PROTAC Bioavailability Prediction Service
PROTAC bioavailability assessment is a key component in the study of the efficacy and in vivo behavior of these bifunctional molecules. CD ComputaBio's prediction service is designed to analyze the properties of PROTAC molecules in terms of absorption, distribution, metabolism, excretion, and toxicity (ADMET) by using computational biology and chemoinformatics techniques.
Introduction to PROTAC Bioavailability
PROTAC molecules, which typically have large molecular weights (ranging from ~700 to 1000 Da) and complex structures (featuring linkers and dual-targeting ligands), face unique bioavailability challenges, including poor membrane permeability, rapid metabolism, and suboptimal tissue distribution, limiting oral absorption and tissue distribution. Optimizing logP, solubility, and stability via chemical modifications (e.g., prodrugs) or delivery systems (e.g., nanoparticles) enhances systemic exposure. Improved bioavailability maximizes target engagement while reducing dosing frequency and off-tissue toxicity.
Fig. 1 Mechanism of PROTAC. (Rej R K, et al., 2024)
Our Services
Addressing the unique challenges of PROTAC's high molecular weight and ternary complex stability, CD ComputaBio utilizes state-of-the-art artificial intelligence modeling, multi-scale molecular dynamics, and physiological pharmacokinetic (PBPK) simulations to predict and optimize PROTAC bioavailability - all without the need for expensive wet-lab experiments.
Plasma Protein Binding Affinity Prediction
Molecular docking models against serum proteins (HSA/AGP) quantify PROTAC-plasma protein interactions. Free energy change calculations estimate free drug concentrations to evaluate effective in vivo distribution levels.
Transmembrane Permeability Prediction
Machine learning-driven QSAR models combined with logP and polar surface area calculations predict PROTAC penetration efficiency across intestinal/blood-brain barriers. Virtual membrane permeability experiments screen candidates with optimal cellular membrane penetration potential.
Metabolic Stability Computational Prediction
CYP450 metabolism site prediction integrated with ADMET profiling constructs PROTAC metabolic trees. Half-life simulations and metabolite toxicity screening identify liver enzyme-vulnerable fragments, guiding anti-metabolic structural modifications.
PK/PD Modeling and Simulation
Our PK/PD models and simulation platform predicts tissue-specific degradation efficiency-time curves, quantifies E3 ligase recycling thresholds for sustained efficacy, and optimizes dosing regimens by correlating PROTAC linker chemistry with plasma half-life extension.
The Process of PROTAC Bioavailability Prediction Service
Modeling and Simulation - Using advanced software tools and algorithms, we perform molecular modeling and simulation studies to predict the behavior of PROTAC molecules in biological systems, allowing us to assess their pharmacokinetic and pharmacodynamic properties.
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Reaction Pathway Study - Our simulations help map potential energy surfaces and identify optimum reaction pathways, leading to insights for enzyme catalysis and reaction mechanisms.
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Data Analysis and Interpretation - Beyond conducting simulations, we offer comprehensive data analysis services to extract meaningful conclusions from simulation results. We employ statistical methods and visualization techniques to elucidate the underlying mechanisms governing molecular interactions
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Our Core Technologies
PROTAC-Specific QSAR Architectures
GNN-based models trained on 1,200+ PROTACs predict membrane penetration (R²=0.88).
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Metabolic Vulnerability Hotspot Mapping
ML-powered fragment analysis identifies PROTAC cleavage sites 3x faster than traditional methods.
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Multiscale PK/PD Orchestrator
Links ternary complex stability to systemic degradation via hybrid modeling (validated on 17 clinical PROTACs).
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Plasma Protein Binding Atlas
HSA/AGP affinity database with FEP-calibrated predictions (800+ warheads, Pearson's r=0.91).
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Advantages of Our Services
Cost-effective
By using computational modeling, we can reduce the time and cost associated with traditional experimental approaches to bioavailability assessment.
Accuracy
Our advanced algorithms and models provide accurate predictions for PROTAC molecules, leading to improved drug development outcomes.
Customized solutions
We work closely with our clients to tailor our services to their specific needs, ensuring the success of their drug development projects.
CD ComputaBio stands as a leader in bioavailability assessment and toxicity prediction of PROTAC molecules through advanced computational modelling. Our commitment to excellence, coupled with our expertise in leveraging cutting-edge technologies, enables us to provide tailored services that meet the unique needs of our clients in the pharmaceutical industry. For detailed inquiries or collaboration opportunities, please feel free to contact us.
Reference:
- Rej R K.; et al. Orally Bioavailable Proteolysis-Targeting Chimeras: An Innovative Approach in the Golden Era of Discovering Small-Molecule Cancer Drugs[J]. Pharmaceuticals. 2024, 17(4): 494.
* For Research Use Only.
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