inflammatory proteins

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.

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 2,162 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.

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 1,670 small molecule compounds that can be used in the research of NF-κB signaling pathway or high throughput screening (HTS) related drug discovery.

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 2,383 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.

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.

Neuropeptides are small proteins produced and released by neurons through the regulation of secretory pathways, expressed in neurons and have transmitter or co-transmitter functions, and are used as nerve substrates. Neuropeptides are by far the largest and most diverse signaling molecules in the brain and have been implicated in the development of diseases and drugs. Neuropeptides are involved in inflammatory and immune diseases and have an impact on epithelial, vascular, and connective tissue cells proliferation and tissue repair. Studies have shown that neuropeptides are particularly important when the nervous system is challenged, such as stress, injury, or substance abuse. Substance P is a neuropeptide that acts as a neurotransmitter and neuromodulator in the central nervous system and is currently in clinical research and has been shown to be involved in inflammatory processes and pain.

MCE can provide 126 neuropeptides that can be used for scientific research.

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 1,885 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.

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 3,849 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.

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 1,332 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.

Kinases is a class of enzymes that adds chemicals called phosphates to other molecules, such as sugars or proteins. Protein phosphorylation serves as a critical regulatory mechanism for numerous cellular processes including cell division, metabolism, and signal transduction, with approximately 50% of cellular functions in humans being regulated by kinase activity. In drug discovery, kinases represent a major category of therapeutic targets, and kinase inhibitors constitute an important class of pharmaceuticals that block the activity of specific disease-associated enzymes, particularly in cancer and inflammatory disorders. Small molecule kinase inhibitors represent one of the fastest-growing drug categories, having received U.S. Food and Drug Administration (FDA) approval for both oncological and non-oncological indications. As of September 2023, over 70 FDA-approved small molecule kinase inhibitors are commercially available.

The MCE Kinase Inhibitor Library Mini contains 270 kinase inhibitors primarily targeting protein kinases (VEGFR, EGFR, BTK, CDK, Akt, etc.), lipid kinases (PI3K, PI4K, SK, etc.), and carbohydrate kinases. This collection includes 1-3 highly specific representative compounds per target, optimized for screening of kinase-related drug targets in pharmaceutical research.

Kinases are enzymes that catalyze the addition of phosphate groups to substrate molecules, a process known as phosphorylation. Protein phosphorylation serves as a critical regulatory mechanism for numerous cellular processes, including cell division, metabolism, and signal transduction. The human genome encodes over 500 kinases, which collectively regulate approximately 50% of cellular functions. Due to their pivotal roles, kinases represent one of the most important target classes in drug development.

Kinase inhibitors can selectively block the activity of disease-associated kinases, making them valuable therapeutics for conditions such as cancer and inflammatory diseases. FDA-approved kinase inhibitors have undergone extensive preclinical and clinical studies, demonstrating high bioactivity, favorable safety profiles, and good bioavailability, rendering them suitable for investigating new therapeutic indications.

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.

Heterocyclic compounds are cyclic organic compounds which contain at least one hetero atom, the most common heteroatoms are nitrogen, oxygen ,and sulfur. Heterocycles are common in biology, featuring a wide range of structures from enzyme co-factors to amino acids and proteins. On the one hand, heterocycles are common structural units in approved drugs and in medicinal chemistry targets in the drug discovery process. In addition, heterocycles have been found as a key structure in medical chemistry and also they are frequently found in large percent of biomolecules such as vitamins, natural products ,and biologically active compounds including antifungal, anti-inflammatory, antibacterial, antioxidant, antiallergic, anti-HIV, antidiabetic, anticancer activity.

MCE offers a unique collection of 6,484 heterocyclic compounds which can be used for drug discovery for high throughput screening (HTS) and high content screening (HCS). MCE heterocyclic compound library is critical for drug discovery and development.

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.

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 3,291 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.

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

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

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

MCE has assembled a collection of 5,860 known bioactive compounds and potential functional molecules, making this library suitable for a wide range of applications, including high-throughput drug screening, inhibitor identification, and mechanistic studies. It can be used to systematically evaluate the functional roles of lactylation in biological processes such as tumor metabolism, immune regulation, and inflammatory responses, and to efficiently identify small-molecule candidates with regulatory potential, thereby facilitating the development of innovative therapeutics targeting the interplay between metabolism and epigenetic regulation.