molecule

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 594 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.

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 5,648 compounds targeting a variety of membrane receptors. MCE Membrane reeptor-targeted Compound Library can be used for membrane receptor-focused screening and drug discovery.

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.

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 8,357 compounds targeting a variety of membrane proteins. MCE Membrane Protein-targeted Compound Library can be used for membrane protein-focused screening and drug discovery.

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

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

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 2,850 small molecules targeting GPCRs that can be used in the screening for various GPCRs-related research and drug development projects.

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.

Flavor is an expression of smell and taste that is achieved through a variety of chemical processes triggered by molecules. Food flavor is an important attribute of food quality and in some cases determines consumers' food preferences. In addition to playing a key role in taste and smell, flavor molecules can also be involved in regulating metabolism and have an impact on health. In daily life, flavor molecules have absolute application value in food and spices. In scientific research, the study of flavor molecules is helpful to reveal the relationship between food intake and taste perception. Research on the combination behavior of flavor and food components can explore the retention, release and perception of flavor molecules. Most importantly, while exploring multi-sensory flavor perception, the food industry can fully mobilize the enthusiasm of researching new strategies for delicious and healthy food design.

Based on the FlavorDB database, collects and organizes 410 flavor molecules, which can be used in taste perception and other related studies.

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 24,293 mitophagy compounds, which can be used for drug development and mechanism research in cancer, immunity, infection and other hot research fields.

Macrocycles are promising scaffolds for the design of novel RNA targeting molecules. This collection of macrocycles for RNA consists of very diverse, drug-like molecules which incorporate certain known RNA-recognition elements (e.g. nucleobase ring systems and analogs) distributed within macrocyclic rings or peripheral fragments. As macrocyclic molecules tend to be larger than traditional screening molecules, it is vital to carefully assess and control their physicochemical properties. All macrocycles have been tested for aqueous and DMSO solubility with cutoffs applied at 10 mM in DMSO and 50 µM in PBS (pH 7.4); PAMPA permeability has also been tested for representative set of macrocycles.

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 5,484 Metabolism/Protease-related small molecules that act as a useful tool for drug discovery of metabolism-related diseases.

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 852 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.

Most of molecules enter or leave cells mainly via membrane transport proteins, which play important roles in several cellular functions, including cell metabolism, ion homeostasis, signal transduction, the recognition process in the immune system, energy transduction, etc. There are three major types of transport proteins, ATP-powered pumps, channel proteins and transporters. Transport proteins such as channels and transporters play important roles in the maintenance of intracellular homeostasis, and mutations in these transport protein genes have been identified in the pathogenesis of a number of hereditary diseases. In the central nervous system, ion channels have been linked to, but not limited to, many diseases such asataxias, paralyses, epilepsies, and deafness. This indicates the roles of ion channels in the initiation and coordination of movement, sensory perception, and encoding and processing of information. Ion channels are a major class of drug targets in drug development.

MCE designs a unique collection of 1,709 smal-molecule modulators that can be used for the research of Ion Channel and Membrane Transporter or high throughput screening (HTS) related drug discovery.

The MCE 1K Drug Fragment Library consists of 1,168 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).

PROTACs (Proteolysis-targeting chimeras) is a class of molecules that utilize ubiquitin-proteasome system (UPS) to ubiquitinate and degrade target proteins. The PROTACs molecule consists of two ligands joined by a linker. The one-to-one interaction between PROTACs and target proteins determines the high efficiency of PROTACs, making it a potential molecule for targeted protein degradation (TPD) therapy.

MCE supplies a unique collection of 340 PROTACs that effectively degrade target proteins with more powerful screening capability. MCE PROTAC Library is a useful tool for signal pathway research, protein degradation therapy research, drug discovery and drug repurposing, etc.

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 1,491 epigenetics-related compounds that can be used in the research of the related diseases.

Fragment-based drug development (FBDD) is a strategy for drug discovery that can be applied both academically and commercially to enhance the identification of some non-drug targets. Fragment-based drug development has identified low molecular weight molecules (<300 Da) capable of binding to related macromolecules. These fragments can cover a wide chemical space and are easy to optimize later. Currently, several fragment-based drugs have entered clinical trials, of which two drugs, Vemurafenib and Venetoclax, have been approved for marketing.

Based on Tanimoto coefficient, MCE uses similarity algorithm to carefully select 2,305 high-structurally diverse 'RO3' compliant fragment molecules from large-scale fragment molecules, which can be applied to fragment based drug development.

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.

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 752 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.

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 396 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.

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 1,757 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.

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 611 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.

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 483 small molecules related to extracellular vesicles (EVs). It is a good tool to be used for research on metabolize, cancer and other 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 2,699 RO5 drug-like natural products, which is an important tool for 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 1,450 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.

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 201 small allosteric modulators. It is a good tool to be used for research on metabolize, cancer and other diseases.

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 2,120 compounds targeting a variety of neurotransmitter receptors. MCE Neurotransmitter Receptor Compound Library is a useful tool for neurological diseases drug discovery.

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 1,347 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.

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 429 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.

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 2,505 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.

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 3,463 metabolic enzymes related small molecules, which is an important tool for studying the metabolic activities of organisms and developing drugs for metabolic diseases.

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 222 small molecules related to dopamine receptor. It is a good tool for screening drugs from nervous system disease.

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

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 1,048 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 5,738 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.

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-, VHL-, and DCAF-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 1200 molecular glue analogs, and these compounds serve as powerful tools for the research of molecular glues.

In the research of covalent inhibitors targeting serine and threonine, scientists have found that the nucleophilicity of these hydroxyl groups is significantly enhanced due to the influence of their surrounding environment. This results in higher activity during catalytic reactions. Aspirin, which targets the non-catalytic domain serine (Ser529 in human COX1) of cyclooxygenase, exerts its anti-inflammatory effect through covalent binding. β-lactam antibiotics, which targets the catalytic domain serine of penicillin-binding proteins, interferes with bacterial cell wall synthesis.

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 3,300 fragment molecules which can target serine and threonine residues and can be used for fragment-based covalent drug discovery.

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 65 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 2,300 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.

Lysine is the second most common target residue used in the design of TCIs and related covalent ligands. Its appeal lies in its abundance in human proteins, which is approximately three times higher than that of cysteine (5.8% vs. 1.9%). This significantly increases the number of proteins suitable for covalent targeting, especially given that many human proteins lack ligandable cysteine residues. Moreover, it has been suggested that functional lysines have a lower probability of being replaced by mutation, as they often play a crucial role in catalysis by acting as bases or nucleophiles. Additionally, lysines are essential for maintaining the structural integrity of proteins and for regulating post-translational modifications (PTMs). Consequently, targeting lysine has garnered significant interest in recent years.

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 445 fragment molecules which can target lysine residue and can be used for fragment-based covalent drug discovery.

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

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

MCE provides over 10,000 kinase fragment molecules that meet the above requirements and are available off the shelf, serving as an effective tool for screening and developing drugs targeting kinases.

Pesticide is a single substance or mixture that can be used to prevent, mitigate, iminate pests or as a plant conditioner, defoliant or desiccant. In recent years, scientists have proposed the concept of "Molecules to Ecosystems", bringing the concept of molecular biology to understand the impact of pesticides, degradation and relationship with the environment or organisms. MCE integrates effective compounds approved as pesticides by agencies such as the Environmental Protection Agency (EPA) and some insecticidal compounds with potential for agricultural applications.

MCE can provide a library of 293 pesticide compounds that are tool compounds for relevant research.