SWI/SNF Family of Chromatin-Remodelling Complexes

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

GPCRs are a large family of cell surface receptors that respond to a variety of external signals. Binding of a signaling molecule to a GPCR results in G protein activation, which in turn triggers the production of any number of second messengers. GPCRs play an important role in the human body, and increased understanding of these receptors has greatly affected modern medicine. In fact, researchers estimate that between one-third to one-half of all approved drugs act by binding to GPCRs. GPCRs are a large group of drug targets in drug discovery.

MCE provides a unique collection of 2,832 small molecules targeting GPCRs that can be used in the screening for various GPCRs-related research and drug development projects.

The cytoskeleton is responsible for contraction, cell motility, movement of organelles and vesicles through the cytoplasm, cytokinesis, intracellular signal transduction, and many other functions that are essential for cellular homeostasis and survival. It accomplishes these tasks through three basic structures: F-actin, microtubules, and intermediate filaments (IFs). The cytoskeleton is a dynamic structure where the three major filaments and tubules are under the influence of proteins that regulate their length, state of polymerization, and level of cross-linking. Since cytoskeleton is involved in virtually all cellular processes, cytoskeletal protein aberrations are the underlying reason for many pathological phenotypes, including several cardiovascular disease syndromes, neurodegeneration, cancer, liver cirrhosis, pulmonary fibrosis, and blistering skin diseases.

MCE designs a unique collection of 1,543 cytoskeleton-related compounds mainly focusing on the key targets in the cytoskeleton signal pathway and can be used in the research of cytoskeleton signal pathway and related diseases.

Targeted Protein Degradation (TPD) is a novel and promising approach to drug development. It shows great potential for targeting proteins traditionally considered "undruggable" due to the lack of enzymatic function and absence of binding sites by tagging them for degradation or recruiting natural degradation mechanisms.

Molecular glues are a type of small-molecule degraders that primarily induce novel interactions between E3 ubiquitin ligases and target proteins, forming ternary complexes that lead to protein ubiquitination and subsequent proteasomal degradation. Compared with PROTACs, molecular glues generally have lower molecular weights, higher cell permeability, and better drug-like properties. Additionally, the design of molecular glues is relatively simple, without the requirements for complex linkers and ligand optimization. As a result, molecular glues have gradually emerged as a promising therapeutic approach for various diseases.

Multiple types of molecular glues have been reported previously. Analysis of co-crystal complex structures reveals that CRBN-, VHL-, and DCAF-related molecular glues are more versatile. Therefore, MCE researchers select active molecules related to these targets as probes for artificial intelligence (AI) screening.Subsequently, molecular docking technology was used to verify whether the screened molecules retained the key pharmacophore features. Ultimately, we obtained 1200 molecular glue analogs, and these compounds serve as powerful tools for the research of molecular glues.

Pulmonary fibrosis (PF), also known as diffuse interstitial pulmonary fibrosis, is a very common end-stage manifestation of several diseases, including idiopathic pulmonary fibrosis (IPF), pulmonary hypertension, and scleroderma, characterised by excessive matrix deposition and destruction of the lung architecture, finally leading to respiratory insufficiency. PF has become a global disease with significantly increased incidence rate, and the most common form of pulmonary fibrosis is idiopathic pulmonary fibrosis (IPF).

Lung fibrosis is a complex disease, a multitude of signal factors and signaling pathways is disrupted in this complex disease, such as TGF-β, Wnt, VEGF and PI3K–Akt. MCE offers a unique collection of 2,004 compounds with identified and potential anti-pulmonary fibrosis activity. MCE Anti-Pulmonary Fibrosis Compound Library is a useful tool for anti-pulmonary fibrosis drugs screening and other related research.

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

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 142 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.

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

MCE designs a unique collection of 2,671 apoptosis-related compounds mainly focusing on the key targets in the apoptosis signaling pathway and can be used in the research of apoptosis signal pathway and related diseases.

Stem cells, which are found in all multi-cellular organisms, can divide and differentiate into diverse special cell types and can self-renew to produce more stem cells. To be useful in therapy, stem cells must be converted into desired cell types as necessary which is called induced differentiation or directed differentiation. Understanding and using signaling pathways for differentiation is an important method in successful regenerative medicine. Small molecules or growth factors induce the conversion of stem cells into appropriate progenitor cells, which will later give rise to the desired cell type. There is a variety of signal molecules and molecular families that may affect the establishment of germ layers in vivo, such as fibroblast growth factors (FGFs); the wnt family or superfamily of transforming growth factors β (TGFβ) and bone morphogenetic proteins (BMP). Unfortunately, for now, a high cost of recombinant factors is likely to limit their use on a larger scale in medicine. The more promising technique focuses on the use of small molecules. These small molecules can be used for either activating or deactivating specific signaling pathways. They enhance reprogramming efficiency by creating cells that are compatible with the desired type of tissue. It is a cheaper and non-immunogenic method.

