Activation-Induced Cell Death Inhibitors

Cell death plays a crucial role in the development of the body and the maintenance of internal balance to prevent the development of diseases. According to the regulation of the involved processes, cell death can be defined as programmed and non-programmed death. Programmed cell death (PCD) can be divided into lytic cell death and nonlytic cell death, mainly including apoptosis, necrotic apoptosis and Pyroptosis. Non-Programmed cell death (Non-PCD) generally refers to necrosis. In stark contrast to Accidental Cell Death (ACD), Regulatory Cell Death (RCD) relies on specialized molecular mechanisms. Cell death includes internal apoptosis, external apoptosis, necrotic apoptosis, ferroptosis, pyroptosis, lysosome-dependent cell death, etc.

MCE designs a unique collection of 2449 cell death compounds, covering multiple targets, such as Apoptosis, Ferroptosis, Pyroptosis, Necroptosis, etc. It is a useful tool for screening cell death drugs.

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 1723 compounds that can be used for stem cell regulatory and signaling pathway research.

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 1995 cell cycle/DNA damage-related compounds which can be used in the research of the same.

Ferroptosis is a novel type of cell death program that is distinct from apoptosis, necroptosis and autophagy. It is dependent on iron and reactive oxygen species (ROS) and is characterized by lipid peroxidation. As a novel type of cell death, ferroptosis has distinct properties and recognizing functions involved in physical conditions or various diseases including cancers, neurodegenerative diseases, acute renal failure, etc.

MCE carefully collected a unique collection of 922 ferroptosis signaling pathway related compounds with ferroptosis-inducing or -inhibitory activity. MCE Ferroptosis Compound Library is a useful tool to study ferroptosis mechanism as well as related diseases.

Normal mitochondrial function is critical for maintaining cellular homeostasis because mitochondria produce ATP and are the major intracellular source of free radicals. Cellular dysfunctions induced by intracellular or extracellular insults converge on mitochondria and induce a sudden increase in permeability on the inner mitochondrial membrane, the so-called mitochondrial membrane permeability transition (MMPT). MMPT is caused by the opening of pores in the inner mitochondrial membrane, matrix swelling, and outer membrane rupture. The MMPT is an endpoint to initiate cell death because the pore opening together with the release of mitochondrial cytochrome c activates the apoptotic pathway of caspases.

The normal operation of mitochondrial function is important for maintaining normal cell death and treatment of mitochondrial diseases. MCE offers a unique collection of 575 compounds with identified and potential mitochondrial protective activity. MCE Mitochondrial Protection Compound Library is critical for drug discovery and development.

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 1240 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.

Copper is an important co-factor of all biological enzymes, but if the concentration exceeds the threshold of maintaining the homeostasis mechanism, copper will lead to cytotoxicity. This death mechanism has been named "Cuproptosis".

The mechanism of cuproptosis distinct from all other known mechanisms of regulated cell death, including apoptosis, pyroptosis, necroptosis, and ferroptosis.

Copper combine with the lipoylated components of the tricarboxylic acid cycle (TCA), leading to lipoylated protein aggregation and subsequent loss of iron-sulfur cluster proteins, ultimately resulting in protein toxicity stress and cell death. Studies have shown that the necessary factors for cuproptosis include the presence of glutathione, mitochondrial metabolism of galactose and pyruvate, and glutamine metabolism.

Targeted regulation of cuproptosis is a potential choice to treat cancer, rheumatoid arthritis, and other diseases. For example, up-regulation of LIPT1 may inhibit the occurrence and development of tumors by destroying TCA in mitochondria and then inducing cuproptosis.

MCE supplies a unique collection of 188 cuproptosis-related compounds, all of which act on the targets or signaling pathways related to cuproptosis and may have in inhibitory or activated effect on cuproptosis. MCE Cuproptosis Library is a useful tool for drug research related to cancer, rheumatoid arthritis, and other 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 65 inflammasomes related compounds. It is a good tool to be used for research on Inflammation, cancer and other diseases.

