Enzyme Inhibitor Screening Service

Enzyme Inhibitor Screening is a core service in drug discovery and mechanistic biochemistry, aimed at identifying small molecules or compounds that decrease or block the activity of a target enzyme. This high-throughput process involves testing large chemical libraries against the enzyme to find "hit" compounds that show preliminary inhibitory activity. The goal is to rapidly identify novel scaffolds that can be optimized into potent therapeutic leads or specific biochemical probes.

CD Biosynsis offers robust and flexible CRO services for Enzyme Inhibitor Screening. Our platform utilizes validated, sensitive enzymatic assays optimized for stability and miniaturization, enabling the rapid testing of diverse compound collections, including commercial libraries, natural product extracts, and focused chemical sets. We employ automated liquid handling and multi-mode detection systems to accurately measure inhibition across different concentrations, delivering quantitative IC50 values and facilitating the immediate selection of promising candidates for subsequent lead optimization and mechanistic studies.

Highlights

Our inhibitor screening platform ensures efficiency, reliability, and depth in identifying high-quality lead candidates.

• High-Throughput and Miniaturization: Screening of hundreds of thousands of compounds in 384- or 1536-well plates for rapid hit identification.
• Quantitative IC50 Determination: Accurately measure the half maximal inhibitory concentration for all confirmed hit compounds.
• Assay Robustness and Validation: Utilize Z'-factor and signal-to-noise ratios to ensure high confidence and minimal false positives/negatives.
• Mechanism of Action (MOA) Triage: Initial screening to identify reversible vs. irreversible inhibitors and potential non-specific (pan-assay interference) compounds.

Applications

Inhibitor screening is the foundation of small molecule drug discovery and biological pathway analysis:

Lead Compound Discovery

           

Identification of novel chemical scaffolds that inhibit disease-associated enzyme targets (e.g., kinases, proteases) for therapeutic development.

Target Validation and Pathway Mapping

Use of specific inhibitors as biochemical tools to validate the function of a target enzyme within a cellular signaling or metabolic pathway.

Mechanism-Based Drug Design

Selecting inhibitors with unique or desirable binding kinetics (e.g., allosteric, covalent) for optimization.

Repurposing and Off-Target Screening

Screening existing FDA-approved drug libraries against new targets or screening lead compounds against off-targets to predict toxicity.

Platform

Our Inhibitor Screening platform integrates best-in-class automation, assay chemistries, and quality control metrics.

Compound Libraries Access

Access to diverse chemical libraries (tens to hundreds of thousands of compounds) and focused sets (e.g., kinase, protease inhibitors).

Automated Robotics and HTS

Fully integrated robotic systems for high-speed liquid handling, precise reagent dispensing, and minimized variability.

Diverse Assay Technologies

Expertise in FRET, TR-FRET, AlphaScreen, radiometric assays, and absorbance/fluorescence-based techniques adaptable to nearly any enzyme class.

Purity and Integrity Checks

Pre-screening QC of compound libraries for solubility and structural integrity to minimize artifacts.

Statistical Hit Confirmation

Robust statistical analysis (e.g., Z'-factor, Curve Fitting) for reliable hit selection and ranking.

Workflow

Our Inhibitor Screening workflow moves systematically from assay development and validation to hit confirmation and initial characterization:

• Assay Optimization and Validation: Optimize enzyme, substrate, and buffer concentrations; establish robust HTS parameters and calculate Z'-factor.
• Primary Screening (Single Concentration): Test the entire compound library at a fixed concentration against the target enzyme to identify initial hits (>50% inhibition).
• Hit Confirmation and Dose-Response: Re-test all primary hits and perform a 8-12 point concentration series to generate reproducible inhibition curves.
• IC50 Determination and Triage: Calculate IC50 values through non-linear regression and triage hits based on potency, structure, and early MOA indications.
• Reporting: Deliver a comprehensive report including a ranked list of hits, IC50 values, curve fit quality, and recommendations for secondary kinetics (Ki) and lead optimization.

CD Biosynsis delivers high-confidence, actionable data for rapid progression into lead optimization phases. Every project includes:

• Primary Screening Data: Inhibition percentage for all compounds tested.
• Ranked Hit List: Confirmed hits prioritized by potency and IC50 values.
• Dose-Response Curves: High-quality graphical representation of inhibition for confirmed hits.
• Z'-Factor and Quality Metrics: Full validation statistics ensuring assay robustness.