NIMA (never in mitosis gene a)-related Expressed Kinases

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 3,157 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.

The most prominent mechanism of action of kinase inhibitors is their competition with ATP by binding to the hinge region of the kinase protein. Once the kinase is blocked by an inhibitor, it loses the ability to transfer phosphate groups from ATP to other molecules, resulting in the loss of kinase activity.

The hinge-binding region of kinase inhibitors mimics the interaction pattern between the ATP nucleobase and the kinase. MCE extracted thousands of kinase inhibitors from the ChEMBL database and isolated their molecular fragments. In certain cases, the amino and amide groups on the molecular fragments are crucial for binding in the hinge region. Therefore, we enhanced the diversity of the collected results by adding these two groups to unoccupied positions on the ring system. Subsequently, the fragments were assessed for their hinge region binding ability via docking at distinct kinases, we also applied pharmacophore constraints to ensure interactions with key amino acids in the kinase hinge region, ultimately obtaining kinase-related molecular fragments.

MCE provides over 10,000 kinase fragment molecules that meet the above requirements and are available off the shelf, serving as an effective tool for screening and developing drugs targeting kinases.

Protein Kinases (PTKs) are a class of phosphotransferases that phosphorylate proteins. Protein kinases participate in many signal transduction pathways including those involved with growth, differentiation, and cell division. Protein kinase not only plays an important role in the process of cell activation, but also its abnormal expression is closely related to the pathogenesis of many diseases. So far, the protein kinase family has become one of the most important drug targets. The most common drug targets include ALK, B-Raf, BCR-Abl, EGFR, and VEGFR.

MCE designs a unique collection of 3,351 bioactive compounds targeting protein kinases, which is an important tool for the development of drug targeting protein kinases.

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 1,544 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.

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 1,280 compounds that act as a useful tool for PTKs-related drug screening and disease 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 2,560 cell cycle/DNA damage-related compounds which can be used in the research of the same.

According to reports, most known kinase inhibitors exert their effects through competitive binding in highly conserved ATP pockets. Although genetic techniques such as RNA interference can inactivate specific genes, most kinases are multi domain proteins, each of which has an independent function. Highly selective inhibitors have higher efficiency than non-selective inhibitors, and the selectivity to the target is at least 100 times higher. Therefore, ensuring the validation of targets with the most selective inhibitors is crucial for a more thorough understanding of the pharmacology of the kinase field. The Highly Selective Inhibitors Library contains 5,270 compounds, covering multiple targets and subtypes, such as GPCR protein family, Ion channel, multiple kinases, etc. The Highly Selective Inhibitors Library is an effective tool for screening different phenotypes

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 705 MAPK signaling pathway inhibitors that act as a useful tool for MAPK-related drug screening and disease research.

Glucose homeostasis is tightly regulated to meet the energy requirements of the vital organs and maintain an individual’s health. Glucose metabolism includes glycolysis, tricarboxylic acid cycle, pentose phosphate pathway, oxidative phosphorylation and other metabolic pathways. Glucose is the major carbon source that provides the main energy for life. Glucose metabolism dysregulation is also implicated in many diseases such as diabetes, heart disease, neurodegenerative diseases and even cancer.

MCE offers a unique collection of 1,220 compounds related to glucose metabolism, which target glucose metabolism related targets, such as GLUT, Hexokinase, Pyruvate Kinase, IDH, etc. MCE glucose metabolism library is a powerful tool for studying glucose metabolism and drug discovery of diseases related to glucose metabolism.

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 9,162 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.

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 888 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.

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 2,300 compounds that can be used for stem cell regulatory and signaling pathway research.

MCE Targeted Diversity Library contains 2,299 compounds, covering more than 1000 targets and isoforms, such as GPCRs, Ion channel, variety of kinases, etc. 1-3 compounds with high potency and selectivity were carefully selected for each target and isoform. The bioactivity information of each compound has been clearly reported in the literatures. This library is a concise collection of small molecule compounds with comprehensive target coverage, which can be used for phenotypic screening at low cost.

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 942 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.

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 2,412 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.

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 2,239 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.

Agonistic drugs activate or stimulate their receptors, triggering responses that increase or decrease cell activity. The highly selective activators can act on specific biological or molecular targets, while non-selective activators may interfere with multiple targets or targets simultaneously. The highly selective activators reduce the likelihood of these non-specific effects by targeting specific targets, making research more precise and reliable. The Highly Selective Activators Library contains 1,691 compounds, covering multiple targets and subtypes, such as GPCR protein family, Ion channel, multiple kinases, etc. The Highly Selective Activators Library is an effective tool for screening different phenotypes.