Apoptosis is an ordered and orchestrated cellular process that occurs in physiological and pathological conditions, which is also called programmed cell death (PCD). Apoptosis plays a crucial role in developing and maintaining the health of the body by eliminating old cells, unhealthy cells and unnecessary cells. Too little or too much apoptosis contribute to many diseases. When apoptosis does not work correctly, cells that should be eliminated may persist and become immortal, for example, in cancer and leukemia. When apoptosis works overly well, it kills too many cells and inflicts grave tissue damage. This is the case in strokes and neurodegenerative disorders such as Alzheimer's, Huntington's, and Parkinson's disease.

MCE designs a unique collection of 2211 apoptosis-related compounds mainly focusing on the key targets in the apoptosis signaling pathway and can be used in the research of apoptosis signal pathway and related diseases.

Cancer is the second leading cause of death globally and seriously threatens human health. A neoplasm and malignant tumor are other common names for cancer. Disruption of the normal regulation of cell-cycle progression and division lies at the heart of the events leading to cancer. Target therapy, which targets proteins that control how cancer cells grow, divide and spread, plays an important role in cancer treatment. Recent studies mainly focus on targeting the key proteins for cancer surviving, cancer stem cells, the tumor microenvironment, tumor immunology, etc.

MCE designs a unique collection of 7677 anti-cancer compounds that target kinases, cell cycle key components, tumorigenesis related signaling pathways, etc. MCE Anti-cancer compound library is a useful tool for anti-cancer drug screening.

Radiotherapy is a common treatment for various cancers, and more than 50% of cancer patients require radiotherapy during the disease treatment. With advances in radiation technology and a better understanding of tumor biology, the efficacy of radiation therapy has gradually improved, and more and more patients have benefited from it. However, even with the use of advanced radiotherapy techniques, there are still many malignant tumor cells with low sensitivity to radiation, leading to the radiation effect is not ideal. To solve this problem, radiosensitizers have received more and more attention. Radiosensitizer is a kind of drug that can enhance the radiosensitivity of tumor cells and improve the effect of radiotherapy. Radiation sensitizers act in a variety of ways, such as killing hypoxic cells, enhancing DNA damage, inhibiting DNA damage repair, and blocking cell cycle progression, making tumor cells more susceptible to radiation damage and death than surrounding normal cells.

MCE designs a unique collection of 41 compounds with definite reported radiosensitization. It can be used for drug combination research in anti-cancer treatment.

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

Metabolism is the set of life-sustaining chemical reactions in organisms. Metabolic pathways are enzyme-mediated biochemical reactions that lead to biosynthesis (anabolism) or breakdown (catabolism) of natural product small molecules within a cell or tissue. Acting as catalysts, enzymes are crucial to metabolism - they allow a reaction to proceed more rapidly - and they also allow the regulation of the rate of a metabolic reaction. Proteases are used throughout an organism for various metabolic processes. Proteases control a great variety of physiological processes that are critical for life, including the immune response, cell cycle, cell death, wound healing, food digestion, and protein and organelle recycling. Imbalances in metabolic activities have been found to be critical in a number of pathologies, such as cardiovascular diseases, inflammation, cancer, and neurodegenerative diseases.

MCE designs a unique collection of 4515 Metabolism/Protease-related small molecules that act as a useful tool for drug discovery of metabolism-related diseases.

Extracellular vesicles (EVs) are small membrane binding structures that are released from cells into the surrounding environment and play a crucial role in mediating and regulating intercellular communication related to physiological and pathological processes. EVs are lipid membrane vesicles composed of proteins, lipids, and nucleic acids. EVs can be divided into several types based on their source, such as extracellular vesicles, microcapsules, and apoptotic vesicles. The size range of exosomes is 30-150nm, which are endocrine in multi vesicular endosomes (MVEs); microvesicles (50-1000nm) are secreted directly through extracellular interactions, thereby releasing plasma membrane vesicles. In contrast, apoptotic bodies are usually larger, ranging in size from 1 to 5 μ m. This is generated during programmed cell death. EV plays a crucial role in transmitting information between cells and influencing the behavior and function of receptor cells.

