Construction of Inhibitor Libraries for Virtual Screening

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The successful discovery of enzyme inhibitors depends heavily on the quality and relevance of compound libraries. At Creative Enzymes, our Construction of Inhibitor Libraries for Virtual Screening service provides clients with carefully curated, customized, and scientifically validated libraries that serve as the backbone of effective screening campaigns. Our expertise in enzymology, cheminformatics, and drug design ensures that every library is optimally structured to maximize hit rates, minimize irrelevant compounds, and accelerate downstream inhibitor development. By combining pre-built repositories, commercial sources, and bespoke design strategies, we deliver libraries tailored to the unique needs of each client's research or industrial project.

Why Construct Inhibitor Libraries for Virtual Screening

Virtual screening has emerged as a powerful alternative to traditional high-throughput experimental methods, offering cost savings and speed without compromising accuracy. However, the effectiveness of virtual screening is fundamentally dependent on the quality of the compound libraries used. Poorly designed or unfocused libraries can lead to false positives, low hit rates, and wasted resources.

Enzyme inhibitors, in particular, present a unique challenge due to their structural diversity, specific binding requirements, and variable enzyme mechanisms. Libraries used for inhibitor discovery must therefore be diverse enough to capture a wide range of chemical scaffolds while still being focused enough to provide meaningful results against specific enzyme targets.

Construction of inhibitor libraries for enzyme virtual screening

Key Design Principles

Inhibitor library construction follows several strategic principles:

Target-Class Directed Design: Libraries are enriched with scaffolds known to interact with specific enzyme families (e.g., hinge-binding motifs for kinases)
Drug-Likeness Optimization: Application of filters for molecular weight (<500 Da), lipophilicity (Log P <5), hydrogen bond donors/acceptors, and rotatable bonds
Structural Diversity: Ensuring broad coverage of chemical space while maintaining focus on regions relevant to enzyme binding
Synthetic Accessibility: Prioritizing compounds that can be readily synthesized or purchased for experimental validation

Creative Enzymes has decades of experience in both enzyme research and inhibitor assays, allowing us to design libraries that balance breadth and specificity. With access to pre-built structural or activity-based libraries, alongside the ability to construct customized inhibitor sets, we provide comprehensive solutions that significantly enhance the reliability of virtual screening campaigns.

Our Service Offerings

Our Construction of Inhibitor Libraries for Virtual Screening service is designed to give clients an essential advantage in the discovery of enzyme inhibitors. We offer a flexible and comprehensive approach that includes:

Pre-Built Libraries: Large-scale repositories categorized by chemical frameworks, known activity profiles, or pharmacological relevance.
Custom Libraries: Tailor-made sets of compounds designed specifically for the client's enzyme target, therapeutic area, or industrial application.
Focused Sub-Libraries: Smaller, highly curated groups of compounds enriched with structural features known to interact with a specific enzyme class.
Vendor Integration: Coordination with commercial compound suppliers to ensure libraries are up-to-date, accessible, and ready for computational or experimental screening.
Data-Driven Refinement: Incorporation of structural biology, ligand-based data, and cheminformatics algorithms to maximize chemical diversity while reducing redundancy.

Our libraries are not just collections of molecules—they are strategically designed research tools that increase the likelihood of identifying potent and selective enzyme inhibitors.

Service Details

Services	Details
Selection of Library Strategy	Based on the objectives, we recommend one of three approaches: Use of pre-built, validated libraries for rapid screening. Customization of existing libraries with enriched structural motifs. Full construction of a bespoke library tailored to unique project needs.
Data Gathering and Curation	We compile potential compounds from diverse sources, including academic repositories, commercial vendors, and proprietary databases. Each entry undergoes rigorous filtering to remove unsuitable or redundant compounds.
Chemical Diversity Analysis	Using cheminformatics methods such as clustering, principal component analysis (PCA), and scaffold mapping, we ensure that libraries cover broad chemical space while avoiding unnecessary duplication.
Property Filtering and Rule Application	Compounds are filtered based on physicochemical properties (e.g., Lipinski's Rule of Five, ADMET predictions) to ensure drug-likeness and bioavailability. Specialized filters may be applied depending on the enzyme target (e.g., avoiding reactive functional groups).
Enrichment with Known Actives	Libraries may be seeded with molecules known to have inhibitory activity against related enzymes, improving the probability of identifying hits.

Contact Our Team

Full-Service Virtual Screening of Enzyme Inhibitors

Our comprehensive service is designed to guide your enzyme inhibitor project from initial evaluation to lead optimization. Explore our specialized modules:

Step 1 workflow—technical consultation and initial evaluation for virtual screening of enzyme inhibitors

Technical Consultation and Initial Inhibitor Evaluation

Step 2 workflow—construction of inhibitor libraries for virtual screening of enzyme inhibitors

Construction of Inhibitor Libraries for Virtual Screening

Step 3 workflow—virtual screening and ranking of potential enzyme inhibitors

Virtual Screening and Ranking of Potential Enzyme Inhibitor

Step 4 workflow—follow-up studies for enzyme inhibitor development

Follow-Up Studies for Enzyme Inhibitor Development

Inquiry

Why Choose Creative Enzymes

Extensive Expertise in Enzymology

Decades of experience in enzyme assays and inhibitor studies ensure that our libraries are scientifically grounded and highly relevant.

