tumor.

Cancer is a multi-step process which involves initiation, promotion and progression. Chemical carcinogens can alter any of these processes to induce their carcinogenic effects. People are continuously exposed exogenously to varying amounts of chemicals that have been shown to have carcinogenic or mutagenic properties in experimental systems. Exposure can occur exogenously when these agents are present in food, air or water, and also endogenously when they are products of metabolism or pathophysiologic states such as inflammation. The administration of chemical carcinogens is one of the most commonly used methods to induce tumors in several organs in laboratory animals in order to study oncologic diseases of humans. MCE offers a unique collection of 129 chemical carcinogens which have been identified with carcinogenic activity either in humans or in animal models. MCE Tumorigenesis-Related Compound Library is a powerful tool for studying oncologic diseases of humans. Standard opration based on safety data sheet will not cause harm to the body.

Animal disease models are used in a variety of settings in basic research, such as studies on mechanisms of disease progression and evaluation new drugs. Animal models can be broadly classified into five categories: 1) experimental, 2) spontaneous, 3) negative, 4) orphan, 5) genetically engineered. Experimental models, which are induced artificially in the laboratory, are most common. Some small molecular compounds are usually used as inducers for animal models, such as Ceruletide for inflammatory model, Azoxymethane for tumor model. These inducers are useful tool in building animal models.

MCE offers a unique collection of 50 animal model inducers, involving inflammatory model, tumor model, nervous disease model, etc. MCE Animal Disease Model library is a powerful tool for the establishment of animal disease models.

The blood-brain barrier (BBB) is the complex network of brain microvessels. It protects the brain from the external bloodstream environment and supplies the brain with the required nutrients for normal function. However, blood-brain barrier is also the obstacle to deliver beneficial drugs to treat CNS (central nervous system) diseases or brain tumors, as it has the least permeable capillaries in the entire body due to physical barriers (tight junctions). Therefore, it is crucial to discover drugs which can cross this barrier for the treatment of brain-based diseases, such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and epilepsy.

MCE offers a unique collection of 856 compounds with confirmed CNS-Penetrant property. It’s a useful tool for the discovery of drugs used for brain diseases, such as brain tumors, mental disorders, and neurodegenerative diseases.

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 486 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.

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 820 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.

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.

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 2116 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.

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.

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 7681 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.

With features of enormous scaffold diversity and structural complexity, natural products (NPs) are the main sources of lead compounds and new drugs and play a highly significant role in the drug discovery and development process, especially for cancer and infectious diseases. A large number of natural products have been proven to have potential anti-tumor effects, mainly from plants, animals, Marine organisms and microorganisms. At present, derived than 60% of anti-tumor drugs come from natural sources, and they are widely used in breast, prostate and colon cancers.

MCE offers a unique collection of 1582 natural products with validated anti-cancer activity. MCE anti-cancer natural product library is a useful tool for anti-tumor drugs screening and other related research.

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 2043 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.

Resistance refers to the decrease in the effectiveness of drugs in treating diseases or symptoms. Due to the increasing global antibiotic resistance, it may threaten our ability to treat common infectious diseases. Drug resistance is also the main cause of chemotherapy failure in malignant tumors. In approximately 50% of cases, drug resistance exists even before chemotherapy begins. There are many mechanisms of anticancer drug resistance, including increased protein expression that leads to drug removal, mutations in drug binding sites, recovery of tumor protein production, and pre-existing genetic heterogeneity in tumor cell populations. In addition, the issue of drug resistance seems to have affected the development of new anticancer drugs. Drug resistance may be caused by various conditions, such as mutations, epigenetic modifications, and upregulation of drug efflux protein expression. Overcoming multidrug resistance in cancer treatment is becoming increasingly important.

MCE designs a unique collection of 325 anti-drug-resistant compounds. It is a good tool to be used for research on cancer and other diseases.

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 1883 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.

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.

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 1788 radioprotectors. Radioprotector Library is an effective tool for acute Radiation Syndrome, drug combination research with radiation drugs.

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 100 chemotherapy drugs, which is a useful tool for cancer treatment research.

