Cancer

Tonifying traditional Chinese medicines occupy a central position in the traditional medical system, with their core value lying in the regulation of the body's functional state. Modern pharmacological studies have confirmed that these medicinal materials and their monomeric components possess multiple biological activities, including bidirectional immune regulation, anti-aging and lifespan extension, neuroprotection and cognitive enhancement, as well as hematopoietic and metabolic regulation. According to the traditional Chinese medicine theory of “strengthening the body’s resistance and consolidating the foundation”, tonifying medicines are mainly classified into four major categories: Qi-tonifying, Blood-tonifying, Yin-tonifying, and Yang-tonifying. This compound library strictly follows this classification system for compound collection.

Monomeric compounds derived from traditional Chinese medicines demonstrate excellent drug-like properties. They naturally possess structural diversity and clearly defined pharmacological activities, which help improve screening success rates and make them ideal tools for studying multi-target synergistic effects. This library contains 1,039 compounds, providing a material basis for investigating synergistic interactions among compounds (network pharmacology) and facilitating the development of multi-target therapeutic strategies for complex diseases such as cancer, neurodegenerative disorders, and metabolic syndrome.

PD-1/PD-L1 are key immune checkpoint targets that suppress T-cell-mediated anti-tumor immunity, representing a major focus in cancer immunotherapy. While antibody drugs dominate the clinic, they are limited by administration challenges and immune-related side effects. Small-molecule PD-1/PD-L1 inhibitors, with oral availability, good tissue penetration and low cost, have emerged as a promising next-generation strategy.

A PD-1/PD-L1 lead-like library was built via a five-step virtual screening process. After collecting 8,947 inhibitors from BindingDB and PubChem and filtering by activity and duplicates, AI similarity screening was performed using GeminiMol. Key pharmacophores were extracted from the PPI interface of co-crystal structures, and molecular was screened via a pharmacophore model, effectively enhancing target activity.

Containing 10,000 structurally diverse and drug-like molecules well-matched to the PD-L1 pocket, the library supports virtual docking, high-throughput screening and hit discovery, enabling efficient and rapid development of small-molecule immunotherapies.

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 826 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.

Seven-membered rings are privileged medium-sized scaffolds with distinct twist-chair conformations and greater 3D diversity than five- and six-membered rings. Their flexible conformations allow induced-fit protein binding and precise pharmacophore positioning. They also modulate Fsp³, pKa and logP to enhance solubility and permeability. Azepanes, oxepanes and benzodiazepines serve as bioisosteres for hit discovery against GPCRs, ion channels and kinases.

Widely found in plant and microbial alkaloids, seven-membered heterocycles show excellent biocompatibility and target affinity. They underpin many approved drugs for CNS, cancer and infectious diseases, including diazepam, imipramine and carbamazepine. Clinical candidates further highlight their unique value. However, high transannular strain and synthetic difficulty limit their availability, leaving them rare in standard screening libraries.

MCE 7 Membered Scaffold Library contains 2,792 structurally diverse, lead-like molecules covering azepanes, oxepanes, benzodiazepines and dibenzazepines. With varied substitutions, chiral centers and synthetic accessibility, it fills the shortage of medium-ring scaffolds. Ideal for HTS, virtual screening and SAR studies, these novel, patent-clear compounds offer a distinctive starting point for drug discovery in CNS disorders, oncology, antivirals and challenging targets such as PPIs.

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 458 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.

Boronic acid and boronic ester represent a relatively novel and promising chemical structure in drug design. Boronic acid exists in an sp²-hybridized state, possessing an empty p-orbital that can act as a Lewis acid to accept lone pairs from heteroatoms (O, N, or S). This Lewis acidity enables it to form reversible covalent bonds with amino acid residues such as lysine, serine, threonine, and histidine. Currently, five FDA-approved drugs containing boronic acid or boronic ester predominantly involve such covalent binding mechanisms in their interactions with target proteins. Furthermore, boronic acid can serve as a bioisostere for carboxylic acids, phosphates, and phenolic groups, utilized to improve pharmacokinetic properties and enhance drug efficacy.

To date, five boron-containing drugs have been approved by the FDA. The unique properties of boronic acids and boronic esters confer significant potential in drug design, with applications spanning cancer therapy (e.g., multiple myeloma), anti-infectives (e.g., fungal infections, tuberculosis), anti-inflammatory treatments (e.g., atopic dermatitis), antibacterial agents (e.g., carbapenem-resistant bacterial infections), and Reactive Oxygen Species (ROS)-responsive prodrugs, among others. The MCE Boronic Acid/Boronic Ester Fragment Library, which contains 1,488 compounds, serves as a valuable tool for the development of boron-containing drugs.

