cell permeability

Normal mitochondrial function is critical for maintaining cellular homeostasis because mitochondria produce ATP and are the major intracellular source of free radicals. Cellular dysfunctions induced by intracellular or extracellular insults converge on mitochondria and induce a sudden increase in permeability on the inner mitochondrial membrane, the so-called mitochondrial membrane permeability transition (MMPT). MMPT is caused by the opening of pores in the inner mitochondrial membrane, matrix swelling, and outer membrane rupture. The MMPT is an endpoint to initiate cell death because the pore opening together with the release of mitochondrial cytochrome c activates the apoptotic pathway of caspases.

The normal operation of mitochondrial function is important for maintaining normal cell death and treatment of mitochondrial diseases. MCE offers a unique collection of 771 compounds with identified and potential mitochondrial protective activity. MCE Mitochondrial Protection Compound Library is critical for drug discovery and development.

Chemical probes are simply reagents with high potency, selectivity and cell-permeability which play important roles in both fundamental and applied biological research. In their most common application, chemical probes can establish the tractability of a specific target. They are used to interrogate the relationship between a target and its phenotype (biological tractability) as well as an ability to modulate that phenotype using a small molecule. Otherwise, chemical probes also have had a major impact in enabling and accelerating discoveries along the path to pioneer medicines. They have helped to improve the understanding of targets and pathways and have created opportunities for proprietary drug discovery efforts to an extent that would not have been possible otherwise.

MCE provides a unique collection of 279 chemical probes with high potency (at least 100 nM potency), selectivity (at least 10-fold selectivity against any other target) and cell-permeability (at least 10 μM potency). MCE Chemical probe library is a useful tool for target identification and mechanism research.

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 2,505 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.

Mitochondria plays an important role in many vital processes in cells, including energy production, fatty-acid oxidation and the Tricarboxylic Acid (TCA) cycle, calcium signaling, permeability transition, apoptosis and heat production. At present, it is recognized that many diseases are associated with impaired mitochondrial function, such as increased accumulation of ROS and decreased OXPHOS and ATP production. Mitochondria are recognized as one of the most important targets for new drug design in cancer, cardiovascular, and neurological diseases, etc. Some small molecule drugs or biologics can act on mitochondria through various pathways, including ETC inhibition, OXPHOS uncoupling, mitochondrial Ca²⁺ modulation, and control of oxidative stress via decrease or increase of mitochondrial ROS accumulation.

MCE supplies a unique collection of 1,124 mitochondria-targeted compound that mainly targeting Mitochondrial Metabolism, ATP Synthase, Mitophagy, Reactive Oxygen Species, etc. MCE Mitochondria-Targeted Compound Library is a useful tool for mitochondria-targeted drug discovery and related research.

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.

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.

With the progress of modern cancer therapy, the life of cancer patients has been extended. However, after initial treatment and recovery, the development of secondary tumors often leads to cancer recurrence. Cancer stem cells are a small number of cells that tumor growth and reproduction depend on.

Cancer stem cells have strong self-renewal ability, which is the direct cause of tumor occurrence. In addition, cancer stem cells also have the ability to differentiate into different cell types, playing a crucial role in tumor metastasis and development. Chemotherapy and radiotherapy induced DNA damage and apoptosis are common cancer treatments. However, cancer stem cells can effectively protect cancer cells from apoptosis by activating DNA repair ability. Cancer stem cells are regarded as the key "seed" of tumor occurrence, development, metastasis and recurrence. Since its first discovery in leukemia in 1994, cancer stem cells have been considered a promising therapeutic target for cancer treatment.

MCE supplies a unique collection of 2,539 compounds targeting key proteins in cancer stem cells. MCE Cancer Stem Cells Compound Library is a useful tool for cancer stem cells related research and anti-cancer drug development.

Antibody inhibitors are compounds with the same activity as the original therapeutic antibodies, which can be used as positive controls for drug efficacy evaluation and other studies. Antibody inhibitors can also assist in verifying the functional activity of the target protein. These antibody inhibitors are active in vivo and can achieve certain physiological functions by blocking or neutralizing target proteins, such as CD20, HER2, EGFR, VEGFR, TNF-α, etc. In drug screening, antibody inhibitor-based screening can be carried out to identify active compounds targeting target proteins and target diseases.

