Enterprise AI Analysis
In silico analysis of isoquinoline alkaloids using Cathepsin L as target receptor for controlling metastasis
Metastasis, a critical challenge in cancer treatment, is often driven by proteolytic enzymes like Cathepsin L. With existing inhibitors limited, our enterprise embarked on a comprehensive in-silico screening to identify novel antimetastatic agents from natural isoquinoline alkaloids. This initiative leverages advanced computational methodologies to accelerate drug discovery and optimize therapeutic development.
Our analysis, employing molecular docking and dynamic simulations, revealed Isoliensinine and Dauricine as exceptionally promising Cathepsin L inhibitors. These compounds exhibited significantly superior binding affinities compared to the current clinical standard, Olegatrelvir. Further ADMET profiling confirmed their favorable drug-likeness and safety, paving the way for a new generation of targeted cancer therapies.
Executive Impact & Key Metrics
This research underscores the power of AI in identifying potent therapeutic candidates with improved efficacy and favorable safety profiles, leading to significant advancements in antimetastatic drug development.
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Lead Compound Efficacy Boost
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Average RMSD for Dauricine-2XU4 Complex
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Favorable Bioavailability Score
Deep Analysis & Enterprise Applications
Select a topic to dive deeper, then explore the specific findings from the research, rebuilt as interactive, enterprise-focused modules.
Molecular Docking Efficacy
Structural Stability & Dynamics
ADMET Profile Validation
Binding Mechanism Elucidation
Superior Binding Affinities Identified
Our molecular docking analysis rigorously compared ten isoquinoline alkaloids against Cathepsin L (PDB ID: 2XU4). This module presents the top-performing compounds, detailing their binding energies and crucial non-covalent interactions, highlighting their enhanced inhibitory potential over existing treatments.
| Compound | Binding Energy (kcal/mol) | Key Interactions |
|---|---|---|
| Isoliensinine | -9.6 |
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| Dauricine | -9.1 |
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| Sanguinarine | -9.1 |
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| Olegatrelvir (Standard) | -9.0 |
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| DJT (Cocrystallized Ligand) | -6.5 |
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Robust Protein-Ligand Complex Stability
Molecular Dynamics simulations for 200 ns revealed the dynamic behavior of Isoliensinine and Dauricine when bound to Cathepsin L. This module showcases the exceptional stability of these complexes, as quantified by their Root Mean Square Deviation (RMSD) values, indicating sustained inhibitory potential.
1.36 Å
Average RMSD of Dauricine-2XU4 Complex
Our simulations demonstrated that Isoliensinine and Dauricine consistently maintain optimal binding conformations, with Dauricine exhibiting an average RMSD of 1.36 Å, signifying a highly rigid and stable complex over the 200 ns simulation period. This stability is crucial for sustained therapeutic efficacy.
Ensuring Clinical Viability Through ADMET Profiling
Before advancing to costly in-vitro and in-vivo stages, robust ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity) predictions are essential. This flowchart illustrates our rigorous screening process, confirming the favorable pharmacokinetic and safety profiles of our lead isoquinoline alkaloids, Isoliensinine and Dauricine.
Enterprise Process Flow
High GI Absorption Confirmed
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Non-CYP2C19 Inhibitory Action
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Weak hERG Inhibition (Low Cardiac Risk)
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Non-Carcinogenic & Non-AMES Toxic
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Acute Oral Toxicity Category-3 (Nontoxic)
Unveiling the Molecular Basis of Inhibition
A deep dive into the molecular interactions provides crucial insights into how Isoliensinine and Dauricine effectively inhibit Cathepsin L. This case study highlights the specific hydrogen bonds, hydrophobic contacts, and pi-stacking interactions that contribute to their high binding affinity and conformational stability, guiding future lead optimization strategies.
Precision Binding: How Isoliensinine and Dauricine Block Cathepsin L
Isoliensinine forms a robust complex with Cathepsin L (2XU4) through 3 hydrogen bonds with Glutamine 18, 19, and Asparagine 66, alongside 3 hydrophobic interactions (Trp 189, Leu 144, Gln 21) and 1 pi-stacking interaction. The presence of its alkoxy groups significantly enhances these stable interactions. Dauricine, while having fewer direct hydrogen bonds (1 with Leu 144), benefits from 2 key hydrophobic interactions (Trp 189, Gly 20) and the conformational stability provided by its furan ring. Both compounds exhibit strong non-covalent interactions crucial for their potent inhibitory activity.
Quantify the Impact: AI-Driven Drug Discovery ROI
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Potential Annual Savings
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Your Path to Accelerated Drug Discovery
Our phased approach ensures seamless integration of AI-powered screening into your existing R&D pipeline, delivering tangible results at every step.
Discovery & Pre-Clinical Validation
Initial in-silico screening, molecular docking, MD simulations, and ADMET predictions to identify robust lead compounds with optimal binding affinities and favorable safety profiles.
Lead Optimization & Experimental Validation
Chemical synthesis of top candidates, followed by in-vitro and in-vivo assays to experimentally confirm inhibitory activity against Cathepsin L and antimetastatic effects in relevant cancer models.
Clinical Development Strategy
Development of comprehensive formulation, toxicology, and regulatory strategies based on the validated lead compounds, preparing for future clinical trials and human studies.
Commercialization & Market Entry
Strategic partnerships, intellectual property protection, and market access planning to bring novel antimetastatic therapies to patients, maximizing societal and economic impact.
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