signaling molecule

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 2286 small molecules targeting GPCRs that can be used in the screening for various GPCRs-related research and drug development projects.

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 4627 compounds targeting a variety of membrane receptors. MCE Membrane reeptor-targeted Compound Library can be used for membrane receptor-focused screening and drug discovery.

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 352 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.

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

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 1436 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.

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 230 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.

Protein tyrosine kinases (PTKs) are key signaling molecules and important drug targets. Two classes of PTKs are present in cells: the transmembrane receptor PTKs (RTKs) and the nonreceptor PTKs. The RTK family includes the receptors for insulin and for many growth factors, such as EGFR, FGFR, PDGFR, VEGFR, and NGFR. RTKs are transmembrane glycoproteins that are activated by the binding of their ligands, and they transduce the extracellular signal to the cytoplasm by phosphorylating tyrosine residues on the receptors themselves (autophosphorylation) and on downstream signaling proteins. Their principal functions of PTKs involve the regulation of multicellular aspects of the organism. Cell to cell signals concerning growth, differentiation, adhesion, motility, and death are frequently transmitted through tyrosine kinases. In humans, tyrosine kinases have been demonstrated to play significant roles in the development of many disease states, including diabetes and cancers.

MCE designs a unique collection of 1055 compounds that act as a useful tool for PTKs-related drug screening and disease research.

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 18733 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.

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 6853 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 22835 compounds with confirmed biological activities and clear targets. These compounds include natural products, innovative compounds, approved compounds, and clinical compounds. This library is a useful tool for signal pathway research, drug discovery and drug repurposing, etc.

Bioactive Compound Library Plus, with more powerful screening capability, further complements Bioactive Compound Library (HY-L001) by adding some compounds with low solubility or solution stability (Part B) and some novel, rare or exclusive compounds (Part C) to this library. All those supplementary are supplied in powder form.

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 2048 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.

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 174 small allosteric modulators. 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 1118 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.

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 1392 smal-molecule modulators that can be used for the research of Ion Channel and Membrane Transporter or high throughput screening (HTS) related drug discovery.

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

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 3137 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.

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 1267 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 457 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.

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 890 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 1785 compounds targeting a variety of neurotransmitter receptors. MCE Neurotransmitter Receptor Compound Library is a useful tool for neurological diseases drug discovery.

Adult stem cells are important for tissue homeostasis and regeneration due to their ability to self-renew and generate multiple types of differentiated daughters. Self-renewal is reflected by their capacity to undergo multiple/limitless divisions. Several signaling pathways are involved in self-renewal of stem cells, that is, Notch, Wnt, and Hedgehog pathways or Polycomb family proteins. Recent studies mainly focus on cancer stem cell (CSCs), induced pluripotent stem cell (iPSCs), neural stem cell and maintenance of embryonic stem cell pluripotency. Among them, CSCs have been believed to be responsible for tumor initiation, growth, and recurrence that have implications for cancer therapy.

MCE owns a unique collection of 1740 compounds that can be used for stem cell regulatory and signaling pathway research.