MCE can provide 1,023 antibody inhibitors that can be used for drug development in cancer, immunity, infection and other hot research areas.

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 4,911 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.

PROTACs (Proteolysis-targeting chimeras) is a class of molecules that utilize ubiquitin-proteasome system (UPS) to ubiquitinate and degrade target proteins. The PROTACs molecule consists of two ligands joined by a linker. The one-to-one interaction between PROTACs and target proteins determines the high efficiency of PROTACs, making it a potential molecule for targeted protein degradation (TPD) therapy.

MCE supplies a unique collection of 340 PROTACs that effectively degrade target proteins with more powerful screening capability. MCE PROTAC Library is a useful tool for signal pathway research, protein degradation therapy research, drug discovery and drug repurposing, etc.

Bioactive compounds are a general term for a class of substances that can cause certain biological effects in the body, which are the main source of small molecule drugs. These compounds generally penetrate cell membranes, act on specific target proteins in cells, regulate intracellular signaling pathways, and cause some changes in cell phenotype.

MCE owns a unique collection of 26,001 compounds with confirmed biological activities and clear targets. These compounds include natural products, innovative compounds, approved compounds, and clinical compounds. This library is a useful tool for signal pathway research, drug discovery and drug repurposing, etc.

Bioactive Compound Library Plus, with more powerful screening capability, further complements Bioactive Compound Library (HY-L001) by adding some compounds with low solubility or solution stability (Part B) and some novel, rare or exclusive compounds (Part C) to this library. Overall, bioactive compound library plus (HY-L001P) includes tree parts: Part A, Part B and Part C. Compounds in Part A are equal to the products in HY-L001, which can be supplied in solution or solid form. Compounds in Part B and C are only supplied in solid form.

Cell death plays a crucial role in the development of the body and the maintenance of internal balance to prevent the development of diseases. According to the regulation of the involved processes, cell death can be defined as programmed and non-programmed death. Programmed cell death (PCD) can be divided into lytic cell death and nonlytic cell death, mainly including apoptosis, necrotic apoptosis and Pyroptosis. Non-Programmed cell death (Non-PCD) generally refers to necrosis. In stark contrast to Accidental Cell Death (ACD), Regulatory Cell Death (RCD) relies on specialized molecular mechanisms. Cell death includes internal apoptosis, external apoptosis, necrotic apoptosis, ferroptosis, pyroptosis, lysosome-dependent cell death, etc.

MCE designs a unique collection of 2,830 cell death compounds, covering multiple targets, such as Apoptosis, Ferroptosis, Pyroptosis, Necroptosis, etc. It is a useful tool for screening cell death drugs.

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 2,209 compounds that can be used for stem cell regulatory and signaling pathway research.

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 2,467 compounds that target and regulate key targets of cell proliferation, which can be used in studies of cell proliferation mechanisms and drug discovery.

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

MCE contains 495 mitochondrial toxic compounds, which can be used as tool compounds for drug development and disease mechanism 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 2,468 cell cycle/DNA damage-related compounds which can be used in the research of the same.

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

MCE offers a unique collection of 92 cyclic peptides, all of which have good bioactivities. MCE Cyclic Peptide Library is a powerful tool for drug discovery and PPI inhibitor screening.

Bioactive compounds are a general term for a class of substances that can cause certain biological effects in the body, which are the main source of small molecule drugs. These compounds generally penetrate cell membranes, act on specific target proteins in cells, regulate intracellular signaling pathways, and cause some changes in cell phenotype.

MCE owns a unique collection of 21,181 compounds with confirmed biological activities and clear targets. These compounds include natural products, innovative compounds, approved compounds, and clinical compounds. These can also be used for signal pathway research, drug discovery and drug repurposing, etc.

Cancer is the second leading cause of death globally and seriously threatens human health. A neoplasm and malignant tumor are other common names for cancer. Disruption of the normal regulation of cell-cycle progression and division lies at the heart of the events leading to cancer. Target therapy, which targets proteins that control how cancer cells grow, divide and spread, plays an important role in cancer treatment. Recent studies mainly focus on targeting the key proteins for cancer surviving, cancer stem cells, the tumor microenvironment, tumor immunology, etc.

