Inflammatory diseases.

Animal disease models are used in a variety of settings in basic research, such as studies on mechanisms of disease progression and evaluation new drugs. Animal models can be broadly classified into five categories: 1) experimental, 2) spontaneous, 3) negative, 4) orphan, 5) genetically engineered. Experimental models, which are induced artificially in the laboratory, are most common. Some small molecular compounds are usually used as inducers for animal models, such as Ceruletide for inflammatory model, Azoxymethane for tumor model. These inducers are useful tool in building animal models.

MCE offers a unique collection of 51 animal model inducers, involving inflammatory model, tumor model, nervous disease model, etc. MCE Animal Disease Model library is a powerful tool for the establishment of animal disease models.

Cytokines are a kind of low molecular soluble proteins synthesized and secreted by immunogen, mitogen or other factors. They have functions of regulating innate and adaptive immune responses, promoting hematopoiesis, stimulating cell activation, proliferation and differentiation. The process of releasing a large number of cytokines is also called “Cytokine storm”, which can cause damage to many tissues and organs in the body. Cytokine is involved in the pathogenesis of many human diseases, including cancer, diabetes, chronic inflammatory diseases and so on. Cytokine inhibitors are a class of essential compounds that act by directly inhibiting the synthesis and release of cytokine or blocking the binding of cytokine to their receptors. Cytokine inhibitors are important compounds for the study of tumor and autoimmune diseases.

MCE designs a unique collection of 997 cytokine inhibitors, mainly targeting the receptor interleukin (IL), colony-stimulating factor (CSF), interferon (IFN), tumor necrosis factor (TNF), growth factor (GF) and chemokine, which is an effective tool for development and research of anti-cancer, anti-chronic inflammatory diseases and anti-autoimmune diseases compounds.

Protein serine/threonine kinases (PSKs) are protein kinases that use ATP as a high-energy donor molecule to transfer phosphate groups to serine/threonine residues of target protein. As an important signal transduction regulator, serine/threonine kinases can affect the function of target proteins by disrupting enzyme activity or binding of target proteins to other proteins. Serine/threonine kinases are involved in the regulation of immune response, cell proliferation, differentiation, apoptosis and other physiological processes. Serine/threonine kinase inhibitors are an important class of compounds that have been widely studied in cancer, chronic inflammation, autoimmune diseases, aging and other diseases.

MCE designs a unique collection of 1,544 serine/threonine kinase inhibitors, mainly targeting the receptor PKA, Akt, PKC, MAPK/ERK, etc, which is an effective tool for development and research of anti-cancer, anti-chronic inflammatory diseases, anti-autoimmune diseases and anti-aging compounds.

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 632 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.

Inflammasomes are classic pattern recognition receptors for natural immune responses. Inflammasomes are polymeric protein complexes that regulate inflammatory responses and pyrolytic cell death, thereby exerting the host's defense against microorganisms. Inflammasomes sensors are associated with adapter proteins, activating inflammatory caspase-1, releasing inflammatory cytokines and inducing cell death, endowing the host with defense against pathogens. NLRP1, NLRP3, NLRC4, AIM2, and pyrin are considered typical inflammasomes because they convert cysteine asparaginase-1 into catalytically active capsaicin-1. In addition to infectious diseases, the importance of inflammasomes is also related to various clinical diseases, such as autoimmune diseases, neurodegeneration and metabolic disorders, and the development of cancer. Therefore, it is necessary to strictly regulate the activation and function of inflammasomes to avoid accidental host tissue damage while inducing pathogens to kill the inflammatory response.

MCE designs a unique collection of 99 inflammasomes related compounds. It is a good tool to be used for research on Inflammation, cancer and other diseases.

Cardiovascular diseases (CVDs) are a group of disorders of the heart and blood vessels which include coronary heart disease, cerebrovascular disease, peripheral arterial disease, rheumatic heart disease, etc. CVDs are the number 1 cause of death globally. Smoking, unhealthy nutrition, aging population, lack of physical activity, arterial hypertension, or diabetes can promote cardiovascular disease like myocardial infarction or stroke. It is multifactorial and encompasses a multitude of mechanisms, such as eNOS uncoupling, reactive oxygen species formation, chronic inflammatory disorders and abnormal calcium homeostasis. Antioxidant, anti-inflammatory and anti-diabetes agents may reduce the cardiovascular disease risk.

MCE supplies a unique collection of 1,871 compounds with confirmed anti-cardiovascular activity. These compounds mainly target metabolic enzyme, membrane transporter, ion channel, inflammation related signaling pathways. MCE Anti-Cardiovascular Disease Compound Library can be used for cardiovascular diseases related research and high throughput and high content screening for new drugs.