Flexible Library Options

From broad pre-built libraries to bespoke custom designs, we offer solutions tailored to every research goal and budget.

Rigorous Quality Control

Every compound undergoes strict filtering for structural validity, drug-likeness, and chemical diversity, ensuring libraries are both robust and reliable.

Integration with Virtual Screening

Our libraries are designed specifically for compatibility with virtual screening workflows, guaranteeing seamless downstream application.

Access to Vast Databases

Partnerships with commercial vendors and academic repositories give clients access to millions of potential compounds, all curated and formatted for immediate use.

Proven Success Across Industries

Our libraries have supported projects in pharmaceuticals, food technology, agriculture, and chemical processing, demonstrating broad applicability.

Case Studies and Real-World Applications

Case 1: Discovery of New Nicotinamides as Apoptotic VEGFR-2 Inhibitors with Virtual Screening

A library of modified VEGFR-2 inhibitors was designed and evaluated using in silico docking, ADMET, and toxicity studies. Four compounds demonstrated high predicted affinity and favorable drug-likeness. These compounds were synthesized and tested in vitro for cytotoxicity against cancer cell lines and VEGFR-2 inhibition. Notably, compound D-1 exhibited nearly double cytotoxicity compared to sorafenib against HCT-116 cells, induced apoptosis via caspase-8 and BAX upregulation, Bcl-2 downregulation, and caused cell cycle arrest at pre-G1 and G2-M phases. Molecular docking confirmed stable interactions with VEGFR-2 active site residues, and 100 ns MD simulations validated compound stability, supporting D-1 as a promising VEGFR-2 inhibitor.

Discovery of new nicotinamides as apoptotic VEGFR-2 inhibitors with virtual screening Figure 1. Superimposition of the native ligand (green) and the obtained pose (red) of the same ligand onto the VEGFR-2 TK active pocket. (Yousef et al., 2022)

Case 2: Discovery of a Natural METTL3 Inhibitor

N6-Methyladenosine (m6A) is the most common mRNA modification in mammalian cells, catalyzed mainly by the METTL3-METTL14 complex. Given METTL3's critical role in cancer and viral infections, a screening library of 1,042 natural products was evaluated using docking-based high-throughput screening, in vitro methyltransferase inhibition assays, cellular assays, and molecular dynamics simulations. Quercetin was identified as a potent METTL3 inhibitor with an IC₅₀ of 2.73 μM, reducing m6A levels in pancreatic cancer cells and inhibiting tumor cell proliferation. Binding studies revealed stable interactions within METTL3's SAM-binding pocket. This study provides the first natural product-derived METTL3 inhibitor, supporting drug development efforts.

Table 1. The molecular docking score of the selected 14 compounds after virtual screening and the ligands of METTL3 SAM. (Du et al., 2022)

Virtual screening of natural products for discovering METTL3 small molecule inhibitors

FAQs About Virtual Screening and Inhibitor Library Construction Services

Q: Why is library construction critical for virtual screening?

A: The quality of the compound library directly determines the success of virtual screening. A poorly designed library can waste resources, while a focused and diverse library increases the probability of identifying potent inhibitors.
Q: What types of libraries can you provide?

A: We offer pre-built, custom, and focused libraries, depending on client needs. Libraries may be categorized by structure, activity, enzyme class, or pharmacological relevance.
Q: Can you design libraries for enzymes with little or no structural data?

A: Yes. In such cases, we rely on ligand-based approaches and incorporate compounds with known inhibitory activity against related enzymes to build effective libraries.
Q: How large are the libraries you construct?

A: Libraries can range from a few hundred compounds for focused projects to millions for exploratory campaigns. The size is determined based on project scope, computational resources, and client requirements.
Q: How do you ensure libraries are "drug-like"?

A: Compounds are filtered using established drug-likeness criteria (e.g., Lipinski's Rule of Five) and assessed for ADMET properties to ensure practical viability.
Q: Can the constructed libraries be directly used in experimental assays?

A: Yes. While designed primarily for virtual screening, selected compounds can be sourced from vendors or synthesized for experimental validation.
Q: How long does library construction take?

A: Typical timelines range from 2–4 weeks, depending on the size and complexity of the library.
Q: How are the libraries delivered?

A: Libraries are provided in standard formats compatible with popular virtual screening platforms, along with documentation detailing their construction process.

References:

Du Y, Yuan Y, Xu L, et al. Discovery of METTL3 small molecule inhibitors by virtual screening of natural products. Front Pharmacol. 2022;13:878135. doi:10.3389/fphar.2022.878135
Yousef RG, Ibrahim A, Khalifa MM, et al. Discovery of new nicotinamides as apoptotic VEGFR-2 inhibitors: virtual screening, synthesis, anti-proliferative, immunomodulatory, ADMET, toxicity, and molecular dynamic simulation studies. Journal of Enzyme Inhibition and Medicinal Chemistry. 2022;37(1):1389-1403. doi:10.1080/14756366.2022.2070744

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