Rational design

Spirocyclic compounds, with rigid 3D structures, high Fsp³ and strong conformational restriction, are highly privileged scaffolds in small-molecule drug screening. They overcome drawbacks of planar aromatic compounds such as poor solubility, high off-target risks and weak druggability. Their orthogonal bicyclic geometry fits well into protein pockets, improving target affinity, subtype selectivity, metabolic stability and membrane permeability, making them ideal for hit identification against kinases, GPCRs, PPIs and other targets.

Spirocyclic scaffolds have been widely applied in oncology, antivirals, hypertension and CNS diseases, leading to many approved drugs and clinical candidates. SAR studies show that spiro-atom chirality, ring size and heteroatom substitution dominate bioactivity and selectivity, with the scaffold mainly serving as a conformational anchor. Azaspirocycles, spirooxindoles and spirosteranes target GPCRs, kinases, MDM2-p53 and PPIs. Approved drugs including irbesartan, spironolactone and rolapitant confirm their druggability, while revumenib and SAR405838 show promise against undruggable targets.

The MCE Spirocyclic Druglike Library contains over 1,000 diverse, stereospecific molecules selected by Lipinski’s rules. It covers privileged cores such as azaspirocycles, oxaspirocycles and spirooxindoles. These molecules bear rich chiral centers and distinct 3D orientations, reducing non-specific binding and enhancing screening efficiency. Featuring novel scaffolds, the library offers a highly innovative starting point for drug discovery.

Fragment-based drug discovery (FBDD) offers a strategic advantage by categorizing fragment hits according to their functional groups. This approach facilitates both the further optimization of these hits and the rational design of larger compounds through fragment combination. The amine functional group plays a vital role in drug development, as evidenced by its presence in many marketed drugs like Galantamine, Tacrine, and Rivastigmine. It is instrumental in enhancing solubility, improving bioavailability, and ensuring shelf-life stability—all critical factors for drug efficacy.

MCE offers a collection of 19,886 amine fragments for drug discovery. All of these compounds adhere to the Rule of Three (RO3) criteria for drug-likeness, which MCE offers a collection of 19,886 amine fragments for drug discovery, all of which stipulates a molecular weight ≤ 300 Da, ≤ 3 hydrogen bond donors, ≤ 3 hydrogen bond acceptors, and a cLogP ≤ 3.

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

Orthosteric sites are highly conserved, leading to poor subtype selectivity, off-target toxicity and drug resistance in traditional drugs. By contrast, allosteric sites show low conservation, high hydrophobicity, weak polarity, confined geometry and dynamic cryptic properties, granting modulators high selectivity, functional tunability and safety. Thus, allosteric therapy has become a major focus in drug discovery.

MCE curated nearly 1,000 clinical-stage allosteric modulators, analyzed PDB complex structures to identify key pharmacophores and privileged scaffolds, then designed and filtered compounds using rational “scaffold derivation + physicochemical screening” with strict property criteria. The resulting compounds show high rigidity and shape complementarity to shallow, dynamic, hydrophobic allosteric pockets.

This library comprises 4,315 diverse, lead-like compounds ideal for allosteric drug discovery and target screening, covering kinases, GPCRs and more. All are analogs of clinical-stage molecules with similarity > 0.6, combining high druggability and allosteric binding potential to support efficient early-stage R&D.