Inflammation promotes physiological and pathological processes by the activation of the immune system, local vascular system, and various cells within the damaged tissue. Accumulating epidemiological and clinical evidence shows that chronic inflammation is causally linked to various human diseases, including cerebrovascular, cardiovascular, joint, cutaneous, pulmonary, blood, liver, and intestinal diseases as well as diabetes.

Various natural products from Traditional Chinese Medicine (TCM) have been shown to safely suppress proinflammatory pathways and control inflammation-associated disease. MCE designs a unique collection of 1,228 Traditional Chinese Medicine active compounds with anti-inflammatory activity, which are derived from Coptis chinensis, Radix isatidis, Flos Lonicerae, Forsythia suspensa, etc. MCE Anti-inflammatory Traditional Chinese Medicine Active Compound Library is a useful tool for discovery anti-inflammatory drugs from TCM.

The immune system is a host defense system comprising many biological structures and processes within an organism that protects against disease. To function properly, an immune system must detect a wide variety of agents, known as pathogens, from viruses to parasitic worms, and distinguish them from the organism's own healthy tissue. Inflammation is also the body's attempt at self-protection to remove harmful stimuli and begin the healing process. It’s part of the body's immune response. The immune system recognizes damaged cells, irritants, and pathogens, and inflammation begins the healing process. Inflammatory abnormalities are a large group of disorders that underlie a vast variety of human diseases. The immune system is often involved with inflammatory disorders, demonstrated in both allergic reactions and some myopathies, with many immune system disorders resulting in abnormal inflammation.

MCE designs a unique collection of 6,258 compounds that are useful tool for Immunology/Inflammation research or autoimmune inflammatory diseases drug discovery.

Programmed cell death pathways, including apoptosis, pyroptosis and necroptosis, are regulated by unique sets of host proteins that coordinate a variety of biological outcomes. Pyroptosis is a highly inflammatory form of programmed cell death that occurs most frequently upon infection with intracellular pathogens and is likely to form part of the antimicrobial response. This process promotes the rapid clearance of various bacterial, viral, fungal and protozoan infections by removing intracellular replication niches and enhancing the host's defensive responses. Pyroptosis has been widely studied in inflammatory and infection disease models. Recently, there are growing evidences that pyroptosis also plays an important role in the development of cancer, cardiovascular diseases and Metabolic disorder, etc.

MCE designs a unique collection of 1,655 pyroptosis-related compounds mainly focusing on the key targets in the pyroptosis signaling pathway and can be used in the research of pyroptosis signal pathway and related diseases.

Accumulating evidence has revealed that intestinal microbiota play an important role in human health and disease, including cardiovascular diseases, inflammatory bowel disease, diabetes, obesity, cancer, and depression, etc. Changes in the composition of gut microbiota associated with disease, referred to as dysbiosis, have been linked to pathologies. Indeed, the gut microbiome functions like an endocrine organ, generating bioactive metabolites which play important roles in human metabolism, health, and disease. Gut microbiome has become a novel therapeutic target for many diseases. Analysis and identification of gut microbial metabolite will contribute to the development of therapeutic methods.

In order to meet the need of gut microbiome research, MCE carefully selected a unique collection of 512 gut microbial metabolites. MCE gut microbial metabolite library is a powerful tool for gut microbiome research and gut microbiome -related drug discovery.

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 1,105 small molecule compounds that can be used in the research of NF-κB signaling pathway or high throughput screening (HTS) related drug discovery.

Heat-clearing and detoxification is a specific treatment method in the research of traditional Chinese medicine (TCM), which is clinically used to treat infectious diseases with remarkable effect. Over the past decades, the research of heat-clearing and detoxification treatment has been one of the most active fields of combining traditional Chinese and western medicines, and has made remarkable achievements. Nowadays, the application field of heat-clearing and detoxification traditional Chinese medicine is not only limited to antibacterial and antiviral, but also has made progress in the research fields of anti-inflammatory reaction, anti-endotoxin, anti-peroxidative damage, anti-inflammatory cytokines, enhancement of immune function, protection of cellular organelles, and maintenance of calcium homeostasis. In addition to this, clearing heat and removing toxins has also made significant research progress in non-infectious diseases, for example, in tumors, cardiovascular diseases, renal diseases, blood diseases, geriatrics, and diabetes, all of which have shown good curative effect.

MCE can supply 1,327 monomer component from more than a hundred sources of heat-clearing and detoxification TCM, which can be used in TCM studies, drug development and mechanism-based studies.

