surface

RNA is crucial for the regulation of numerous cellular processes and functions. With the in-depth study of disease mechanisms, processes such as RNA expression, splicing, translation, and stability regulation have become new targets for disease intervention. RNA has provided new therapeutic modalities for metabolic diseases, genetic disorders, and cancer patients, resulting in several innovative drugs.

MCE R&D team collected small molecules targeting RNA from the PDB, R-BIND, ROBIN, and internal database as the positive dataset, and non-targeting RNA small molecules from ROBIN as the negative dataset. Based on the GeminiMol pre-trained model, we encoded the molecules and calculated over 1700 molecular descriptors using Mordred as inputs for the model. Subsequently, we employed 13 deep learning models to learn from the data. All of which yielded good training results, with AUROCs greater than 0.75. Ultimately, we selected the Finetune model to screen HY-L901P, which exhibited the best classification performance, achieving an AUROC of 0.82 and a prediction accuracy of 0.76. We then applied filtering based on StaR rules (with at least two of the following properties: cLogP ≥ 1.5, Molar Refractivity ≥ 4, Relative Polar Surface Area ≤ 0.3) to obtain a library containing approximately 5,000 small molecule compounds targeting RNA. This library serves as a valuable tool for screening small molecules that interact with RNA.

Chemokines, or chemotactic cytokines, are small cytokines or signaling proteins secreted by cells. They are a component of intercellular communication, controlling the directional movement of immune cells especially leukocytes, as well as other cell types, for instance, endothelial and epithelial cells, which are essential to maintain human health and the function of the immune system.

The biological effects of chemokines are achieved by binding to chemokine receptors, which are G protein-coupled receptors found on the surface of leukocytes. Some chemokine receptors are involved in directing tumor metastasis and over-expression by certain tumors. So inhibiting the interaction between chemokine and chemokine receptors on the surface of tumor cells may be a new possible therapeutic approach. Some chemokine receptors are coreceptors for HIV entry, and related inhibitors have been approved by the FDA to treat patients with HIV. Obviously, chemokines and chemokine receptors have become new targets for studying cancer, HIV, inflammation, and other diseases.

MCE supplies a unique collection of 237 chemokine or chemokine receptor inhibitors and activators, all of which have the identified inhibitory or activated effect on chemokine or chemokine receptors. MCE Chemokine Library is a useful tool for drug research related to cancer, AIDS, and wound therapy.

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 3,350 small molecules targeting GPCRs that can be used in the screening for various GPCRs-related research and drug development projects.

Molecular Glue Virtual Library is constructed using generative AI technology, integrating the structural features, activity data of known molecular glues, and interaction information of ternary complexes (target protein-E3-molecular glue). Endowed with structural novelty, drug-likeness, diversity and synthesizability, it is applicable to molecular glue-based AI drug screening and large-scale virtual screening.

MCE builds this library based on high-quality molecular building blocks by virtue of robust computing power, coupled with rigorous reaction rules and optimized compound generation strategies. To ensure library quality, molecules with high synthetic difficulty, poor drug-likeness, PAINS and other undesirable molecules are excluded first. Subsequently, scaffold-based compound analysis is performed to screen drug-like diverse molecules for synthesizability evaluation; those with excessively high synthetic difficulty are removed, ultimately forming a large-scale molecular glue virtual library with structural diversity, synthesizability and drug-likeness.

Compounds in the library can be synthesized in only 1-2 chemical reaction steps. With MCE’s experienced chemical synthesis team, custom synthesis of different scales from milligram to kilogram can be easily achieved to meet diverse customer needs.

Membrane receptors, also known cell surface receptors or transmembrane receptors, are transmembrane proteins embedded into the plasma membrane which play an essential role in maintaining communication between the internal processes within the cell and various types of extracellular signals. They act in cell signaling by receiving (binding to) extracellular molecules, which are also called ligands. These extracellular molecules include hormones, cytokines, growth factors, neurotransmitters, lipophilic signaling molecules such as prostaglandins, and cell recognition molecules.

There are three kinds of membrane receptors: ion channel-linked receptors, enzyme-linked receptors and G-protein-linked receptors. They play important roles in keeping human normal physiologic processes. GPCRs and ion channels are important drug targets in drug discovery.

MCE provides a unique collection of 6,775 compounds targeting a variety of membrane receptors. MCE Membrane reeptor-targeted Compound Library can be used for membrane receptor-focused screening and 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 943 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.