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 148 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.

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 307 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.

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 738 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.

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 632 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.

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 3,269 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.

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 525 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 Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is central to signaling by cytokine receptors, a superfamily of more than 30 transmembrane proteins that recognize specific cytokines, and is critical in blood formation and immune response. Canonical JAK/STAT signaling begins with the association of cytokines and their corresponding transmembrane receptors. Activated JAKs then phosphorylate latent STAT monomers, leading to dimerization, nuclear translocation, and DNA binding. In mammals, there are four JAKs (JAK1, JAK2, JAK3, TYK2) and seven STATs (STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, STAT6). Since the JAK/STAT pathway plays a major role in many fundamental processes, such as apoptosis and inflammation, dysfunctional proteins in the pathway may lead to a number of diseases. For example, alterations in JAK/STAT signalling can result in cancer and diseases affecting the immune system, such as severe combined immunodeficiency disorder (SCID).

MCE provides 536 compounds that can be used in the study of the JAK/STAT signaling pathway and related diseases.

Ion channel is a membrane-binding enzyme whose catalytic site is an ion conduction pore, which is opened and closed in response to specific environmental stimuli (voltage, ligand concentration, membrane tension, temperature, etc.). Ion channel provide pores for the passive diffusion of ions on the biofilm. Due to their high selectivity for ion, ion channel are generally classified as sodium (Na⁺ ), potassium (K⁺ ), calcium (Ca²⁺ ), chloride (Cl^- ), and non-specific cation channel. Ion channel is an important contributor to cell signal transduction and homeostasis. In addition to electrical signal transduction, ion channel also have many functions: regulating vascular smooth muscle contraction, maintaining normal cell volume, regulating glandular secretion, protein kinase activation, etc. Therefore, dysfunction of ion channel can lead to many diseases, and its mechanism research is particularly important.

MCE designs a unique collection of 1,371 small molecules related to ion channel, mainly targeting Na⁺ channel, K⁺ channel, Ca²⁺ channel, GABA receptor, iGluR, etc. It is an essential tool for research of cardiovascular diseases, Nervous system diseases and other diseases.

Epigenetics refers to changes in phenotype that are not rooted in DNA sequence. Many types of epigenetic processes have been identified, including DNA methylation, alteration in the structure of histone proteins and gene regulation by small noncoding microRNAs. Modification of DNA, protein, or RNA, resulting in changes to the function and/or regulation of these molecules, without altering their primary sequences, reveals the complexities of cellular differentiation, embryology, the regulation of gene expression, aging, cancer, and other diseases.

MCE provide a unique collection of 1,546 epigenetics-related compounds that can be used in the research of the related diseases.

Dopamine receptor (DAR), widely distributed in the brain, plays a key role in regulating motor function, motivation, driving force and cognition. The role of DA is mediated by D1-type (D1, D5) and D2-type receptors (D2S, D2L, D3, D4), which are distributed in presynaptic, postsynaptic and extrasynaptic, projection neurons and interneurons. Each receptor has a different function. D1 and D5 receptors couple with G stimulation sites and activate Adenylyl cyclase. The activation of Adenylyl cyclase leads to the production of the second messenger cAMP, which leads to the production of protein kinase A (PKA), which leads to further transcription in the nucleus. D2 to D4 receptors are coupled to G inhibitory sites to inhibit adenylyl cyclase and activate potassium Ion channel. These receptors utilize phosphorylation cascades or direct membrane interactions to affect the functions of voltage-gated and neurotransmitter-gated channels, cytoplasmic enzymes, and transcription factors. Dopamine receptor plays an important role in daily life.

MCE designs a unique collection of 228 small molecules related to dopamine receptor. It is a good tool for screening drugs from nervous system disease.

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 1,715 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.

Pancreatic cancer is a devastating disease with a low overall survival rate. Chemotherapy is the most common treatment for patients presenting with advanced pancreatic cancer. More recently, the era of targeted therapies has generated a lot of interest in discovering better approaches for patients with pancreatic cancer. Commonly mutated genes in pancreatic cancer include K-ras (in 74-100% of cases), p16INK4a (up to 98%), p53 (43 to 76%), DPC4 (about 50%), HER-2/neu (in about 65%) and FHIT (found in 70% of cases). Other genes involved are notch1, Akt-2, BRCA2 and COX-2. These proteins are important targets of target therapies for pancreatic cancer.