MCE designs a unique collection of 405 small molecules related to extracellular vesicles (EVs). It is a good tool to be used for research on metabolize, cancer and other diseases.

Aging is an unavoidable process, leading to cell senescence due to physiochemical changes in an organism. Aging cells cease to divide and drive the progression of illness through various pathways, resulting in the death of an organism ultimately. Anti-aging activities are primarily involved in the therapies of age-related disorders such as Parkinson's Disease (PD), Alzheimer's Disease (AD), cardiovascular diseases, cancer, and chronic obstructive pulmonary diseases.

Natural products are known as effective molecules in anti-aging treatments, which delay the aging process through influencing several pathways and thus ensure an extended lifespan. MCE offers a unique collection of 193 natural products with validated anti-aging activity. MCE anti-aging natural product library is a useful tool for the study of aging-related diseases drugs and pharmacology.

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 1045 compounds that act as a useful tool for PTKs-related drug screening and disease research.

Ovarian cancer is the most common cause of death in female genital malignancies, with the highest mortality rate in female genital malignancies. It is characterized by difficulty in detection in the early stage of the disease, high recurrence rate and poor prognosis. In fact, ovarian cancer includes many pathologic types. It is usually divided into epithelial ovarian cancer, malignant germ cell tumors and sex cord stromal tumors, of which epithelial ovarian cancer is the most dominant form. Clinical treatment of ovarian cancer prioritizes surgery combined with paclitaxel chemotherapy. However, due to the spread and drug resistance of tumor cells, the recurrence of ovarian cancer is high. In this case, combined with traditional methods, the development of new therapeutic agents can help to improve the treatment effect of ovarian cancer.

MCE designs a unique collection of 1867 compounds with definite or potential anti-ovarian cancer activity, which mainly targeting the main targets of ovarian cancer such as PARP, ATM/ATR, VEGFR and HIF/HIF Prolyl-Hydroxylase, etc. It is an essential tool for development and research of anti-ovarian compounds.

Lung cancer is a major global health problem, as it is the leading cause of cancer-related deaths worldwide. Lung cancer is divided into two categories: small cell lung cancer and non-small cell lung cancer (NSCLC). Non-small cell lung cancer accounts for about 85 percent of lung cancers.

As with all cancers, lung cancer may be treated with surgery, chemotherapy, radiation therapy, targeted therapy, immunotherapy or a combination thereof. Targeted therapy is one of the most exciting developments in lung cancer medicine, especially for NSCLC. Extensive genomic characterization of NSCLC has led to the identification of molecular subtypes of NSCLC that are oncogene addicted and exquisitely sensitive to targeted therapies. These include activating mutations in epidermal growth factor receptor (EGFR) and BRAF or echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusions and ROS1 receptor tyrosine kinase fusions. These are important targets for target therapy.

MCE offers a unique collection of 1823 compounds with identified and potential anti-lung cancer activity. These compounds target lung cancer’s major targets and signaling pathways. MCE anti-lung cancer compound library is a useful tool for anti-lung cancer drugs screening and other related research.

Cancer is the second leading cause of death worldwide and a serious threat to human health. Multiple treatments have been developed for cancer treatment, but new anti-cancer drugs still need to be developed urgently. Approved drugs, have well-characterized bioactivities, safety and bioavailability properties, will dramatically accelerate drug development.

MCE offers a unique collection of 1251 approved drugs with anti-cancer activity, which can be used for discovery of new anti-cancer drugs or as positive compounds used for anti-cancer research.

Endoplasmic reticulum (ER) contributes to the production and folding of approximately one third of cellular proteins, and is thus inextricably linked to the maintenance of cellular homeostasis and the fine balance between health and disease. However, some adverse factors negatively impact ER functions and protein synthesis, resulting in the activation of Endoplasmic reticulum stress (ER stress, ERS) and unfolded protein response (UPR) signaling pathways. The UPR is triggered when ER protein folding capacity is overwhelmed by cellular demand and the UPR initially aims to restore ER homeostasis and normal cellular functions. However, if this fails, then the UPR triggers cell death. Chronic ER stress and defects in UPR signaling are emerging as key contributors to a growing list of human diseases, including diabetes, neurodegeneration and cancer.

