human cancers

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 1247 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 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.

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.

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.

The developmental proteins Hedgehog, Notch and Wnt are key regulators of cell fate, proliferation, migration and differentiation in several tissues. Their related signaling pathways are frequently activated in tumors, and particularly in the rare subpopulation of cancer stem cells. The Wnt signaling pathway is a conserved pathway in animals. Deregulated Wnt signaling has catastrophic consequences for the developing embryo and it is now well appreciated that defective Wnt signaling is a causative factor for a number of pleiotropic human pathologies, including cancer. Hedgehog signaling pathway is linked to tumorigenesis and is aberrantly activated in a variety of cancers. The Notch signaling pathway is a highly conserved cell signaling system present in most animals. It plays an important role in cell-cell communication, and further regulates embryonic development.

MCE designs a unique collection of 352 Wnt/Hedgehog/Notch signaling pathway-related small molecules. Wnt/Hedgehog/Notch Compound Library serves as a useful tool for stem cell research and anti-cancer drug screening.

Nuclear receptors (NR) are proteins found in cells that sense androgen and thyroid hormones and certain other molecules. They are ligand-activated transcription factors that participate in many aspects of human physiology and pathology, and regulate the expression of various important genes.

Nuclear receptors have become one of the main targets in the development of new drug strategies, providing a unique type of receptors for studying a variety of human diseases, such as breast cancers, skin disorders and diabetes. 13% of U.S. Food and Drug Administration (FDA) approved drugs target nuclear receptors.

MCE supplies a unique collection of 661 nuclear receptor inhibitors and activators, all of which have the identified inhibitory or activated effect on nuclear receptor. MCE Nuclear Receptor Library is a useful tool for drugs research related to cancer, skin disease and diabetes.

Human metabolism is an integral part of cellular function that reflects individual differences in health, disease, diet, and lifestyle. Many health conditions such as obesity, diabetes, hypertension, heart disease, and cancer are associated with abnormal metabolic states. In the pathological state of the human body, metabolic pathways are significantly altered, resulting in aberrant levels of intermediates or end-products that can be viewed as potential diagnostic biomarkers or even therapeutic targets. Therefore, detection, identification and quantification of human metabolites are very important for drug metabolism research in drug development.

MCE offers a unique collection of 5945 human metabolites, including endogenous metabolites and exogenous metabolites, covering multiple structure types, such as lipids, amino acids, nucleic acids, carbohydrates, organic acids, biogenic amines, vitamins,. MCE Human Metabolites Library is a helpful tool for studying the relationship between diseases and metabolism.

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 689 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.

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.

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.

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 491 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).

Accumulating evidence has revealed that intestinal microbiota play an important role in human health and disease, including cardiovascular diseases, inflammatory bowel disease, diabetes, obesity, cancer, and depression, etc. Changes in the composition of gut microbiota associated with disease, referred to as dysbiosis, have been linked to pathologies. Indeed, the gut microbiome functions like an endocrine organ, generating bioactive metabolites which play important roles in human metabolism, health, and disease. Gut microbiome has become a novel therapeutic target for many diseases. Analysis and identification of gut microbial metabolite will contribute to the development of therapeutic methods.

In order to meet the need of gut microbiome research, MCE carefully selected a unique collection of 500 gut microbial metabolites. MCE gut microbial metabolite library is a powerful tool for gut microbiome research and gut microbiome -related drug discovery.

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.

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.

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.

Transcription is the essential first step in the conversion of the genetic information in the DNA into protein and the major point at which gene expression is controlled. Transcription of protein-coding genes is accomplished by the multi-subunit enzyme RNA polymerase II and an ensemble of ancillary proteins, called transcription factors (TFs). Transcription factors play an important role in the long-term regulation of cell growth, differentiation and responses to environmental cues. Deregulated transcription factors contribute to the pathogenesis of a plethora of human diseases, ranging from diabetes, inflammatory disorders and cardiovascular disease to many cancers, and thus these proteins hold great therapeutic potential.

MCE offers a unique collection of 1288 compounds with validated transcription factor targets modulating properties. MCE transcription factor-targeted compound library is an effective tool for researching transcription factors as drug targets as well as modulation of TFs for different therapeutic applications.

Kinase is an enzyme that adds phosphate groups to other molecules. This process is known as phosphorylation. Protein phosphorylation is a key aspect in the regulation of a large number of cellular processes including cellular division, metabolism, signal transduction, and so on. There are over 500 kinases encoded by the human genome and it has been estimated that kinases regulate approximately 50% of cellular functions. Kinases are a large group of drug targets in drug discovery. Kinase inhibitors are an important class of drugs that block certain enzymes involved in diseases such as cancer and inflammatory disorders.

Kinase inhibitor library designed by MCE contains 3137 kinase inhibitors and regulators mainly targeting protein kinases (VEGFR, EGFR, BTK, CDK, Akt, etc.), lipid kinases (PI3K, PI4K, SK, etc.) and carbohydrate kinases (Hexokinase), and is a useful tool for kinase drug discovery and related research.

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

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

MAPK families play an important role in complex cellular programs like proliferation, differentiation, development, transformation, and apoptosis. In mammalian cells, four MAPK families have been clearly characterized: ERK1/2, C-Jun N-terminal kinse/stress-activated protein kinase (JNK/SAPK) , p38 kinase and ERK5. They respond to different signals. Each MAPK-related cascade consists of three enzymes that are activated in series: a MAPK kinase kinase (MAPKKK), a MAPK kinase (MAPKK) and a MAP kinase (MAPK). MAPK signaling pathways has been implicated in the development of many human diseases including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and various types of cancers.

MCE designs a unique collection of 510 MAPK signaling pathway inhibitors that act as a useful tool for MAPK-related drug screening and disease 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 219 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.

The transforming growth factor beta (TGF-β) signaling pathway is involved in many cellular processes in both the adult organism and the developing embryo including cell growth, cell differentiation, apoptosis, cellular homeostasis and other cellular functions. The TGF-β superfamily comprises TGF-βs, bone morphogenetic proteins (BMPs), activins and related proteins. Signaling begins with the binding of a TGF beta superfamily ligand to a TGF beta type II receptor. The type II receptor is a serine/threonine receptor kinase, which catalyzes the phosphorylation of the Type I receptor. The type I receptor then phosphorylates receptor-regulated SMADs (R-SMADs) which can now bind the coSMAD (e.g. SMAD4). R-SMAD/coSMAD complexes accumulate in the nucleus where they act as transcription factors and participate in the regulation of target gene expression. Deregulation of TGF-β signaling contributes to developmental defects and human diseases, including cancers, some bone diseases, chronic kidney disease, etc.

MCE designs a unique collection of 223 TGF-beta/Smad signaling pathway compounds. TGF-beta/Smad Compound Library acts as a useful tool for TGF-beta/Smad-related drug screening and disease research.