Immune disorders

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 7,846 compounds that are useful tool for Immunology/Inflammation research or autoimmune inflammatory diseases drug discovery.

Amino acids are the fundamental components that sustain life activities, playing roles in ATP generation, promoting nucleotide synthesis, and maintaining cellular redox balance. Moreover, dysregulation of amino acid consumption is a significant potential regulatory mechanism leading to impaired anti-tumor immunity in immune cells. The normal functioning of immune cells relies on amino acid metabolic pathways to obtain energy and materials, and upon activation, they reprogram their metabolism to support growth, proliferation, and effector functions. Additionally, metabolic disorders of specific amino acids (such as branched-chain amino acids, glutamine, and arginine) can exacerbate mitochondrial dysfunction and oxidative stress, thereby promoting myocardial fibrosis and cardiac cell damage. Therefore, conducting research related to amino acid metabolism holds promise for discovering potential drugs for diseases related to cancer, immunity, and metabolism.

MCE can provide 198 kinds of metabolites of amino acid metabolic pathways, which can be used for drug screening in various diseases such as cancer, immune disorders, metabolic diseases, mitochondrial-targeted diseases

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 958 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.

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

The MCE lactic acid metabolite compound library contains 63 compounds and is constructed around key metabolic pathways involving lactate production, transport, and utilization. This library systematically includes core intermediates from glycolysis, the tricarboxylic acid (TCA) cycle, and the lactate cycle. Focusing on disease-associated metabolic reprogramming, it is suitable for research in oncology, inflammation, and metabolic disorders. The library can be used to elucidate the roles of lactate in tumor microenvironment regulation, immune evasion, and epigenetic modifications (such as protein lactylation). In addition, it provides high-quality small-molecule resources for drug screening, facilitating the discovery of potential modulators targeting key enzymes (such as LDH) or transporters (such as MCTs) involved in lactate metabolism.

The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is central to signaling by cytokine receptors, a superfamily of more than 30 transmembrane proteins that recognize specific cytokines, and is critical in blood formation and immune response. Canonical JAK/STAT signaling begins with the association of cytokines and their corresponding transmembrane receptors. Activated JAKs then phosphorylate latent STAT monomers, leading to dimerization, nuclear translocation, and DNA binding. In mammals, there are four JAKs (JAK1, JAK2, JAK3, TYK2) and seven STATs (STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, STAT6). Since the JAK/STAT pathway plays a major role in many fundamental processes, such as apoptosis and inflammation, dysfunctional proteins in the pathway may lead to a number of diseases. For example, alterations in JAK/STAT signalling can result in cancer and diseases affecting the immune system, such as severe combined immunodeficiency disorder (SCID).

MCE provides 704 compounds that can be used in the study of the JAK/STAT signaling pathway and related diseases.

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 163 inflammasomes related compounds. It is a good tool to be used for research on Inflammation, cancer and other diseases.

Pattern Recognition Receptors (PRRs) are a crucial class of protein molecules expressed in cells of the innate immune system. The core function of Pattern Recognition Receptors is to recognize Pathogen-Associated Molecular Patterns (PAMPs) and Damage-Associated Molecular Patterns (DAMPs). Upon recognizing and binding to PAMPs or DAMPs, PRRs rapidly initiate intracellular signaling pathways (such as the NF-κB, IRF, and inflammasome pathways). This triggers the production of inflammatory factors, chemokines, and type I interferons, thereby initiating inflammatory responses to eliminate pathogens or repair damage. PRRs represent the body's first line of defense against infection, and the rapidity and broad specificity of their response are crucial for host survival. However, aberrant activation of PRR signaling is also a cause of many chronic inflammatory diseases, autoimmune disorders, and neurodegenerative diseases. Therefore, precisely regulating PRR activity has become a key therapeutic strategy for these conditions.

MCE has cataloged 313 inhibitors targeting key PRRs, such as NLRs, TLRs, C-type Lectin Receptors (CLRs), and cGAS, to support drug discovery efforts for chronic inflammatory diseases.

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

Monomeric compounds derived from traditional Chinese medicines demonstrate excellent drug-like properties. They naturally possess structural diversity and clearly defined pharmacological activities, which help improve screening success rates and make them ideal tools for studying multi-target synergistic effects. This library contains 1,036 compounds, providing a material basis for investigating synergistic interactions among compounds (network pharmacology) and facilitating the development of multi-target therapeutic strategies for complex diseases such as cancer, neurodegenerative disorders, and metabolic syndrome.