MCE designs a unique collection of 8,927 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 2,350 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.

Antibody-Drug Conjugates (ADCs), a new class of treatment for cancer, are composed with a monoclonal antibody, a linker and a cytotoxic agent also referred to as a payload. To date, several ADCs have received market approval and more than 60 ADCs are currently in clinical trials. ADCs are one of the fastest growing classes of oncology drugs worldwide.

The payload or cytotoxic agent is the most important unit in the ADC. ADC has the capability to kill cancer cell depending on the potency of the payload. MCE provides 111 highly potent cytotoxins that contain auristatin derivatives, maytansinoids, calicheamicin, duocarmycin, pyrrolobenzodiazepines (PBDs), etc.

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

MCE offers a unique collection of 51 animal model inducers, involving inflammatory model, tumor model, nervous disease model, etc. MCE Animal Disease Model library is a powerful tool for the establishment of animal disease models.

Peptides are a group of biologically active substances that are involved in various cellular functions of organisms. Peptides are often used in functional analysis, vaccine research and especially in the field of drug research and development. At present, more than 80 peptide drugs have reached the market for a wide range of diseases, including diabetes, cancer, osteoporosis, multiple sclerosis, HIV infection and chronic pain.

MedChemExpress (MCE) offers a comprehensive collection of 1,783 peptides, including bioactive peptides, amino acid derivatives, and blocking peptides. MCE Peptide Library can be used for peptide library screening, peptide drug discovery, vaccine development, target verification, structural activity research, etc.

A drug metabolite is a byproduct of the body breaking down, or “metabolizing” a drug into a different substance. Most drugs undergo chemical alteration by various bodily systems as a way to create compounds that are more easily excreted from the body. Drugs can be metabolized by oxidation, reduction, hydrolysis, hydration, conjugation, condensation, or isomerization. Drug metabolism can produce metabolites with physicochemical and pharmacological properties that differ substantially from those of the parent drug, and consequently have important implications for both drug safety and efficacy.

MCE offers a unique collection of 270 drug metabolites which is a useful tool for drug safety and efficacy study and drug repurposing.

The lack of availability of appropriate medicines for children is an extensive and urgent problem. A variety of obstacles hinder children's drug development, including the limited commercial interest, lack of suitable infrastructure and competence for conducting paediatric clinical trials, difficulties in trial design, ethical worries and many others. Because of these factors, unlicensed and off-label prescribing is very common in children which may lead to safety concern.

MCE offers a unique collection of 682 Pediatric medicines, all of which have been approved or studied in clinical trials for children diseases. MCE children’s drug library is a useful tool for drug repurposing to discover new children’s indications.

The anti-cancer drug library meticulously collects all drugs approved by FDA and other major national drug regulatory authorities for cancer treatment. These drugs cover a variety of cancer types, including but not limited to lung cancer, breast cancer, colorectal cancer, leukemia, and other common cancers. The library includes a wide range of drugs, from classic chemotherapeutic agents to cutting-edge targeted therapies and immunotherapies. It contains various types of drug compounds with different mechanisms of action. There are cytotoxic drugs that directly kill cancer cells, as well as drugs that work by modulating the tumor microenvironment, inhibiting tumor angiogenesis, and activating the immune system. This diversity provides researchers with a broad range of perspectives and options for intervention strategies.

This library can be used for basic research on cancer treatment, exploring new targets and new mechanisms of drug action; Conducting drug reuse research to look for potential therapeutic effects of existing drugs on other cancer types or diseases; Or conducting research into combination drugs to optimize cancer treatment.

MCE has collected 283 small-molecule compounds with cancer indications, which are good tools for drug repurposing.

Food additives are substances added to food to maintain or improve its safety, freshness, taste, texture, or appearance. All food additives used in food undergo a safety assessment, which includes rigorous testing, before they are approved, so all food additives are generally recognized as safe substances.

