| Anticancer

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 1,436 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.

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 8,510 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 1,706 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 2,227 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.

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

Glycolysis is a series of metabolic processes by which one molecule of glucose is catabolized to two molecules of pyruvate with a net gain of two ATP. Glycolysis takes place in 10 steps and catalyzed by a series of enzyme, such as hexokinase, Glucose-6-phosphate isomerase, Phosphofructokinase, etc. Glycolysis is used by all cells in the body for energy generation.

Most cancer cells exhibit increased glycolysis and use this metabolic pathway for generation of ATP as a main source of their energy supply. This phenomenon is known as the Warburg effect and is considered as one of the most fundamental metabolic alterations during malignant transformation. Because increased aerobic glycolysis is commonly seen in a wide spectrum of human cancers, development of novel glycolytic inhibitors as a new class of anticancer agents is likely to have broad therapeutic applications.

MCE provides a unique collection of 740 glycolysis compounds that mainly target hexokinase, glucokinase, enolase, pyruvate kinase, PDHK, etc. MCE Glycolysis Compound Library is a useful tool for glucose metabolism research and anti-cancer drug discovery.

New drug development is a time-consuming and high-cost process. Drug repurposing (also called drug repositioning, reprofiling or re‑tasking) offers various advantages over developing an entirely new drug for a given indication, such as lower risk and less investment. Clinical drugs have confirmed bioactivities, clear mechanisms and high safety that are suitable for drug repurposing.

MCE owns a unique collection of 2,588 clinical compounds that refer to various research areas including anti-cancer, anti-infection, anti-inflammation, nervous disease. Those compounds are of detailed information on clinical development status, research area, targets, etc.

The TCA cycle (tricarboxylic acid cycle)—is also known as the Krebs cycle or the citric acid cycle (CAC). The TCA cycle is a series of chemical reactions that release stored energy through the oxidation of acetyl-CoA in carbohydrates, fats, and proteins.

For decades, the TCA cycle has been considered as the central pathway for cell oxidative phosphorylation to produce energy and biosynthesis. Research shows that TCA cycle is associated with many diseases, especially cancer. In colon carcinoma, liver cancer and other cancers, there are mutations that lead to the imbalance of TCA cycle metabolites, indicating that TCA cycle may be related to the occurrence of cancer. Understanding the role and molecular mechanism of TCA cycle in inhibiting or promoting cancer progression will promote the development of new metabolite-based cancer treatment methods in the future.

MCE supplies a unique collection of 66 compounds related to the TCA cycle. MCE TCA Cycle Compound Library is a useful tool for the TCA cycle related research and anti-cancer drug development.

New drug development is a time-consuming and high-cost process. Drug repurposing (also called drug repositioning, reprofiling or re‑tasking) offers various advantages over developing an entirely new drug for a given indication, such as lower risk and less investment. Clinical drugs have confirmed bioactivities, clear mechanisms and high safety that are suitable for drug repurposing.

MCE owns a unique collection of 3,201 clinical compounds that refer to various research areas including anti-cancer, anti-infection, anti-inflammation, nervous disease. Those compounds are of detailed information on clinical development status, research area, targets, etc. Clinical Compound Library Plus, with powerful screening capability, further complements Clinical Compound Library (HY-L026) by adding some compounds with low solubility or solution stability (Part B) to this library. All those supplementary are supplied in powder form.

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.

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 94 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.

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 2,296 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.

Protein serine/threonine kinases (PSKs) are protein kinases that use ATP as a high-energy donor molecule to transfer phosphate groups to serine/threonine residues of target protein. As an important signal transduction regulator, serine/threonine kinases can affect the function of target proteins by disrupting enzyme activity or binding of target proteins to other proteins. Serine/threonine kinases are involved in the regulation of immune response, cell proliferation, differentiation, apoptosis and other physiological processes. Serine/threonine kinase inhibitors are an important class of compounds that have been widely studied in cancer, chronic inflammation, autoimmune diseases, aging and other diseases.

MCE designs a unique collection of 1,371 serine/threonine kinase inhibitors, mainly targeting the receptor PKA, Akt, PKC, MAPK/ERK, etc, which is an effective tool for development and research of anti-cancer, anti-chronic inflammatory diseases, anti-autoimmune diseases and anti-aging compounds.

