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Protein protein interactions (PPI) have pivotal roles in life processes. The studies showed that aberrant PPI are associated with various diseases. 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.

The PPI Library comprises molecules of various sizes, frameworks, and shapes ranging from fragment-like entities to macrocyclic derivatives designed as secondary structure mimetics or as epitope mimetics. The designs cover β-turn / loop mimetics and α-helix mimetics. Since helices present at the interface in 62% of all protein-protein interactions. This library focused on designs including mimics with the substitution geometry of an a-helices, as well as designs that mimic the location of “hot-spot” side chains in helix-mediated PPIs.

Cysteine proteases (CPs), a key enzyme family regulating physiological metabolism and mediating pathological processes (such as abnormal bone resorption, tumour invasion, and pathogen infection), represent a core therapeutic target for developing specific inhibitors in disease intervention. Currently reported CP inhibitors primarily achieve their inhibitory function by precisely binding to CP active pockets (e.g., S1-S4 non-primed regions or S1'-S2' primed regions) and forming covalent/non-covalent interactions with the active site cysteine residues, providing clear structural references for the development of novel inhibitors.

This compound library, designed based on the core strategy of "similarity-based known active structures", contains over 200 cysteine protease inhibitors. Leveraging AI-driven molecular screening technology, it retains the critical pharmacological and shape features of reported CP inhibitors, serving as a specialized tool for efficiently discovering novel cysteine protease inhibitors.

Fragment-based drug discovery (FBDD) is well suited for discovering both drug leads and chemical probes of protein function. 3-dimensionality (3D) diversity is pivotal because the molecular shape is one of the most important factors in molecular recognition by a biomolecule. There is a developing appreciation that 3D fragments could offer opportunities that are not provided by 2D fragments.

MCE 3D Diverse Fragment Library consists of 5,400 non-flat fragment-like molecules (average Fsp3 value 0.58). More than 4,700 fragment compounds contain at least one chiral center in the structure. The key concepts that underlie the library design were 3D shape, structural diversity, reactive functionality and fragment-like. This 3D Diverse Fragment Library brings higher fragment hit optimization and increases the likelihood to find innovative hits in FBDD.

Cosmetics are complex mixtures formulated through the rational blending and processing of various natural, synthetic, or extracted raw materials. The ingredients used in cosmetics are diverse in type and functionality. Based on their properties and applications, cosmetic ingredients can generally be classified into two main categories: base materials and auxiliary ingredients. The former constitutes the primary component of cosmetics, accounting for a significant proportion in formulations and serving as the key functional substances. Auxiliary ingredients, on the other hand, play roles in shaping the product, ensuring stability, or imparting color, fragrance, and other specific characteristics.Establishing a systematic ingredient database is of great significance for cosmetic research and development. By analyzing the physicochemical properties (such as oil-water partition coefficients and molecular weight distribution), biological activity mechanisms (such as antioxidant pathways and cellular signaling regulation), and compatibility of ingredients, the database can provide precise guidance for formulation design. This approach helps shorten the development cycle of cosmetic/skincare products and reduces trial-and-error costs.

MCE offers 622 types of cosmetic ingredient compounds, including antioxidants, humectants, emulsifiers, film-forming agents, and more.

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

Owing to the high conservation of orthosteric sites, conventional orthosteric drugs frequently suffer from poor subtype selectivity, off-target toxicity, and drug resistance, severely restricting their clinical application. In contrast, allosteric sites feature low conservation, high hydrophobicity, weak polarity, confined spatial geometry, and dynamic cryptic properties. These characteristics endow allosteric modulators with distinct advantages including high selectivity, functional tunability, and improved safety, making allosteric therapy a key direction in modern drug discovery.

MCE has curated nearly 1,000 structurally disclosed clinical-stage allosteric modulators. By analyzing allosteric protein–ligand complex structures from the PDB database, we extracted core pharmacophores and privileged scaffolds. Adopting a rational design strategy of “scaffold derivation + allosteric physicochemical filtering”, we performed secondary screening on the derived compounds strictly following the optimal physicochemical principles for allosteric binding based on universal allosteric pocket properties: molecular weight 300–500 Da, HBD ≤ 3, HBA = 3–8, PSA = 70–120 Ų, rotatable bonds ≤ 6, highly rigid scaffolds, cLogP = 1.0–3.8, and no strongly ionizable groups. The selected compounds exhibit high rigidity and shape complementarity, making them well-suited for targeting shallow, dynamic, and hydrophobic-dominated allosteric pockets.

This allosteric modulator library contains 4,315 structurally diverse, lead-like compounds dedicated to allosteric drug development, allosteric site targeting, and allosteric modulator screening. It is suitable for kinases, GPCRs, and other important drug targets. All compounds are analogs of clinical-stage allosteric modulators with a similarity score > 0.6, combining excellent druggability and allosteric binding potential. It provides a highly efficient tool for early-stage allosteric drug discovery.