Macrophages are effector cells of the innate immune system, engulfing bacteria and secreting pro-inflammatory and antibacterial mediators. They are an important component of the first line defense against pathogens and tumor cells. In addition, macrophages play an important role in eliminating damaged cells through programmed cell death. Like all immune cells, macrophages originate from pluripotent hematopoietic stem cells in the bone marrow. Macrophages play key functions in many physiological processes beyond homeostasis and innate immunity, including metabolic function, cell debris clearance, tissue repair, and remodeling. In order to fulfill their different functional roles, macrophages can polarize into a series of phenotypes, including classic (pro inflammatory, M1) and alternative (anti-inflammatory, healing promoting, M2) activation states, as well as a wide range of regulatory phenotypes and subtypes. Macrophages exist in all vertebrate tissues and have a dual function in host protection and tissue damage, maintaining a good balance.

MCE designs a unique collection of 195 macrophage related compounds. It is a good tool to be used for research on Inflammation, cancer and other diseases.

Transcription is the essential first step in the conversion of the genetic information in the DNA into protein and the major point at which gene expression is controlled. Transcription of protein-coding genes is accomplished by the multi-subunit enzyme RNA polymerase II and an ensemble of ancillary proteins, called transcription factors (TFs). Transcription factors play an important role in the long-term regulation of cell growth, differentiation and responses to environmental cues. Deregulated transcription factors contribute to the pathogenesis of a plethora of human diseases, ranging from diabetes, inflammatory disorders and cardiovascular disease to many cancers, and thus these proteins hold great therapeutic potential.

MCE offers a unique collection of 1,715 compounds with validated transcription factor targets modulating properties. MCE transcription factor-targeted compound library is an effective tool for researching transcription factors as drug targets as well as modulation of TFs for different therapeutic applications.

Flavonoids are an important class of natural products; particularly, they belong to a class of plant secondary metabolites having a polyphenolic structure, widely found in fruits, vegetables and certain beverages. Flavonoids can be subdivided into different subgroups depending on the carbon of the C ring on which the B ring is attached and the degree of unsaturation and oxidation of the C ring. These subgroups are: flavones, flavonols, flavanones, flavanonols, flavanols or catechins, anthocyanins and chalcones. Flavonoids are now considered as an indispensable component in a variety of nutraceutical, pharmaceutical, medicinal and cosmetic applications. This is attributed to their anti-oxidative, anti-inflammatory, anti-mutagenic and anti-carcinogenic properties coupled with their capacity to modulate key cellular enzyme function. Naturally occurring flavonoids are known to have biological activities for use as drugs, for example, in diseases like cancer, Alzheimer’s disease (AD), atherosclerosis, etc.

MCE offers a unique collection of 540 natural flavonoid compounds which is a useful tool for drug discovery as an important source of lead compounds.

Kinase is an enzyme that adds phosphate groups to other molecules. This process is known as phosphorylation. Protein phosphorylation is a key aspect in the regulation of a large number of cellular processes including cellular division, metabolism, signal transduction, and so on. There are over 500 kinases encoded by the human genome and it has been estimated that kinases regulate approximately 50% of cellular functions. Kinases are a large group of drug targets in drug discovery. Kinase inhibitors are an important class of drugs that block certain enzymes involved in diseases such as cancer and inflammatory disorders.

Kinase inhibitor library designed by MCE contains 3,157 kinase inhibitors and regulators mainly targeting protein kinases (VEGFR, EGFR, BTK, CDK, Akt, etc.), lipid kinases (PI3K, PI4K, SK, etc.) and carbohydrate kinases (Hexokinase), and is a useful tool for kinase drug discovery and related research.

Pain is a kind of distressing feeling caused by the stimulation of tissue damage. According to the International Association for the Study of Pain (IASP), pain is defined as ”An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage”.

Pain is usually classified according to its location, duration, underlying causes, and intensity. For example, acute and chronic pain, muscle pain, and nerve pain. Pain is the main symptom of most diseases, which seriously affects the quality of life and body function of patients. In the medical treatment of pain, anti-inflammatory drugs and opioid analgesic agents have traditionally been used, but the side effects are serious. In recent years, targeted drugs targeting the ERK/MAPK pathway or other targets have gradually become a research hotspot.

MCE supplies a unique collection of 2,425 compounds targeting key proteins in the pain system. MCE Pain-Related Compound Library is a useful tool for pain related research and anti-pain drug development.

DNA is prone to numerous forms of damage that can injure cells and impair fitness. Cells have developed an array of mechanisms to repair these injuries. Proliferating cells are especially vulnerable to DNA damage due to the added demands of cellular growth and division. Cell cycle checkpoints represent integral components of DNA repair that coordinate cooperation between the machinery of the cell cycle and several biochemical pathways that respond to damage and restore DNA structure. By delaying progression through the cell cycle, checkpoints provide more time for repair before the critical phases of DNA replication, when the genome is replicated, and of mitosis, when the genome is segregated. Loss or attenuation of checkpoint function may increase spontaneous and induced gene mutations and chromosomal aberrations by reducing the efficiency of DNA repair.

MCE owns a unique collection of 2,560 cell cycle/DNA damage-related compounds which can be used in the research of the same.