MCE Differentiation Inducing Compound Library contains a unique collection of 1,746 compounds that act on signaling pathways for differentiation. These compounds are potential stimulators for induced differentiation. This library is a useful tool for researching directed differentiation and regenerative medicine.

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 1,654 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 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 3,261 bioactive compounds targeting protein kinases, which is an important tool for the development of drug targeting protein kinases.

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 5,179 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

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 2,191 compounds that can be used for stem cell regulatory and signaling pathway research.

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 923 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.

5-HT receptors, also called Serotonin receptors, are a group of G protein-coupled receptors (GPCRs) and ligand-gated ion channels (LGICs) found in the central and peripheral nervous systems. These receptors are now classified into seven families, 5-HT1–7, comprising a total of 14 structurally and pharmacologically distinct mammalian 5-HT receptor subtypes. The 5-HT receptors influence various biological and neurological processes such as aggression, anxiety, appetite, cognition, learning, memory, mood, nausea, sleep, andthermoregulation. The serotonin receptors are the target of a variety of pharmaceutical drugs, including many antidepressants, antipsychotics, anorectics, antiemetics, gastroprokinetic agents, antimigraine agents, hallucinogens, and entactogens.

MCE 5-HT Receptor Compound Library consists of 340 5-HT receptor inhibitors and activators, which can be used for neuropsychiatric disorders drugs discovery.

Orthopoxvirus is a genus of viruses in the family Poxviridae and subfamily Chordopoxvirinae. The orthopoxvirus genus consists of 12 viruses including variola virus, vaccinia virus (VV), cowpox viruses (CV), monkeypox virus, and camelpox virus. Smallpox has been eradicated worldwide in 1980, but some other orthopoxvirus, such as monkeypox virus, are still threats to human health.

There are not many drugs available for orthopoxvirus treatment. The only product currently available for treatment of complications of Orthopoxvirus infection is vaccinia immunoglobulin (VIG). In 2021, brincidofovir was approved by FDA for the treatment of smallpox and tecovirimat was approved by EMA for the treatment of monkeypox in 2022. A few active compounds including interferon and interferon inducers, and a variety of nucleosides or nucleotides have been reported to have activity against orthopoxvirus.

MCE carefully prepared a unique collection of 36 compounds reported with the anti- orthopoxvirus activity which can be used for drug screening and other research about orthopoxvirus.

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 1,258 compounds that act as a useful tool for PTKs-related drug screening and disease research.

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 553 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).

Cell proliferation, the increase in cell numbers resulting from cell division, is a complex and tightly regulated process. Cell proliferation is regulated by coordinated entry into the cell cycle, and changes in proliferation are closely linked to disease development. Evolutionary dynamics links tumor growth and progression with cell proliferation, cell death, and mutation rates. In addition, cell proliferation is central to degenerative diseases, the development of which is often accompanied by accelerated multiplication of cancer cells. Therefore, assays of cell proliferation levels are frequently used for laboratory research purposes and increasingly for clinical assessment of tumor aggressiveness and potentially to guide care. It has been shown that multiple key targets are collectively involved in regulating the process of cell proliferation, such as CDK, E2F, pRB, β-Catenin, and others.

MCE collects 2,448 compounds that target and regulate key targets of cell proliferation, which can be used in studies of cell proliferation mechanisms and drug discovery.

Targeted protein degradation(TPD) is a novel and promising approach to new drug discovery and development. It shows great potential for treating diseases with “undruggable” pathogenic protein targets and for overcoming drug resistance. Molecular glues and PROTACs are both targeted protein degraders that have attracted the most attention.

Molecular glues are small molecular degraders that mainly induce novel interaction between an E3 ligase and a target protein to form a ternary complex, leading to protein ubiquitination and subsequent proteasome degradation. Compared with PROTACs, molecular glues generally possess more favorable drug-like properties, such as lower MW, higher cell permeability, and better oral absorption. Molecular glues are emerging as a promising new therapeutic strategy.

MCE supplies a unique collection of 55 molecular glues which target various proteins. MCE Molecular Glue Compound Library is a useful tool to conduct scientific research and disease mechanism study.

The occurrence of diseases is often associated with multiple targets and pathways, and the factors of disease formation are complex and diverse, so the development of more powerful drugs is needed. According to statistics, 21% of the FDA-approved drugs in 2015-2017 were multi-target compounds. Multi-target compounds refer to a drug targeting multiple disease-related targets or multiple subtypes of a target. Multi-target compounds can be applied to drug screening or targeted ligand design. Because the targets of such compounds are diverse and clear, they have the characteristics of saving time and drug cost during the mechanism research of new drug research and development. In addition, due to the diversity of drug targets, multiple strategies can be applied to pharmacological studies.

