activation system

Coagulation, also known as clotting, is the process in which blood changes from a liquid to a solid gel to form a blood clot. Thrombin, which is accurately and evenly generated in the injured part of blood vessels, is a key effector enzyme of the blood coagulation system and participates in many important biological processes, such as platelet activation, fibrinogen conversion to fibrin network, coagulation feedback amplification, etc. At the same time, to avoid the accidental formation of thrombus in the body, there is also an anticoagulant mechanism that inhibits blood coagulation.

Normal coagulation mechanism represents a balance between the pro-coagulant pathway in the injured site and anti-coagulant pathway beyond it. The blood coagulation system may be out of balance during the perioperative period or critical illness, which may lead to thrombosis or excessive bleeding. Therefore, the physiological study of coagulation balance is an important basis for clinical diagnosis and treatment of the abnormal coagulation process.

MCE supplies a unique collection of 965 compounds targeting key proteins in coagulation and anti-coagulation system. MCE Coagulation and Anti-coagulation Compound Library is a useful tool for study the mechanism of coagulation and anticoagulation.

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 1060 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.

GABA receptors are a class of receptors that respond to the neurotransmitter gamma-aminobutyric acid (GABA), the chief inhibitory neurotransmitter in the vertebrate central nervous system. There are two classes of GABA receptors: GABAA and GABAB. GABAA receptors are ligand-gated ion channels (also known as ionotropic receptors), whereas GABAB receptors are G protein-coupled receptors (also known asmetabotropic receptors). GABA receptors are significant drug targets in the treatment of neuropsychiatric disorders such as epilepsy, insomnia, and anxiety, as well as in anesthesia in surgical operations.

MCE offers a unique collection of 139 GABA receptors inhibitors and activators, which is an efficient tool for neuropsychiatric disorders drugs 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.

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

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

Chemokines, or chemotactic cytokines, are small cytokines or signaling proteins secreted by cells. They are a component of intercellular communication, controlling the directional movement of immune cells especially leukocytes, as well as other cell types, for instance, endothelial and epithelial cells, which are essential to maintain human health and the function of the immune system.

The biological effects of chemokines are achieved by binding to chemokine receptors, which are G protein-coupled receptors found on the surface of leukocytes. Some chemokine receptors are involved in directing tumor metastasis and over-expression by certain tumors. So inhibiting the interaction between chemokine and chemokine receptors on the surface of tumor cells may be a new possible therapeutic approach. Some chemokine receptors are coreceptors for HIV entry, and related inhibitors have been approved by the FDA to treat patients with HIV. Obviously, chemokines and chemokine receptors have become new targets for studying cancer, HIV, inflammation, and other diseases.

MCE supplies a unique collection of 146 chemokine or chemokine receptor inhibitors and activators, all of which have the identified inhibitory or activated effect on chemokine or chemokine receptors. MCE Chemokine Library is a useful tool for drug research related to cancer, AIDS, and wound therapy.

5-HT receptors, also called Serotonin receptors, are a group of G protein-coupled receptors (GPCRs) and ligand-gated ion channels (LGICs) found in the central and peripheral nervous systems. These receptors are now classified into seven families, 5-HT1–7, comprising a total of 14 structurally and pharmacologically distinct mammalian 5-HT receptor subtypes. The 5-HT receptors influence various biological and neurological processes such as aggression, anxiety, appetite, cognition, learning, memory, mood, nausea, sleep, andthermoregulation. The serotonin receptors are the target of a variety of pharmaceutical drugs, including many antidepressants, antipsychotics, anorectics, antiemetics, gastroprokinetic agents, antimigraine agents, hallucinogens, and entactogens.

MCE 5-HT Receptor Compound Library consists of 307 5-HT receptor inhibitors and activators, which can be used for neuropsychiatric disorders drugs discovery.

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 153 macrophage related compounds. It is a good tool to be used for research on Inflammation, 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.

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 1670 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.

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 2988 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.