core structural

Cysteine proteases (CPs), a key enzyme family regulating physiological metabolism and mediating pathological processes (e.g., abnormal bone resorption, tumour invasion, and pathogen infection), represent a core therapeutic target for disease intervention via the development of specific inhibitors. Currently reported CP covalent inhibitors encompass diverse structural types, including epoxides, aziridine, and activated double bonds (vinyl sulphones, α,β-unsaturated ketones), providing clear structural references for the development of novel CP covalent inhibitors.

This compound library contains multiple warheads that specifically target cysteine proteases, serving as a powerful tool for the efficient discovery of novel covalent inhibitors against this enzyme family.

Natural products are an attractive source with varied structures that exhibit potent biological activities, and desirable pharmacological profiles. The core scaffold of a natural product can also provide a biologically validated framework upon which to display diverse functional groups. Inspired by bioactive natural products, natural product-like compounds, occupying the same chemical space, are ideally suited to explore and to facilitate understanding of biological pathways.

MCE provides a unique collection of 15,445 natural product-like compounds that are structurally like Steroids, Tannins, Flavonoids, Quinones, Isoquinolines, etc. This library is an important source of lead compounds for drug discovery.

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.

The rising prevalence of multidrug-resistant and extensively drug-resistant bacteria, combined with emerging resistance mechanisms and the limitations of existing antibacterial drugs, creates an urgent need for novel antibacterial agents. Antibacterial compound libraries serve as key tools to support antibacterial drug screening and development.

This library features structurally diverse compounds, including small-molecule scaffolds and natural product derivatives, and exhibits diverse antibacterial mechanisms of action. For example, these compounds exert antibacterial effects by disrupting bacterial cell structures, interfering with bacterial metabolic processes, and inhibiting nucleic acid synthesis. The derivation of scaffold structures enhances their activity against drug-resistant bacteria and their selectivity against different types of bacteria. This library can be used for the high-throughput screening of novel antibacterial drug candidates and the identification of potent compounds against drug-resistant and multidrug-resistant bacteria. Additionally, it provides a reference for compound structural modification, enabling further in-depth research on the structure-activity relationships(SARs) of antibacterial drugs. It can also be applied to the exploration of bacterial resistance mechanisms and reversal strategies, as well as the discovery of antibacterial molecules that inhibit efflux pumps and restore drug susceptibility.

The library contains 10855 structurally diverse drug-like compounds. Its core compound sources include analogs of known antifungal active moleculeswith a similarity score of ≥ 0.6. MCE has collected more than 1900 antibacterial molecules. All screened compounds conform to lead-like physicochemical properties, providing valuable support for the research and development of novel antibacterial drugs.

Quinone compounds are a significant class of natural products featuring a conjugated quinone structure, widely distributed in plants, fungi, and microorganisms. Based on their core structures, they can be primarily categorized into benzoquinones, naphthoquinones, phenanthrenequinones, and anthraquinones, among others. This structural diversity endows quinone compounds with a broad spectrum of pharmacological activities, making them key components in traditional Chinese medicine (such as rhubarb, Lithospermum erythrorhizon, and Salvia miltiorrhiza). Modern research has confirmed that their activities encompass anti-tumor, anti-inflammatory, antibacterial, antiviral, antiplatelet aggregation, and neuroprotective effects, among others, establishing them as an important source for drug development.

MCE designs a unique collection of 95 quinones that all come from natural products. MCE Quinones Library is a useful tool for drug discovery that can be used for high throughput screening (HTS) and high content screening (HCS).

MCE-18 stands for Medicinal Chemistry Evolution 2018, which was first published in Journal of Medicinal Chemistry in 2019 for assessing molecular novelty and three-dimensional complexity. Developed based on Clarivate global pharmaceutical patent database, this descriptor was constructed via big-data analysis covering 28,161 patented lead compounds, 1,370 approved drugs and nearly 30,000 preclinical-to-phase III drug candidates from 23 top pharmaceutical companies worldwide between 1950 and 2018, followed by structural clustering and removal of redundant outdated scaffolds for data denoising. Its scoring system integrates five core structural features including aromatic ring (AR), aliphatic heterocycle (NAR), chiral center (CHIRAL), spiro atom (SPIRO), cyclic and acyclic sp³ carbon ratio together with a quadratic topological correction factor. Breaking the limitations of the single Fsp³ parameter, MCE-18 effectively distinguishes conventional flat aromatic scaffolds from modern 3D-enriched novel chemotypes, overcoming typical drawbacks of traditional compound libraries such as scaffold redundancy, low screening hit rates and poor compatibility with allosteric and PPI-related difficult targets.

This library contains over 37,000 structurally diverse compounds with favorable overall drug-likeness, suitable for high-throughput screening against canonical targets including kinases, GPCRs and proteases as well as challenging allosteric and PPI targets. Compounds comply with the developmental trend of modern novel drug discovery, supporting routine primary screening as well as early hit identification of allosteric modulators and PPI inhibitors, serving as an efficient screening resource for early-stage innovative drug discovery.