MCE Endoplasmic Reticulum Stress Compound Library contains 220 ER stress-related compounds that mainly target PERK, IRE1, ATF6, etc. MCE ER stress library is a useful tool for researching ER stress and related diseases.

Neurodegenerative diseases are incurable and life-threatening conditions that result in progressive degeneration and/or death of nerve cells. Some common neurodegenerative diseases include Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Motor Neuron Disease (MND), Huntington’s Disease (HD), Spino-Cerebellar Ataxia (SCA), Spinal Muscular Atrophy (SMA), and Amyotrophic Lateral Sclerosis (ALS). Because the pathophysiology of neurodegenerative disorders is generally poorly understood, it is difficult to identify promising molecular targets and validate them. At the same time, about 85% of the drugs fail in clinical trials. Therefore, validating new targets and discovering new drugs to mitigate neurodegenerative disorders is need of the hour.

MCE offers a unique collection of 2221 compounds with anti-Neurodegenerative Diseases activities or targeting the unique targets of neurodegenerative diseases. MCE Neurodegenerative Disease-related Compound Library is a useful tool for exploring the mechanism of neurodegenerative diseases and discovering new drugs for neurodegenerative diseases.

With the progress of modern cancer therapy, the life of cancer patients has been extended. However, after initial treatment and recovery, the development of secondary tumors often leads to cancer recurrence. Cancer stem cells are a small number of cells that tumor growth and reproduction depend on.

Cancer stem cells have strong self-renewal ability, which is the direct cause of tumor occurrence. In addition, cancer stem cells also have the ability to differentiate into different cell types, playing a crucial role in tumor metastasis and development. Chemotherapy and radiotherapy induced DNA damage and apoptosis are common cancer treatments. However, cancer stem cells can effectively protect cancer cells from apoptosis by activating DNA repair ability. Cancer stem cells are regarded as the key "seed" of tumor occurrence, development, metastasis and recurrence. Since its first discovery in leukemia in 1994, cancer stem cells have been considered a promising therapeutic target for cancer treatment.

MCE supplies a unique collection of 2090 compounds targeting key proteins in cancer stem cells. MCE Cancer Stem Cells Compound Library is a useful tool for cancer stem cells related research and anti-cancer drug development.

Chemotherapy is one of the most common treatments for cancer. It can be used alone for some types of cancer or in combination with other treatments such as radiation or surgery. Chemotherapy drugs usually target cells at different phases of the cell cycle and inhibit tumor proliferation and avoid cancer cell invasion and metastasis. It is a cancer treatment method that kills cancer cells with drugs.

Chemotherapeutic agents can be classified into alkylating agents, antimetabolites, antimicrotubular agents, antibiotics, etc. according to the mechanism of action. MCE offers a unique collection of 101 chemotherapy drugs, which is a useful tool for cancer treatment research.

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 349 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.

Mutations in oncogenes and tumor suppressor genes can modify multiple signaling pathways and in turn cell metabolism, which facilitates tumorigenesis. The paramount hallmark of tumor metabolism is “aerobic glycolysis” or the Warburg effect, coined by Otto Warburg in 1926, in which cancer cells produce most of energy from glycolysis pathway regardless of whether in aerobic or anaerobic condition. Usually, cancer cells are highly glycolytic (glucose addiction) and take up more glucose than do normal cells from outside. The increased uptake of glucose is facilitated by the overexpression of several isoforms of membrane glucose transporters (GLUTs). Likewise, the metabolic pathways of glutamine, amino acid and fat metabolism are also altered. Recent trends in anti-cancer drug discovery suggests that targeting the altered metabolic pathways of cancer cells result in energy crisis inside the cancer cells and can selectively inhibit cancer cell proliferation by delaying or suppressing tumor growth.