MCE supplies 435 approved food additives which are safe substances and can be used for drug discovery and other research.

Flavor is an expression of smell and taste that is achieved through a variety of chemical processes triggered by molecules. Food flavor is an important attribute of food quality and in some cases determines consumers' food preferences. In addition to playing a key role in taste and smell, flavor molecules can also be involved in regulating metabolism and have an impact on health. In daily life, flavor molecules have absolute application value in food and spices. In scientific research, the study of flavor molecules is helpful to reveal the relationship between food intake and taste perception. Research on the combination behavior of flavor and food components can explore the retention, release and perception of flavor molecules. Most importantly, while exploring multi-sensory flavor perception, the food industry can fully mobilize the enthusiasm of researching new strategies for delicious and healthy food design.

Based on the FlavorDB database, collects and organizes 410 flavor molecules, which can be used in taste perception and other related studies.

Withdrawal or delisting drugs refer to drugs that are recalled or discontinued from the market due to low efficiency, serious side effects, financial and regulatory problems and other reasons. Once the drug is withdrawn from the market, it will cause heavy losses to the original research company that invested a lot of time, finance and other costs to develop the drug.

Adverse drug reaction (ADR) is the main reason for drug withdrawal from the market. ADR refers to the unexpected effects caused by the reasons such as the target-directed interaction during the treatment. However, studying the mechanism of these ADRs may just be a breakthrough in finding new indications. For example, thalidomide, the protagonist of the drug damage event that caused numerous "seal babies" deformed infants, was found to be due to the degradation of a transcription factor - SALL4 after delisting, which made thalidomide have a new clinical application. In 1998, it was approved by FDA for the treatment of leprosy nodular erythema, and in 2006, it was approved for the treatment of multiple myeloma. ADR study of delisted drugs can not only avoid the loss of drug development in advance but also bring hope to new indications.

MCE has sorted out 211 drug compounds withdrawn from the market through FDA, EMA and other authoritative platforms. Each compound has withdrawal records in at least one country/market. It is a useful tool for conducting research on drug side effects or drug toxicity mechanisms and discovering new indications of drugs.

Copper is an important co-factor of all biological enzymes, but if the concentration exceeds the threshold of maintaining the homeostasis mechanism, copper will lead to cytotoxicity. This death mechanism has been named "Cuproptosis".

The mechanism of cuproptosis distinct from all other known mechanisms of regulated cell death, including apoptosis, pyroptosis, necroptosis, and ferroptosis.

Copper combine with the lipoylated components of the tricarboxylic acid cycle (TCA), leading to lipoylated protein aggregation and subsequent loss of iron-sulfur cluster proteins, ultimately resulting in protein toxicity stress and cell death. Studies have shown that the necessary factors for cuproptosis include the presence of glutathione, mitochondrial metabolism of galactose and pyruvate, and glutamine metabolism.

Targeted regulation of cuproptosis is a potential choice to treat cancer, rheumatoid arthritis, and other diseases. For example, up-regulation of LIPT1 may inhibit the occurrence and development of tumors by destroying TCA in mitochondria and then inducing cuproptosis.

MCE supplies a unique collection of 258 cuproptosis-related compounds, all of which act on the targets or signaling pathways related to cuproptosis and may have in inhibitory or activated effect on cuproptosis. MCE Cuproptosis Library is a useful tool for drug research related to cancer, rheumatoid arthritis, and other diseases.

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 117 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

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

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

MCE supplies a unique collection of 68 compounds related to the TCA cycle. MCE TCA Cycle Compound Library is a useful tool for the TCA cycle related research and anti-cancer drug development.

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 708 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.

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 5,189 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

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 131 liposome compounds, which is a good tool for lipidomic-related studies.

Mitochondrial autophagy refers to the selective encapsulation and degradation of damaged mitochondria by cells through the autophagy mechanism, thereby maintaining mitochondrial and cellular homeostasis. The concept of mitochondrial autophagy has received extensive attention since it was proposed. Current studies have shown that the mechanisms of mitochondrial autophagy can generally be divided into two categories: Ubiquitin-dependent pathways and Ub-independent pathways. In addition, mitochondrial autophagy is a research hotspot related to the pathogenesis of neurodegenerative diseases, cardiovascular diseases, cancer, metabolic diseases and other clinical diseases. Therefore, high-throughput screening based on mitochondrial autophagy can effectively screen out compounds that are closely related to the occurrence of diseases and analyze their mechanisms.