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.

Ion channels are key proteins on the cell membrane that regulate the flow of ions across membranes. They participate in nearly all physiological processes, including nerve conduction, muscle contraction, heart rhythm, and pain perception. Abnormalities in their function can lead to various serious diseases such as arrhythmia, epilepsy, hypertension, neuropathic pain, and cancer. Therefore, ion channels are highly valuable drug targets—over 15% of approved drugs target ion channels currently, demonstrating their irreplaceable therapeutic value in cardiovascular, neurological, and analgesic fields.

MCE has collected a library of over 5,000 reported ion channel-related bioactive compounds targeting major sites such as Na+ channels, K+ channels, Ca2+ channels, GABA receptors, iGluRs, and others. Using AI models, these compounds are characterized through both 2D representations (molecular fingerprints, pharmacophores) and 3D representations (3D conformation) to screen for a collection of lead-like compounds highly similar to known active molecules. Additionally, an hERG channel prediction algorithm integrating XGB and ISE mapping strategy is employed to assess and exclude potential cardiotoxicity in the library.. This step significantly reduces safety risks in subsequent screenings, particularly for ion channel drug development related to cardiovascular systems (e.g., Nav1.5, Cav1.2), effectively minimizing failures due to hERG inhibition and serving as a valuable tool for ion channel drug screening.

POI (Protein of Interest) refers to the target protein, namely the disease-causing protein or key functional protein that undergoes degradation or functional modulation in molecular glue-mediated processes. The Molecular Glue POI Library consists of a series of fragments that can specifically bind to different types of POIs. As key components of molecular glues, these ligands form stable interactions with target proteins, laying the foundation for molecular glues to induce the interaction between POIs and E3 ubiquitin ligases. The covered POIs include various types such as cancer-associated GSPT1, androgen receptors, and abnormally aggregated proteins linked to neurodegenerative diseases.

This fragment library can be applied to the screening and optimization of targeted protein degraders. By screening ligands with high affinity and strong selectivity for specific POIs from the library, core structures can be identified to develop novel molecular glues. For instance, optimization of ligands targeting GSPT1 has yielded molecular glue degraders with enhanced degradation activity. Since many POIs are difficult to drug due to the lack of traditional small-molecule binding pockets, some ligands in the POI Ligand Library can modulate such POIs by inducing protein-protein interactions, thereby further expanding the scope of drug discovery for undruggable targets.

MCE has compiled a POI Fragment Library comprising thousands of POI fragments with molecular weights ranging from 150 to 400. This compound library can be widely applied in Molecular Glue research and development.

Carbohydrate metabolism serves as a central hub for energy supply and biosynthesis in living organisms and plays a critical role in the onset and progression of various diseases. In recent years, studies have shown that tumor cells reprogram their energy metabolism through aerobic glycolysis (the Warburg effect) to support rapid proliferation. Immune cells also rely on specific carbohydrate metabolic pathways to regulate their activation and differentiation states, while disorders such as diabetes and metabolic syndrome arise directly from dysregulation of carbohydrate metabolism. In addition, enzymes and key metabolic nodes involved in carbohydrate metabolism have become important targets for drug discovery, and therapeutic strategies targeting glycolysis, the pentose phosphate pathway, and energy metabolism are continuously advancing the treatment of cancer and metabolic diseases. Therefore, systematic analysis of carbohydrate metabolic networks and their associated metabolites is of great significance for elucidating disease mechanisms and developing novel therapeutic approaches.

The MCE Carbohydrate Metabolism Metabolite Library is constructed based on classical carbohydrate metabolic pathways and contains 76 metabolites. It systematically integrates key metabolic networks, including glycolysis, the pentose phosphate pathway, the tricarboxylic acid (TCA) cycle, monosaccharide metabolism, and sugar acid interconversions. The library comprehensively covers core metabolic nodes from glucose uptake and utilization to energy production and biosynthesis, while also incorporating important upstream and downstream intermediates. It enables accurate representation of intracellular metabolic flux dynamics and is well suited for applications such as metabolic flux analysis, target validation, and mechanistic studies. Furthermore, it provides robust support for multi-omics integration and the development of precision intervention strategies.

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 394 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.