MCE provides a unique collection of 2029 compounds which cover various tumor metabolism-related signaling pathways. These compounds can be used for anti-cancer metabolism targets identification, validation as well anti-cancer 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 1418 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.

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 2038 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.

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 18820 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.

The majority of hypertensive patients have primary (or essential) hypertension, that is, hypertension in which secondary causes are not present. Management aims to control arterial pressure, prevent end-organ damage (cerebrovascular, cardiovascular, and renal), and reduce the risk of premature death.

Antihypertensive drugs may be divided into two broad groups, the first group being those which directly or indirectly block the renin–angiotensin system (RAS), for example, ACEIs, angiotensin receptor antagonists (ARAs), direct renin inhibitors (DRIs), and to a lesser extent β-blockers. The second group of drugs works by increasing water and sodium excretion, thereby reducing intravascular volume, or by causing vasodilatation through non-RAS pathways, for example, diuretics and calcium channel blockers (CCBs).

MCE offers a unique collection of 482 compounds with identified and potential antihypertensive activity. MCE Antihypertensive Compound Library is critical for antihypertensive drug discovery and development.

A parasite is an organism that lives on or in a host organism and gets its food from or at the expense of its host. Parasites of humans include protozoans, helminths, and ecto-parasites (organisms that live on the external surface of a host). They are responsible for many diseases and are transmitted to their hosts most often through the ingestion of contaminated food, water or through the bite of an arthropod (e.g., a fly or tick), which can act as an intermediate host and as a vector. Parasitic diseases of humans are a major global health problem causing significant morbidity and mortality, especially in developing countries. Each year there are hundreds of millions of people infected with disease-causing parasites, particularly in tropical and subtropical regions of the world, resulting in an estimated one million deaths. Therefore, there is a dire need of novel anti-parasitic drugs.

MCE has a unique collection of 451 compounds with validated anti-parasitic activity which offer researchers an opportunity to screen novel anti-parasitic targets.

Antibiotics are types of antimicrobial products used for the treatment and prevention of bacterial infections. Antibiotics can kill or inhibit bacterial growth. Although the target of an antibiotic is bacteria, some antibiotics also attack fungi and protozoans. However, antibiotics rarely have an effect on viruses. The major mechanism underlying antibiotics is the inhibition or regulation of enzymes involved in cell wall biosynthesis, nucleic acid metabolism and repair, protein synthesis, or disruption of membrane structure. Many of these cellular functions targeted by antibiotics are most active in multiplying cells. Since there is often overlap in these functions between prokaryotic bacterial cells and eukaryotic mammalian cells, it is not surprising that some antibiotics have also been found to be useful as anticancer agents.

MCE supplies a unique collection of 637 antibiotics, including penicillins, cephalosporins, tetracyclines, macrolides, etc. MCE Antibiotics Library is a useful tool for anti-bacterial or anti-cancer drugs discovery.

Radiation sickness is a general term for various types and degrees of damage (or disease) occurring in the human body after exposure to ionizing radiation. Although small amounts of ionizing radiation can also cause the body to produce free radicals and ROS, causing oxidative stress, resulting in DNA damage and chromosomal aberration. Radioprotector are compounds with radiation protection that can be used to prevent/protect non-tumor cells from the harmful effects of radiation. Radioprotective compounds can prevent the damage of radioactive substances to the human body and reduce the clinical symptoms of various radioactive diseases. In addition, radioprotectors can protect normal cells from damage during radiation therapy. The ideal anti-radiation drug should not affect the sensitivity of tumor cells to radiation therapy while protecting normal cells.

MCE designs a unique collection of 1785 radioprotectors. Radioprotector Library is an effective tool for acute Radiation Syndrome, drug combination research with radiation drugs.

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 4626 compounds targeting a variety of membrane receptors. MCE Membrane reeptor-targeted Compound Library can be used for membrane receptor-focused screening and drug discovery.

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 1395 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.