The PI3K/Akt/mTOR pathway controls many cellular processes that are important for the formation and progression of cancer, including apoptosis, transcription, translation, metabolism, angiogenesis, and cell cycle progression. Every major node of this signaling network is activated in a wide range of human tumors. Mechanisms for the pathway activation include activation of receptor tyrosine kinases (RTKs) upstream of PI3K, mutation or amplification of PIK3CA encoding p110α catalytic subunit of PI3K, mutation or loss of PTEN tumor suppressor gene, and mutation or amplification of Akt1. Once the pathway is activated, signaling through Akt can stimulate a series of substrates including mTOR which is involved in protein synthesis. Thus, inhibition of this pathway is an attractive concept for cancer prevention and/or therapy. Currently some mTOR inhibitors are approved for several indications, and there are several novel PI3K/Akt/mTOR inhibitors in clinical trials.

MCE owns a unique collection of 568 compounds that can be used for PI3K/Akt/mTOR pathway research. PI3K/Akt/mTOR Compound Library also acts as a useful tool for anti-cancer drug discovery.

Breast cancer is the most frequent cancer among women, impacting 2.1 million women each year, and also causes the greatest number of cancer-related deaths among women. Surgery is usually the first type of treatment for breast cancer, which is usually followed by chemotherapy or radiotherapy or, in some cases, hormone or targeted therapies, especially for metastatic breast cancer (MBC).

Breast cancer is a heterogeneous disease, which is categorized into 3 major subtypes based on the presence or absence of molecular markers for estrogen or progesterone receptors and human epidermal growth factor 2 (ERBB2; formerly HER2): hormone receptor positive/ERBB2 negative (70% of patients), ERBB2 positive (15%-20%), and triple-negative (tumors lacking all 3 standard molecular markers; 15%). Different intrinsic subtypes exhibit different tumor behavior with different prognoses, and may require specific targeted therapies to maximize treatment effectiveness. Otherwise, some signaling pathways also play important roles in the development of breast cancer, such as NF-κB Signaling Pathway, TGF-beta Signaling Pathway, PI3K/AKT/mTOR signaling pathway and Notch Signaling Pathway. These signaling pathways offer ideal targets for development of new targeted therapies for breast cancer.

MCE supplies a unique collection of 1953 compounds with identified and potential anti-breast cancer activity. MCE Anti-Breast Cancer Compound Library is a useful tool for anti-breast cancer drugs screening.

Nature has been a source of medicinal products for millennia, with many useful active substances developed from plant sources. In the 20th century, the discovery of the penicillin was the starting point for drug discovery from microbial sources. Microorganisms， which have been considered to be a rich source of unique bioactive compounds, play an important role in the development of the chemistry of natural products and medical therapy. Microbial metabolites have proved to be affective antimicrobial agents, anti-tumor agents, enzyme inhibitors, anti-inflammatory agents, etc. Today, many microbial-originated antibiotics are available in the mark, and a large number of bioactive metabolites are used in medicine.

MCE provides a unique collection of 573 microbial metabolites, which is an important source of lead compounds and can be used for drug discovery.

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.

Immunity refers to the ability of the body to resist the invasion of pathogenic microorganisms and resist a variety of diseases. Immunocompromised will inevitably lead to a series of diseases. Immunopotentiator are a class of compounds that enhance immune function and induce immune response. Immunopotentiator can activate the proliferation and differentiation of one or more kinds of immune active cells in the body, promote the secretion of lymphocytes, and then enhance the immune function of the body. Immunopotentiator are mainly used in the treatment of tumors, infectious diseases and immunodeficiency diseases. In addition, immunopotentiator are often used as adjuvants in combination with vaccine antigens to enhance the immunogenicity of vaccines.

MCE designs a unique collection of 80 compounds with definite or potential Immunopotentiating effect, mainly targeting the NOD-like Receptor (NLR), Toll-like Receptor (TLR), NF-κB, etc. It is an effective tool for development and research of anti-cancer, anti-infectious diseases and anti-immunodeficiency diseases compounds.

Cyclic peptides are polypeptide chains taking cyclic ring structure, which exhibit diverse biological activities, such as antibacterial activity, immunosuppressive activity and anti-tumor activity. Cyclic peptides, with the features of good binding affinity, target selectivity and low toxicity, show great success as therapeutics. Multiple cyclic peptides are currently in clinical use, for examples, gramicidin and tyrocidine with bactericidal activity, cyclosporin A with immunosuppressive activity, and vancomycin with antibacterial activity. Furthermore, cyclic peptides usually have the sufficient size and a balanced conformational flexibility/rigidity for binding to flat protein-protein interaction (PPI) interfaces, which have potential to develop PPI drugs.