A parasite is an organism that lives on or in a host organism and gets its food from or at the expense of its host. Parasites of humans include protozoans, helminths, and ecto-parasites (organisms that live on the external surface of a host). They are responsible for many diseases and are transmitted to their hosts most often through the ingestion of contaminated food, water or through the bite of an arthropod (e.g., a fly or tick), which can act as an intermediate host and as a vector. Parasitic diseases of humans are a major global health problem causing significant morbidity and mortality, especially in developing countries. Each year there are hundreds of millions of people infected with disease-causing parasites, particularly in tropical and subtropical regions of the world, resulting in an estimated one million deaths. Therefore, there is a dire need of novel anti-parasitic drugs.

MCE has a unique collection of 637 compounds with validated anti-parasitic activity which offer researchers an opportunity to screen novel anti-parasitic targets.

Hormones are a class of biologically active substances secreted by endocrine gland cells, which are transported through the circulatory system to various parts of the body, and precisely act on specific target organs or cells, playing a crucial role in regulating the growth, development, metabolism, and reproduction of organisms. The mechanisms of hormone action are diverse and complex. Some hormones (such as corticosteroids, vitamin D, and thyroid hormones) can enter the cell interior and interact with receptors in the nucleus, thereby regulating gene expression and affecting cell function. Other hormones (such as growth hormone and thyrotropin-releasing hormone) bind directly to receptors on the cell surface, exerting their effects by regulating enzyme activity or influencing the state of ion channels. Additionally, hormones play a key role in the study of endocrine and metabolic diseases, and are closely related to the development of diseases such as diabetes and thyroid diseases.

MCE has included 86 human hormone compounds, which is of great significance for the study of human metabolic pathways, and can also be used to build a metabonomics database.

Viruses are much simpler organisms than bacteria, and they are made from protein substances and nucleic acid. Despite the fact that the exact mechanism of infection is extremely specific to each type of virus, the general scheme of infection can be represented in the following manner: A virus is absorbed at the surface of a host cell and then permeates through the membrane, where it releases nucleic acid from its protein protection. Then the viral nucleic acid begins to replicate, and transcription of the viral genome takes place either in the cytoplasm, or in the nucleus of the host cell. As a result of these events, a large amount of viral nucleic acid and protein are made to make new generations of virions. Therefore, one mechanism of action of antiviral drugs is to interfere with the ability of a virus to get into a target cell. A second mechanism of action is to target the processes that synthesize virus components after a virus invades a cell, such as nucleotide or nucleoside analogs.

MCE designs a unique collection of 1,168 anti-virus compounds that target several viruses, including SARS-CoV, HBV, HCV, HIV, HSV and Influenza Virus. It’s an effective tool for anti-virus drug discovery.

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

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

MCE offers a unique collection of 61 marine-sourced natural products which can be used for drug discovery for high throughput screening (HTS) and high content screening (HCS). MCE marine-sourced natural product library is an important source for drug discovery and development.

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

In contrast to the high conservation of conventional orthosteric sites, allosteric sites possess structural characteristics of low conservation, high hydrophobicity, weak polarity, confined spatial geometry, and dynamic cryptic properties. There is a significant difference between their core structures and orthosteric pockets — allosteric pockets are mostly dynamic grooves formed by protein conformational changes, subunit interface clefts, or shallow depressions, rather than the rigid "keyhole" structure of orthosteric sites. With looser spatial constraints, allosteric sites have the advantages of high selectivity and low off-target risk, and have become an important direction in new drug discovery.

Based on the dynamic, hydrophobic, and narrow-long spatial characteristics of allosteric pockets, MCE has performed targeted modification and screening of fragments. The screening criteria strictly conform to the requirements of allosteric binding: molecular weight is controlled at 120–280 Da (to meet the core needs of small molecules in fragment libraries and high derivatization), hydrogen bond donors (HBD ≤ 2), hydrogen bond acceptors (HBA ≤ 3), polar surface area (PSA = 30–80 Ų), rotatable bonds (≤ 2), moderate hydrophobicity (cLogP = 1–3.5), no strongly ionizable groups, and both appropriate rigidity and conformational flexibility to adapt to the dynamic changes of the pocket. Meanwhile, combined with the results of principal moment of inertia (PMI) analysis, fragments with high 3D diversity were obtained. Such fragments have good shape complementarity with allosteric pockets, ensuring that the fragments can smoothly enter the allosteric pockets and form stable binding, while providing room for subsequent optimization and derivation.

This library contains 1,800 structurally diverse fragment molecules with excellent drug-like properties, suitable for allosteric drug development and the design and optimization of allosteric sites. It combines the