Alzheimer’s Disease (AD) is a progressive degenerative brain disease which causes mental and physical decline, gradually resulting in death. Despite the significant public health issue that it poses, only few medical treatments have been approved for Alzheimer’s Disease (AD) and these act to control symptoms rather than alter the course of the disease. Discovery of new therapeutic approaches depends on the study of pathology of AD. Recent research findings have led to greater understanding of disease neurobiology in Alzheimer's Disease (AD) and identification of unique targets for drug development. Several important mechanisms have been proposed to explain the underlying pathology of AD, such as Amyloid cascade hypothesis, Tau hypothesis and Cholinergic hypothesis, etc.

MCE offers a unique collection of 1366 compounds with anti-Alzheimer’s Disease activities or targeting the unique targets of AD. MCE Anti-Alzheimer’s Disease Compound Library is a useful tool for exploring the mechanism of AD and discovering new drugs for AD.

Neurodegenerative diseases are characterised by progressive dysfunction and death of neurons, such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis (MS). Neuroprotection is an approach to preserve neurons so that neurons cannot be hurt by different pathological factors in neurodegenerative diseases. Neuroprotectors are some agonists and antagonists targeting some key targets in neuroprotactive signal pathways, such as calcium and sodium channel blockers, GABA receptor agonists, NMDA receptor Antagonists, etc. Current neuroprotectors cannot reverse existing damage, but they may protect against further nerve damage and slow down any degeneration of the central nervous system (CNS) and still play important roles in the treatment of neurodegenerative diseases.

MCE offers a unique collection of 1051 compounds with potential neuroprotective activities. These compounds mainly act on some key targets in neuroprotetive signal pathways, such as calcium channel, sodium channel, adenosine A1 receptor, etc. MCE Neuroprotective Compopund Library is a useful tool in neuroprotective drug discovery.

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.

Immuno-Oncology is a type of immunotherapy that has the specific purpose of treating cancer. It works by stimulating our immune system to fight back. Normally, our immune system is able to destroy cancer cells in our body, however sometimes cancer cells can adapt and mutate, effectively hiding from our immune system. This is when tumors can develop and become a threat to our health. Immuno-oncology involves mobilizing lymphocytes to recognize and eliminate cancer cells using the body’s immune system. There are several immuno-oncology treatments available, including Immune cell therapy (CAR-T), monoclonal antibodies (mABs) and checkpoint inhibitors, cytokines and cancer vaccines.

MCE Small Molecule Immuno-Oncology Compound Library offers 484 bioactive tumor immunology compounds that target some important checkpoints such as PD1/PD-L1, CXCR, Sting, IDO, TLR, etc. This library is a useful tool for Immuno-oncology research.

Viruses are much simpler organisms than bacteria, and they are made from protein substances and nucleic acid. Despite the fact that the exact mechanism of infection is extremely specific to each type of virus, the general scheme of infection can be represented in the following manner: A virus is absorbed at the surface of a host cell and then permeates through the membrane, where it releases nucleic acid from its protein protection. Then the viral nucleic acid begins to replicate, and transcription of the viral genome takes place either in the cytoplasm, or in the nucleus of the host cell. As a result of these events, a large amount of viral nucleic acid and protein are made to make new generations of virions. Therefore, one mechanism of action of antiviral drugs is to interfere with the ability of a virus to get into a target cell. A second mechanism of action is to target the processes that synthesize virus components after a virus invades a cell, such as nucleotide or nucleoside analogs.

MCE designs a unique collection of 1275 anti-virus compounds that target several viruses, including SARS-CoV, HBV, HCV, HIV, HSV and Influenza Virus. It’s an effective tool for anti-virus drug discovery.

Blood cancers, also called hematologic cancers, occur when abnormal blood cells start growing out of control, interrupting the function of normal blood cells, which fight off infection and produce new blood cells. Most blood cancers start in the bone marrow, which is where blood is produced. There are three main types of blood cancers: leukemia, lymphoma and myeloma, which afflict millions of children and adults every year, and are often deadly.

Some common blood cancer treatments include stem cell transplantation, chemotherapy, radiation therapy, targeted therapy, immunotherapy or a combination thereof. As we begin to understand the key signaling pathways and molecular drivers of malignant transformation in haematological disorders, new treatment strategies will continue to be developed.