MCE can provide a library of 713 mitophagy compounds, which can be used for drug development and mechanism research in cancer, immunity, infection and other hot research fields.

Increasing research have shown that Traditional Chinese Medicine (TCM) possess antiviral activities against various viral strains, such as herpes simplex virus, influenza virus, hepatitis B and C viruses, and SARS-CoV. To date, dozens of Chinese herbs and hundreds of natural TCM ingredients have been reported to exhibit good antiviral activities. Active components from TCM are one of the important sources for antiviral drugs discovery.

MCE designs a unique collection of 173 active compounds of antiviral Chinese Herbal Medicines. MCE Antiviral Traditional Chinese Medicine Active Compound Library is a useful tool for discovery antiviral drugs from TCM.

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 1,655 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.

Natural products are characterized by enormous scaffold diversity and structural complexity, because of which, natural products do show a wide range of biological activities. Medicinal plants have been the major source of medicines over many centuries. About a quarter of all Food and Drug Administration (FDA) and/or the European Medical Agency (EMA) approved drugs are plant based, with well-known drugs such as Paclitaxel and Aspirin having been isolated from plants.

MCE provides a unique collection of 2,933 plant-sourced natural products. MCE Plant-Sourced Natural Product Library is a useful tool for drug discovery that can be used for high throughput screening (HTS) and high content screening (HCS).

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 288 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.

Depression is a serious global affective disorder and one of the most common neurological diseases whose clinical manifestations are low mood, loss of interest, anhedonia, loss of energy, and fatigue, people with major depressive disorder (MDD) can even have suicidal thoughts and behaviors.

Currently available antidepressants have significant limitations, including a long time lag for a therapeutic response (weeks to months) and low response rates. This is particularly problematic for a disease with a high suicide rate. Therefore, the development of new antidepressant drugs is particularly urgent.

MCE offers a unique collection of 2,029 compounds with antidepressant activities or targeting the unique targets of depression. MCE Antidepressant Compound Library is a useful tool for exploring the mechanism of depression and discovering new drugs for depression.

Protein protein interactions (PPI) have pivotal roles in life processes. The studies showed that aberrant PPI are associated with various diseases, including cancer, infectious diseases, and neurodegenerative diseases. The classic drug targets are usually enzymes, ion channels, or receptors, the PPI indicate new potential therapeutic targets. Therefore, targeting PPI is a new direction in treating diseases and an essential strategy for the development of new drugs.

However, the design of modulators targeting PPI still faces tremendous challenges, such the difficult PPI interfaces for the drug design, lack of ligands reference, lack of guidance rules for the PPI modulators development and high-resolution PPI proteins structures.

With the development of high-throughput technology, high-throughput screening is also gradually used for the identification of PPI inhibitors, but the compound library used for conventional target screening is not very effective in screening PPI inhibitors. To improve screening efficiency, MCE carefully selected 656 PPI inhibitors and mainly targeting MDM2-p53, Keap1-Nrf2, PD-1/PD-L1, Myc-Max, etc. MCE Protein-protein Interaction Inhibitor Library is a useful tool for PPI drug discovery and related research.

Natural product have great diversity and structural complexity of scaffolds. And the number of their drugs represents a large number of sources of new pharmacological entities, so natural products are of great significance in drug discovery. The Dictionary of Natural Products (DNP) shows that natural products mainly come from plants, animals and microorganisms, and animal sources are the second important source of natural products. Animal derived natural products exist to varying degrees in almost all forms of animals, generally secondary metabolite extracted from organisms.

MCE provides a unique collection of 1,056 animal-sourced natural products. MCE Animal-Sourced Natural Product Library is a useful tool for drug discovery that can be used for high throughput screening (HTS) and high content screening (HCS).