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 891 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.

Glycosides are compounds in which a sugar group is bonded through its anomeric carbon to another group via a glycosidic bond. Many biologically active compounds are glycosides. Glycosides comprise several important classes of compounds such as hormones, sweeteners, alkaloids, flavonoids, antibiotics, etc. The glycosidic residue can be crucial for their activity or can only improve pharmacokinetic parameters. Glycosides, which exhibit anti-inflammatory, anti-infection, anti-cancer and anti-oxidative properties, play numerous important roles in living organisms, such as streptomycin, as an aminoglycoside antibiotic, has anti-infection activity. Anthracyclines possess good antibacterial and anti-cancer activities.

MCE Glycoside Compound Library contains a unique collection of 806 glycoside compounds and is a useful tool to discovery glycoside drugs.

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 435 anti-drug-resistant compounds. It is a good tool to be used for research on cancer and other diseases.

Mitochondria, as the main place of energy supply in life, is essential to maintain normal life activities. Mitochondrial dysfunction is associated with common diseases, such as cardiovascular diseases, neurodegenerative diseases, diabetes and cancer. The heart, brain and liver rely heavily on mitochondrial function as the main organs for drug metabolism. In addition, mitochondria is also a target of many drugs, some of which induce organotoxicity by inducing mitochondrial toxicity.

MCE contains 486 mitochondrial toxic compounds, which can be used as tool compounds for drug development and disease mechanism research.

Drug-induced liver injury (DILI; also known as drug-induced hepatotoxicity) is caused by medications (prescription or OTC), herbal and dietary supplements (HDS), or other xenobiotics that result in abnormalities in liver tests or in hepatic dysfunction that cannot be explained by other causes. Drugs are an important cause of liver injury. Drug-induced hepatic injury is the most common reason cited for withdrawal of an approved drug.

DILI is thought to occur via several different mechanisms. Among these are direct impairment of the structural (e.g., mitochondrial dysfunction) and functional integrity of the liver; production of a metabolite that alters hepatocellular structure and function; production of a reactive drug metabolite that binds to hepatic proteins to produce new antigenic drug-protein adducts, which are targeted by hosts’ defenses (the hapten hypothesis); and initiation of a systemic hypersensitivity response (i.e., drug allergy) that damages the liver.

MCE Drug-induced Liver Injury (DILI) Compound Library contains a unique collection of 1,434 hepatotoxicity causing compounds and is a powerful tool to research DILI and other drug toxicities. This library can be used to understand the mechanisms of DILI, identify biomarkers for early DILI prediction, and allow timely recognition during drug development, thus finally achieving successful DILI prevention and assessment in the pre-marketing phase.

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 999 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.

A protease (also called a peptidase, proteinase, or proteolytic enzyme) is an enzyme that catalyzes proteolysis, breaking down proteins into smaller polypeptides or single amino acids, and spurring the formation of new protein products. Proteases play important roles in regulating multiple biological processes in all living organisms, such as regulating the fate, localization, and activity of many proteins, modulating protein-protein interactions, creating new bioactive molecules, contributing to the processing of cellular information, and generating, transducing, and amplifying molecular signals.

Proteases are important targets in drug discovery. Some protease inhibitors are often used as anti-virus drugs and anti-cancer drugs. MCE offers a unique collection of 617 protease inhibitors. MCE Protease Inhibitor Library is critical for drug discovery and development.

Boric acid is a stable and usually non-toxic group widely used in modern synthesis to form C-C and C-heteroatom bonds. Boric acid exhibits exquisite reversible coordination characteristics and can be explored as a molecular construction tool, with specific mechanisms for controlling the structure and biological characteristics of bioconjugates. Boric acid has various activities, such as anticancer, antibacterial, and antiviral activities. In drugs, boric acid mainly exists in the form of arylboronic acid. In addition to this form, heterocycles containing boric acid, such as pyridine, pyrrole, and indole derivatives, are also very useful in pharmaceutical chemistry. Molecular modification by introducing boric acid groups into bioactive molecules has been shown to alter selectivity, physicochemical, and pharmacokinetic characteristics, and improve existing activity.