MCE offers a unique collection of 2657 compounds with identified and potential anti-blood cancer activity. These compounds target blood cancer’s major targets and signaling pathways. MCE anti-blood cancer compound library is a useful tool for anti-blood cancer drugs screening and other related research.

Protein phosphorylation is a key post-translational modification underlying the regulation of many cellular processes. Phosphatases and kinases contribute to the regulation of protein phosphorylation homeostasis in the cell. This reversible regulation of protein phosphorylation is critical for the proper control of a wide range of cellular activities, including cell cycle, proliferation and differentiation, metabolism, cell-cell interactions, etc.

Protein phosphatases have evolved in separate families that are structurally and mechanistically distinct. Based on substrate specificity and functional diversity, protein phosphatases are classified into two superfamilies: Protein serine/threonine phosphatases and Protein tyrosine phosphatases. Ser/Thr phosphatases are metalloenzymes belonging to two major gene families termed PPP (phosphoprotein phosphatase) and PPM (metal-dependent protein phosphatases), whereas protein tyrosine phosphatases (PTPs) belong to distinct classes of enzymes that utilize a phospho-cysteine enzyme intermediate as a part of their catalytic action.

MCE supplies a unique collection of 130 phosphatase inhibitors that mainly targeting protein tyrosine phosphatases (PTPs) and serine/threonine-specific protein phosphatases. MCE Phosphatase Inhibitor Library is a useful tool for phosphatase drug discovery and related 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 22628 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.

Exosomes are small membrane vesicles of endocytic origin that are secreted by most cells in culture. Exosomes contain nucleic acids, proteins, lipids, amino acids, and metabolites, etc. Their diverse constituents can reflect their cell of origin. Exosomes are associated with immune responses, viral pathogenicity, pregnancy, cardiovascular diseases, central nervous system-related diseases, and cancer progression. Proteins, metabolites, and nucleic acids delivered by exosomes into recipient cells effectively alter their biological response. Such exosome-mediated responses can be disease promoting or restraining.

The biology of exosomes in disease is still emerging, and the number of studies addressing their utility in the diagnosis and treatment of various pathologies has increased substantially. MCE supplies a unique collection of 45 compounds with the activity of inhibiting or stimulating exsomes secretion/biosynthesis. MCE Exosomes Compound Library is a useful tool for exsomes research.

Liver cancer is one of the leading malignancies which occupies the second position in cancer deaths worldwide, becoming serious threat to human health. Hepatocellular carcinoma (HCC), also known as hepatoma is the most common type accounting for approximately 90% of all liver cancers.

Current evidence indicates that during hepatocarcinogenesis, two main pathogenic mechanisms prevail: (1) cirrhosis associated with hepatic regeneration after tissue damage caused by hepatitis infection, toxins or metabolic influences, and (2) mutations occurring in single or multiple oncogenes or tumor suppressor genes. Both mechanisms have been linked with alterations in several important cellular signaling pathways. These include the RAF/MEK/ERK pathway, PI3K/AKT/mTOR pathway, WNT/b-catenin pathway, insulin-like growth factor pathway, c-MET/HGFR pathway , etc.

MCE offers a unique collection of 1798 compounds with identified and potential anti-liver cancer activity. MCE anti-liver cancer compound library is a useful tool for anti-liver cancer drugs screening and other related research.

Targeted cancer therapies are drugs or other substances that block the growth and spread of cancer by interfering with specific molecular targets that are involved in the growth, progression, and spread of cancer.

There are several different types of targeted therapy. The most common types are small-molecule drugs and monoclonal antibodies. Small-molecule drugs are small enough to enter cells easily, so they are used for targets that are inside cells, while monoclonal antibodies are usually used for targets that are located outside the cells. Because of high specificity, low side effect and potent anticancer activity, targeted therapy has become the mainstream of new anti-tumor drugs. Various targeted therapies have been approved by FDA and used in the treatment of diseases.

MCE carefully collects a unique of 107 targeted therapy drugs used in cancer treatment. MCE Targeted therapy drug library is a useful tool for the research of targeted therapy.