MCE offers a unique collection of 3,250 compounds with identified and potential anti- pancreatic cancer activity. These compounds target K-Ras, p53, HER2, Notch, AKT, etc. MCE anti-pancreatic cancer compound library is a useful tool for anti-pancreatic cancer drugs screening and other related research.

Methylation is an epigenetic modification mechanism that involves adding methyl groups to molecules such as DNA and histones, which can alter gene expression without changing the DNA sequence. This process is catalyzed by enzymes such as DNA methyltransferases (DNMTs) and histone methyltransferases (HMTs), and can be reversed by demethylases. The balance of methylation and demethylation is crucial for maintaining cellular function and genomic stability. Abnormal regulation of methylation may lead to a variety of diseases, including cancer, neurological disorders, and developmental abnormalities. A deep understanding of the molecular mechanisms of methylation metabolism is essential for developing therapeutic strategies for diseases associated with methylation dysregulation.

MCE contains 287 compounds targeting methylation/demethylation enzymes, which is of significant value for studying the pathways of methylation metabolism and exploring their mechanisms of action in diseases.

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 828 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.

Hematopathy, also known as hematopoietic system diseases, are a class of diseases that hematopoietic system has abnormal changes. Common hematopathy include: aplastic anemia, myeloproliferative diseases, thalassemia, leukemia, lymphoma, myeloma and hemophilia, etc. In recent years, treatments for hematopathy have been developed. In particular, the treatment of malignant hematopathy developed from chemotherapy, radiotherapy, bone marrow development to immunotherapy, induced differentiation therapy, cell therapy, gene therapy and hematopoietic stem cell transplantation. Although these therapies have greatly improved the survival rate of patients, there are still problems such as low cure rate and easy recurrence in the treatment of hematopathy. Therefore, it is of great significance to actively search for new hematopathy therapeutic drugs.

MCE designs a unique collection of 3,290 anti-hematopathy small molecules, which is an effective tool for development and research of anti-hematopathy compounds.

Metabolomics is the large-scale study of cellular metabolic complement, with proven utility in both basic and applied studies of plants, microorganisms, and mammals. As an important tool for the study of complex biological systems, metabolomics monitors the complex molecular networks that exist in the natural flow of information from genes to mRNA and proteins to organisms. The metabolome is composed of biomolecules that most closely resemble the phenotype of an organism, and changes in its composition can easily lead to the production of diseases. Therefore, metabolomics has received much attention in drug target discovery, drug response and translational research of disease mechanisms. Mass spectrometry-based metabolomics methods can simultaneously detect and quantify thousands of metabolite signatures, thereby characterizing the pathophysiological mechanisms of various biomedical symptoms.

MCE can provide 673 mass spectrometry human endogenous metabolites that can be used for metabolite identification and quantification, functional cell detection and phenotypic screening of mass spectrometry.

A histone modification, a covalent post-translational modification (PTM) to histone proteins, includes methylation, phosphorylation, acetylation, ubiquitylation, and sumoylation, etc. In general, histone modifications are catalyzed by specific enzymes that act predominantly at the histone N-terminal tails involving amino acids such as lysine or arginine, as well as serine, threonine, tyrosine, etc. The PTMs made to histones can impact gene expression by altering chromatin structure or recruiting histone modifiers. Histone modifications act in diverse biological processes such as transcriptional activation/inactivation, chromosome packaging, and DNA damage/repair. Deregulation of histone modification contributes to many diseases, including cancer and autoimmune diseases.

MCE owns a unique collection of 748 bioactive compounds targeting Epigenetic Reader Domain, HDAC, Histone Acetyltransferase, Histone Demethylase, Histone Methyltransferase, Sirtuin, etc. Histone Modification Research Compound Library is a useful tool for histone modification research and drug screening.

Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, arises as adenocarcinoma from glandular epithelial cells of the large intestine comprised of the colon and rectum. The majority of cases of CRC are sporadic and result from risk factors, such as a sedentary lifestyle, obesity, processed diets, alcohol consumption and smoking. CRC is also a common preventable cancer.

