regulated to meet the energy requirements of the vital organs and maintain an individual’s health. Glucose metabolism includes glycolysis, tricarboxylic acid cycle, pentose phosphate pathway, oxidative phosphorylation and other metabolic pathways. Glucose is the major carbon source that provides the main energy for life. Glucose metabolism dysregulation is also implicated in many diseases such as diabetes, heart disease, neurodegenerative diseases and even cancer.

MCE offers a unique collection of 1,035 compounds related to glucose metabolism, which target glucose metabolism related targets, such as GLUT, Hexokinase, Pyruvate Kinase, IDH, etc. MCE glucose metabolism library is a powerful tool for studying glucose metabolism and drug discovery of diseases related to glucose metabolism.

Lipids are a fundamental class of organic molecules implicated in a wide range of biological processes, and based on this can be broadly classified into five categories: fatty acids, triacylglycerols (TAGs), phospholipids, sterol lipids and sphingolipids. Lipids play a crucial role in different metabolic pathways and cellular functions. Lipid metabolism is an important physiological process that is related to nutrient adjustment, hormone regulation, and homeostasis. Lipid metabolism dysregulation is associated with many diseases such as obesity, liver disease, aging and inflammation.

MCE offers a unique collection of 656 compounds related to lipid metabolism, which target relevant targets in the process of lipid metabolism, such as ATGL, MAGL, FAAH, acetyl-Coa Carboxylase, FASN, etc. MCE lipid metabolism compound library is a useful tool for research lipid metabolism and drug discovery of diseases related to lipid metabolism.

Glycolysis is a series of metabolic processes by which one molecule of glucose is catabolized to two molecules of pyruvate with a net gain of two ATP. Glycolysis takes place in 10 steps and catalyzed by a series of enzyme, such as hexokinase, Glucose-6-phosphate isomerase, Phosphofructokinase, etc. Glycolysis is used by all cells in the body for energy generation.

Most cancer cells exhibit increased glycolysis and use this metabolic pathway for generation of ATP as a main source of their energy supply. This phenomenon is known as the Warburg effect and is considered as one of the most fundamental metabolic alterations during malignant transformation. Because increased aerobic glycolysis is commonly seen in a wide spectrum of human cancers, development of novel glycolytic inhibitors as a new class of anticancer agents is likely to have broad therapeutic applications.

MCE provides a unique collection of 712 glycolysis compounds that mainly target hexokinase, glucokinase, enolase, pyruvate kinase, PDHK, etc. MCE Glycolysis Compound Library is a useful tool for glucose metabolism research and anti-cancer drug discovery.

Endoplasmic reticulum (ER) contributes to the production and folding of approximately one third of cellular proteins, and is thus inextricably linked to the maintenance of cellular homeostasis and the fine balance between health and disease. However, some adverse factors negatively impact ER functions and protein synthesis, resulting in the activation of Endoplasmic reticulum stress (ER stress, ERS) and unfolded protein response (UPR) signaling pathways. The UPR is triggered when ER protein folding capacity is overwhelmed by cellular demand and the UPR initially aims to restore ER homeostasis and normal cellular functions. However, if this fails, then the UPR triggers cell death. Chronic ER stress and defects in UPR signaling are emerging as key contributors to a growing list of human diseases, including diabetes, neurodegeneration and cancer.

MCE Endoplasmic Reticulum Stress Compound Library contains 223 ER stress-related compounds that mainly target PERK, IRE1, ATF6, etc. MCE ER stress library is a useful tool for researching ER stress and related diseases.