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 454 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.

Autophagy is a lysosomal degradation pathway that is essential for cell survival, differentiation, development, and homeostasis. The process of autophagy in mammalian cells is as follows: a portion of cytoplasm, including organelles, is enclosed by a phagophore or isolation membrane to form an autophagosome. The outer membrane of the autophagosome subsequently fuses with the endosome and then the lysosome, and the internal material is degraded. Autophagy plays a wide variety of physiological and pathophysiological roles. Defective autophagy contributes to various pathologies, including infections, cancer, neurodegeneration, aging, and heart disease.

MCE provides a unique collection of 1369 autophagy pathway-related compounds that is a useful tool for the research of autophagy-related regulation and diseases.

Glutamine is an important metabolic fuel that helps rapidly proliferating cells meet the increased demand for ATP, biosynthetic precursors, and reducing agents. Glutamine Metabolism pathway involves the initial deamination of glutamine by glutaminase(GLS), yielding glutamate and ammonia. Glutamate is converted to the TCA cycle intermediate α-ketoglutarate (α-KG) by either glutamate dehydrogenase (GDH) or by the alanine or aspartate transaminases (TAs), to produce both ATP and anabolic carbons for the synthesis of amino acids, nucleotides and lipids. During periods of hypoxia or mitochondrial dysfunction, α-KG can be converted to citrate in a reductive carboxylation reaction catalyzed by IDH2. The newly formed citrate exits the mitochondria where it is used to synthesize fatty acids and amino acids and produce the reducing agent, NADPH.

Cancer cells display an altered metabolic circuitry that is directly regulated by oncogenic mutations and loss of tumor suppressors. Mounting evidence indicates that altered glutamine metabolism in cancer cells has critical roles in supporting macromolecule biosynthesis, regulating signaling pathways, and maintaining redox homeostasis, all of which contribute to cancer cell proliferation and survival. Thus, intervention in glutamine metabolic processes could provide novel approaches to improve cancer treatment.

MCE owns a unique collection of 898 compounds targeting the mainly proteins and enzymes involved in glutamine metabolism pathway. Glutamine Metabolism compound library is a useful tool for intervention in glutamine metabolic processes.

The endocrine system is a chemical messenger system comprising feedback loops of the hormones released by internal glands of an organism directly into the circulatory system, regulating distant target organs. Hormones are chemicals that serve to communicate between organs and tissues for physiological regulation and behavioral activities. Hormones affect distant cells by binding to specific receptor proteins in the target cell, resulting in a change in cell function.

The endocrine system is concerned with the integration of developmental events proliferation, growth, and differentiation, and the psychological or behavioral activities of metabolism, growth and development, tissue function, sleep, digestion, respiration, excretion, mood, stress, lactation, movement, reproduction, and sensory perception caused by hormones. Irregulated hormone release, inappropriate response to signaling or lack of a gland can lead to endocrine disease.

MCE offers a unique collection of 883 endocrinology related compounds targeting varieties of hormone receptors such as thyroid hormone receptor, TSH receptor, GNRH receptor, adrenergic receptor, etc. MCE Endocrinology Compound Library is a useful tool for the discovery of endocrinology drugs.

Metabolism is the set of life-sustaining chemical reactions in organisms that maintain cell homeostasis. Metabolic pathways are enzyme-mediated biochemical reactions that lead to biosynthesis (anabolism) or breakdown (catabolism) of molecules including glucose metabolism, lipid metabolism and amino acid or protein metabolism within a cell or tissue. As catalysts, enzymes are crucial to metabolism as they allow a reaction to proceed more rapidly and tregulate the rate of a metabolic reaction. Due to the importance of metabolic balance in the organism, the abnormal function of metabolic enzymes often leads to the occurrence of a variety of metabolic diseases, such as diabetes, obesity, cardiovascular disease, etc.

MCE designs a unique collection of 2825 metabolic enzymes related small molecules, which is an important tool for studying the metabolic activities of organisms and developing drugs for metabolic diseases.