Studies showed several cellular signaling pathways dysregulated in CRC, leading to the onset of malignant phenotypes. Therefore, it is necessary to analyze the signaling pathways involved in the occurrence and development of colorectal cancer to study the progression and drug treatment of colorectal cancer. Among them, Wnt/β-catenin, p53, TGF-β/SMAD, NF-κB, Notch, VEGF and other target genes and signaling pathways are the focus of research. MCE offers a unique collection of 1,932 compounds with identified and potential anti-colorectal cancer activity. MCE anti-colorectal cancer compound library is a useful tool for anti-colorectal cancer drugs screening and other related research.

Most of molecules enter or leave cells mainly via membrane transport proteins, which play important roles in several cellular functions, including cell metabolism, ion homeostasis, signal transduction, the recognition process in the immune system, energy transduction, etc. There are three major types of transport proteins, ATP-powered pumps, channel proteins and transporters. Transport proteins such as channels and transporters play important roles in the maintenance of intracellular homeostasis, and mutations in these transport protein genes have been identified in the pathogenesis of a number of hereditary diseases. In the central nervous system, ion channels have been linked to, but not limited to, many diseases such asataxias, paralyses, epilepsies, and deafness. This indicates the roles of ion channels in the initiation and coordination of movement, sensory perception, and encoding and processing of information. Ion channels are a major class of drug targets in drug development.

MCE designs a unique collection of 1,739 smal-molecule modulators that can be used for the research of Ion Channel and Membrane Transporter or high throughput screening (HTS) related drug discovery.

Nuclear factor-κB (NF-κB)/Rel proteins include NF-κB2 p52/p100, NF-κB1 p50/p105, c-Rel, RelA/p65, and RelB. These proteins function as dimeric transcription factors that regulate the expression of genes and influence a broad range of biological processes including innate and adaptive immunity, inflammation, stress responses, B-cell development, and lymphoid organogenesis. NF-κB plays a key role in regulating the immune response to infection. In addition, activation of the NF-κB pathway is involved in the pathogenesis of chronic inflammatory diseases, such as asthma, rheumatoid arthritis, and inflammatory bowel disease. Incorrect regulation of NF-κB has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development.

MCE owns a unique collection of 1,105 small molecule compounds that can be used in the research of NF-κB signaling pathway or high throughput screening (HTS) related drug discovery.

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 2,228 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.

Aging is a complex biological process characterized by functional decline of tissues and organs, structural degeneration, and reduced adaptability and resistance, all of which contribute to an increase in morbidity and mortality caused by multiple chronic diseases, such as Alzheimer's disease, cancer, and diabetes. Many theories, which fall into two main categories: programmed and error theories, have been proposed to explain the process of aging, but neither of them appears to be fully satisfactory. The programmed theories imply that aging relies on specific gene regulation, and the error theories emphasize the internal and environmental damages accumulated to living organisms. The damage theories proposed the nine hallmarks that were generally considered to contribute to the aging process: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient-sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication.

MCE Anti-Aging Compound Library contains 5,592 compounds, mainly targeting Sirtuin, mTOR, IGF-1R, AMPK, p53, Telomerase, Mitophagy, Mitochondrial Metabolism, COX, Cytochrome P450, Oxidase, etc. This library is a useful tool for anti-aging research.

Liposomes are spherical or multilayered spherical vesicles formed by the self-assembly of diacyl chain phospholipids (lipid bilayers) in aqueous solutions, which can be made from natural or synthetic phospholipids and exhibit good biocompatibility and low toxicity. They can serve as delivery carriers for various bioactive substances (such as drugs, proteins, nucleic acids, etc.) and are widely used in biomedical and chemical research. The main advantages of liposomes include 1) Protective effect: Their bilayer structure can protect encapsulated molecules from enzymatic degradation, oxidation, and other influences, extending stability and activity; 2) Active targeting: Surface modifications enable active targeting, enhancing the concentration of drugs or molecules in specific tissues or cells; 3) Customizability: The composition and structure of liposomes can be adjusted according to needs, such as altering phospholipid types or adding targeting ligands. These properties make liposomes highly valuable in developing novel drug delivery systems, serving as nucleic acid carriers for gene transfection, studying cellular uptake mechanisms and drug release kinetics, as well as developing functional food additives to improve the bioavailability of nutritional components.

MCE contains 137 liposome compounds, which is a good tool for lipidomic-related studies.

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 2,620 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.

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 2,566 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.