Pesticide is a single substance or mixture that can be used to prevent, mitigate, iminate pests or as a plant conditioner, defoliant or desiccant. In recent years, scientists have proposed the concept of "Molecules to Ecosystems", bringing the concept of molecular biology to understand the impact of pesticides, degradation and relationship with the environment or organisms. MCE integrates effective compounds approved as pesticides by agencies such as the Environmental Protection Agency (EPA) and some insecticidal compounds with potential for agricultural applications.

MCE can provide a library of 293 pesticide compounds that are tool compounds for relevant research.

Rheumatoid Arthritis (RA) is a autoimmune disease characterized by persistent joint inflammation. The pathology of RA includes immune cell infiltration, synovial lining proliferation, pannus formation, and the destruction of joint cartilage and bone, which is highly disabling. Due to long-term chronic inflammation, RA not only severely affects the quality of life of patients but can also damage multiple organs, leading to lung diseases, cardiovascular diseases, and malignant tumors. The pathogenesis of RA is complex, involving genetic, environmental, and immune factors. With the advancement of high-throughput screening technology, screening for compounds targeting JAK, CCR, MEK, MMP targets may contribute to the development of more effective drugs against Rheumatoid Arthritis (RA).

MCE has collected 1,483 small molecule compounds with definite or potential anti-rheumatoid arthritis activity. This library is of significant value for researching the anti-RA drugs.

Vitamins are a category of trace organic compounds essential for maintaining normal physiological functions in living organisms. They are classified into fat-soluble and water-soluble vitamins. Fat-soluble vitamins play a role in maintaining vision, bone health, reproductive functions, and blood coagulation. Water-soluble vitamins are involved in energy metabolism, nervous system function, and cellular repair processes. Most vitamins cannot be synthesized by the organism and must be obtained through diet. In recent years, vitamins and their derivatives have become increasingly important in the field of drug development due to their extensive physiological activities. Additionally, vitamins and their derivatives can be used to construct research platforms for vitamin metabolism, which helps to delve into the metabolic pathways and dynamic changes of vitamins within the body and aids in identifying new biomarkers for certain diseases.

MCE included 142 vitamins and their derivatives, including Vitamin A, Vitamin B, Vitamin D, etc., which is a good tool for studying vitamin metabolism.

Chemotherapy is one of the most common treatments for cancer. It can be used alone for some types of cancer or in combination with other treatments such as radiation or surgery. Chemotherapy drugs usually target cells at different phases of the cell cycle and inhibit tumor proliferation and avoid cancer cell invasion and metastasis. It is a cancer treatment method that kills cancer cells with drugs.

Chemotherapeutic agents can be classified into alkylating agents, antimetabolites, antimicrotubular agents, antibiotics, etc. according to the mechanism of action. MCE offers a unique collection of 153 chemotherapy drugs, which is a useful tool for cancer treatment research.

Pain is a kind of distressing feeling caused by the stimulation of tissue damage. According to the International Association for the Study of Pain (IASP), pain is defined as ”An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage”.

Pain is usually classified according to its location, duration, underlying causes, and intensity. For example, acute and chronic pain, muscle pain, and nerve pain. Pain is the main symptom of most diseases, which seriously affects the quality of life and body function of patients. In the medical treatment of pain, anti-inflammatory drugs and opioid analgesic agents have traditionally been used, but the side effects are serious. In recent years, targeted drugs targeting the ERK/MAPK pathway or other targets have gradually become a research hotspot.

MCE supplies a unique collection of 2,354 compounds targeting key proteins in the pain system. MCE Pain-Related Compound Library is a useful tool for pain related research and anti-pain drug development.

Neurotransmitters are chemical messengers that allows a neuron's electrical signal to pass to a postsynaptic neuron or effect target. Neurotransmitters include amino acids, monoamines, and peptides, while other neurotransmitters are composed of metabolites such as nitric oxide and carbon monoxide. The function of neurotransmitters is closely related to the disease of life, helping to regulate the body's heartbeat, blood pressure, breathing, sleep, aging and muscle activity. Therefore, research based on neurotransmitters can help to increase human understanding of diseases.

MCE collects and organizes 56 neurotransmitters and is a tool library for drug screening and mechanism research.