MCE designs a unique collection of 128 boronic acid compounds. It is a good tool to be used for research on cancer and other diseases.

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.

Alkaloids are a large and complex group of cyclic compounds that contain N. About 2,000 different alkaloids have been isolated. Important alkaloids include morphine, strychnine, atropine, colchicine, ephedrine, quinine, and nicotine. Alkaloids are useful as diet ingredients, supplements, and pharmaceuticals, in medicine and in other applications in human life. They showed anti-inflammatory, anticancer, analgesics, local anesthetic and pain relief, neuropharmacologic, antimicrobial, antifungal, and many other activities. Alkaloids are also important compounds in organic synthesis for searching new semisynthetic and synthetic compounds with possibly better biological activity than parent compounds.

MCE designs a unique collection of 547 alkaloids that all come from natural products. MCE Alkaloids Library is a useful tool for drug discovery that can be used for high throughput screening (HTS) and high content screening (HCS).

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

MCE offers a unique collection of 6,133 heterocyclic compounds which can be used for drug discovery for high throughput screening (HTS) and high content screening (HCS). MCE heterocyclic compound library is critical for drug discovery and development.

Nucleoside and nucleotide analogues are synthetic, chemically modified compounds that have been developed to mimic their physiological counterparts in order to exploit cellular metabolism and subsequently be incorporated into DNA and RNA to inhibit cellular division and viral replication. In addition to their incorporation into nucleic acids, nucleoside and nucleotide analogues can interact with and inhibit essential enzymes such as human and viral polymerases (that is, DNA-dependent DNA polymerases, RNA-dependent DNA polymerases or RNA-dependent RNA polymerases), kinases, ribonucleotide reductase, DNA methyltransferases, purine and pyrimidine nucleoside phosphorylase and thymidylate synthase. These actions of nucleoside and nucleotide analogues have potential therapeutic benefits — for example, in the inhibition of cancer cell growth, the inhibition of viral replication as well as other indications.

MCE offers a unique collection of 539 nucleotide compounds including nucleotide, nucleoside and their structural analogues. MCE Nucleotide Compound Library is a useful tool to discover anti-cancer and antiviral drugs for high throughput screening (HTS) and high content screening (HCS).

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 390 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.

Oceans cover more than 70% of the Earth’s surface and host a huge species diversity. Marine organisms are considered the most recent source of bioactive natural products after terrestrial plants and nonmarine microorganisms. Marine biological sources are taxonomically diverse and include sponges, tunicates, corals, mollusks, fungi, and sediment-derived bacteria.

Marine organisms can produce a plethora of small molecules with novel chemical structures and potent biological properties, being a rich source for the discovery of pharmacologically active compounds, already with several marine-derived agents approved as drugs. Ziconotide, a peptide originally discovered in a tropical cone snail, was the first marine-derived compound to be approved in the United States in December 2004 for the treatment of pain. Then, in October 2007, Trabectedin became the first marine anticancer drug to be approved in the European Union.

MCE offers a unique collection of 45 marine-sourced natural products which can be used for drug discovery for high throughput screening (HTS) and high content screening (HCS). MCE marine-sourced natural product library is an important source for drug discovery and development.

Chinese herbal therapy is an important part of Traditional Chinese Medicine (TCM). It has been used for centuries in China, where herbs are considered fundamental therapy for many acute and chronic conditions. Many studies indicated TCM exerted an overall regulatory effect via multi-component and multi-target network. Active components from Traditional Chinese Medicine possess many medicinal properties such as antioxidant, anti-cancer, and anti-bacterial effects, which makes it an important source of new drugs. Nearly 200 modern medicines have been developed either directly or indirectly from the plants used as medicines in China. For example, artemisinin, used in multidrug resistant malaria, was first isolated from the Chinese herb Artemisia annua L. Today, scientists continue to identify compounds in Chinese herbal remedies that may be useful in the development of new therapeutic agents applicable in Western medicine.

MCE designs a unique collection of 2,924 active compounds of Chinese Herbal Medicines. MCE Traditional Chinese Medicine Active Compound Library is a useful tool for discovery new drugs from TCM.

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 616 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.

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 2,742 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.