MCE supplies a unique collection of 4,883 multi-target compounds that targets two or more different targets or different subtypes of the same target. MCE Multi-Target Compound Library can be used for target protein ligand screening or drug development.

Inflammasomes are classic pattern recognition receptors for natural immune responses. Inflammasomes are polymeric protein complexes that regulate inflammatory responses and pyrolytic cell death, thereby exerting the host's defense against microorganisms. Inflammasomes sensors are associated with adapter proteins, activating inflammatory caspase-1, releasing inflammatory cytokines and inducing cell death, endowing the host with defense against pathogens. NLRP1, NLRP3, NLRC4, AIM2, and pyrin are considered typical inflammasomes because they convert cysteine asparaginase-1 into catalytically active capsaicin-1. In addition to infectious diseases, the importance of inflammasomes is also related to various clinical diseases, such as autoimmune diseases, neurodegeneration and metabolic disorders, and the development of cancer. Therefore, it is necessary to strictly regulate the activation and function of inflammasomes to avoid accidental host tissue damage while inducing pathogens to kill the inflammatory response.

MCE designs a unique collection of 92 inflammasomes related compounds. It is a good tool to be used for research on Inflammation, cancer and other diseases.

Miao medicine is an important part of Chinese medicine, which carries the profound cultural heritage and rich life wisdom of the Hmongb people. Miao people live in a concentrated community in the mountainous area of the southwest border of China, which has a unique natural environment. Complex and diverse geology, lush natural vegetation, rich animal and plant species, a large number of mineral resources which provide a wide range of species sources for miao ethnicity medicine. On the other hand, due to the characteristics of the living environment of the Hmongb people, Miao medicine has demonstrated its unique therapeutic effect in the treatment of some endemic diseases, infectious diseases, insect, snake and beast bites, rheumatism and other diseases. With the development of modern science and technology, the research and application of seedling medicine are also deepening. Through the systematic study of the chemical composition and pharmacological action of the seedling medicine, it can provide a new idea and method for modern medicine.

MCE included 1,656 natural products from traditional miao ethnicity medicine, including animal, plant and mineral sources.

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

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

MCE carefully prepared a unique collection of 65 ligands for E3 ligase, which have been reported to be used in PROTAC design. MCE E3 ligase ligand library is a useful tool for PROTAC development.

Tuberculosis (TB), usually caused by bacteria (Mycobacterium tuberculosis), is an infectious disease that mainly affects the lungs. According to the statistics of the World Health Organization (WHO), 10 million people suffer from tuberculosis every year, and 1.5 million people die of tuberculosis every year, which makes tuberculosis the number one killer of infectious diseases.

Tuberculosis can be cured through the standard 6-month course of treatment of four kinds of antibiotics. Common drugs include rifampicin and isoniazid. In some cases, TB bacteria do not respond to standard drugs, that is, patients with drug-resistant tuberculosis. The treatment of drug-resistant tuberculosis takes longer and is more complex. In the face of the resurgence of tuberculosis in the world and the rapid emergence of multi drug resistant tuberculosis, it is very important to develop new anti-tuberculosis drugs or new clinical treatment schemes for existing anti mycobacterium drugs.

MCE supplies a unique collection of 116 compounds with clear anti-tuberculosis activity. MCE Anti-tuberculosis Compound Library is a useful tool for anti-tuberculosis related research and anti-tuberculosis drug development

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 5,358 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.

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 294 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.

Hepatitis C virus (HCV) is a hepatotropic enveloped positive- strand RNA virus (family Flaviviridae) that infects the parenchymal cells of the liver. HCV infection is a significant public health burden. Globally, an estimated 71 million people have chronic hepatitis C virus infection. A significant number of those who are chronically infected will develop cirrhosis or liver cancer. To date, there is no vaccine against HCV, and combination pegylated alpha interferon (pIFN-) and ribavirin, the main standard-of-care treatment for HCV, is effective in only a subset of patients and is associated with a wide spectrum of toxic side effects and complications. More recently, new therapeutic approaches that target essential components of the HCV life cycle have been developed, including direct-acting antiviral (DAA) that specifically block a viral enzyme or functional protein and host-targeted agents (HTA) that block interactions between host proteins and viral components that are essential to the viral life cycle. However, the genetic diversity of HCV viruses and the stage of liver disease (i.e., cirrhosis) are revealing themselves as obstacles for effective, pan-genotypic treatments. There still exists a need for the discovery and development of new HCV inhibitors. In particular, since the future of HCV therapy will likely consist of a cocktail approach using multiple inhibitors that target different steps of infection, new antivirals targeting all steps of the viral infection cycle.

MCE offers a unique collection of 334 compounds with identified and potential anti-HCV activity. MCE Anti- Hepatitis C Virus Compound Library is a useful tool for discovery new anti-HCV drugs and other anti-infection research.