MCE offers a unique collection of 84 cyclic peptides, all of which have good bioactivities. MCE Cyclic Peptide Library is a powerful tool for drug discovery and PPI inhibitor screening.

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.

Proteolysis-targeting chimera (PROTAC) has been developed to be a useful technology for targeted protein degradation. PROTACs consist of a ligand for E3 ligase (E3 ligase binder), a linker and a ligand (mostly small-molecule inhibitor) for protein of interest（target binder）. Upon binding to the target protein, the PROTACs can recruit E3 for target protein ubiquitination, which is subjected to proteasome-mediated degradation.

Although there are more than 600 E3 ubiquitin ligases, only several with small molecule ligands have been used for designing PROTACs, including Skp1-Cullin-F box complex containing Hrt1 (SCF), Von Hippel-Lindau tumor suppressor (VHL), Cereblon (CRBN), inhibitor of apoptosis proteins (IAPs), and mouse double minute 2 homolog (MDM2).

MCE carefully prepared a unique collection of 88 ligands for E3 ligase, which have been reported to be used in PROTAC design. MCE E3 ligase ligand library is a useful tool for PROTAC development.

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.

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 1816 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.

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 187 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.

Neuronal Signaling is involved in the regulation of the mechanisms of the central nervous system (CNS) such as its structure, function, genetics and physiology as well as how this can be applied to understand diseases of the nervous system. Every information processing system in the CNS is composed of neurons and glia, neurons have evolved unique capabilities for intracellular signaling (communication within the cell) and intercellular signaling (communication between cells). G protein-coupled receptors (GPCRs), including 5-HT receptor, histamine receptor, opioid receptor, etc. are the largest class of sensory proteins and are important therapeutic targets in Neuronal Signaling. Besides, Notch signaling, such as β- and γ-secretase, also plays multiple roles in the development of the CNS including regulating neural stem cell (NSC) proliferation, survival, self-renewal and differentiation. GPCR dysfunction caused by receptor mutations and environmental challenges contributes to many neurological diseases. Notch signaling in neurons, glia, and NSCs is also involved in pathological changes that occur in disorders such as stroke, Alzheimer's disease and CNS tumors. Thus, targeting Neuronal Signaling, such as notch signaling and GPCRs, can be used as therapeutic interventions for several different CNS disorders.

MCE designs a unique collection of 2542 Neuronal Signaling-related compounds that act as a useful tool for the research of neuronal regulation and neuronal 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 903 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.

Oxygen homeostasis regulation is the most fundamental cellular process for adjusting physiological oxygen variations, and its irregularity leads to various human diseases, including cancer. Hypoxia is closely associated with cancer development, and hypoxia/oxygen-sensing signaling plays critical roles in the modulation of cancer progression.

Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that functions as a master regulator of oxygen homeostasis. A variety of HF-1 target genes have been identified thus far which encode proteins that play key roles in critical developmental and physiological processes including angiogenesis/vascular remodeling, erythropoiesis, glucose transport, glycolysis, iron transport, and cell proliferation/survival.

HIF-1 is a heterodimeric transcription factor consisting of a constitutively expressed β-subunit and an oxygen-regulated α-subunit. The unique feature of HIF-1 is the regulation of HIF-1α expression and activity based upon the cellular O₂ concentration. Under normoxic conditions, hydroxylation of HIF-1α on these different proline residues is essential for HIF proteolytic degradation by promoting interaction with the von Hippel-Lindau tumor-suppressor protein (pVHL) through hydrogen bonding to the hydroxyproline-binding pocket in the pVHL β-domain. As oxygen levels decrease, hydroxylation of HIF decreases; HIF-1α then no longer binds pVHL, and becomes stabilized, allowing more of the protein to translocate to the cell’s nucleus, where it acts as a transcription factor, upregulating (often within minutes) the production of proteins that stimulate blood perfusion in tissues and thus tissue oxygenation.

MCE offers a unique collection of 2507 oxygen sensing related compounds targeting HIF/HIF Prolyl-Hydroxylase, MAPK/ERK, PI3K/AKT signaling pathways, etc. MCE Oxygen Sensing Compound Library is a useful tool to study hypoxia, oxidative stress and discover new anti-cancer drugs.