Drug Screening and Evaluation Services
Rare liver diseases require precise therapeutic strategies due to their genetic heterogeneity and limited treatment options. Protheragen's integrated drug discovery platform combines high-content phenotypic screening, mechanistic validation, and translational models to accelerate candidate identification and optimization across therapeutic modalities—from small molecules to advanced cell/gene therapies. Our services streamline preclinical development, validated in disease-specific models, to advance targeted treatments for rare liver disease patients.
Overview
Challenges in Conventional Approaches
Rare liver diseases exhibit complex genetic and molecular mechanisms (e.g., SERPINA1 dysfunction in AATD, ATP7B defects in Wilson disease) that conventional cell/animal models often fail to replicate. This mismatch contributes to high attrition rates in drug development and complicates regulatory approval due to insufficient preclinical relevance.
Technological Breakthroughs
Modern platforms address these limitations:
- CRISPR-based target discovery: Identifies disease-specific targets like ABCB11 in PFIC.
- Liver-on-a-chip systems: Models human-specific cholestasis and fibrosis dynamics.
- AI-enhanced ADMET prediction: Integrates AlphaFold structural insights for early hepatotoxicity screening.
Integrated Screening Solutions
Our services leverage these advancements to deliver:
- Modality-specific workflows: RNAi screening for gene silencing, small molecule optimization for metabolic disorders.
- Human-relevant validation: Combine multi-omics data with functional assays in disease-mimetic models.
- Regulatory-ready datasets: Robust preclinical evidence packages to accelerate IND submissions.
Fig1. The diagram of liver organoid-based Toxicity screen (LoT). (Shinozawa, et al., 2021)Our Services
To address the complex needs of rare liver disease drug development, we offer a complete suite of screening and evaluation services:
Targeted Drug Screening
We perform mechanism-based drug discovery by validating disease-specific targets and employing high-throughput screening (HTS) platforms to systematically evaluate compound activity, selectivity, and therapeutic potential. Our workflows integrate target optimization with functional assays to prioritize candidates aligned with disease pathology.
High-Throughput Screening
Our automated HTS platforms enable rapid evaluation of large compound libraries (>100,000 molecules), combining robotic liquid handling and assay miniaturization with multiparametric readouts. Hit validation is enhanced by multi-omics data integration, followed by lead optimization to refine potency and specificity.
Cell Therapy Development
We support hepatic cell therapy development through hepatocyte transplantation protocols, CAR-T/MSC therapy optimization, and preclinical safety/efficacy assessments. Services include cell line characterization, engraftment monitoring in disease-relevant models, and immunogenicity profiling to meet regulatory requirements.
Gene Therapy Development
Our gene therapy pipelines utilize CRISPR/Cas9 for precise correction of disease-associated mutations (e.g., SERPINA1, ATP7B) and optimize viral vectors (AAV, lentivirus) for liver-specific delivery. Preclinical studies assess biodistribution, durability of gene expression, and off-target effects to ensure therapeutic safety.
RNA Therapeutics
We develop RNA-based therapies through siRNA/shRNA design for targeted gene silencing and optimize lipid nanoparticle (LNP) formulations for mRNA delivery. Services include RNA stability testing, pharmacokinetic profiling, and immunogenicity evaluation to balance efficacy and safety.
Natural Product Screening
We systematically screen curated natural product libraries (>50,000 plant/microbial extracts) using disease-specific assays for fibrosis, cholestasis, and metabolic dysfunction. Active compounds undergo ADMET prediction, mechanistic studies, and lead optimization to identify clinically translatable candidates.
Why Choose Us?
- Integrated Technology Platform
We provide end-to-end services spanning drug screening, lead optimization, and toxicological evaluation, supporting all phases of therapeutic development for rare liver diseases.
- Customized Solutions
Project-specific workflows are designed to address unique research objectives, from initial compound screening to preclinical validation, with protocol adjustments based on therapeutic modality (small molecules, biologics, cell/gene therapies).
- Expert Scientific Team
Our multidisciplinary team offers technical consultation and experimental design support, leveraging expertise in hepatology, pharmacokinetics, and regulatory requirements to optimize study outcomes.
- Data Quality Assurance
Standardized operating procedures and advanced analytical platforms (LC-MS/MS, NGS, high-content imaging) ensure reproducible, audit-ready datasets compliant with FDA/EMA preclinical guidelines.
FAQs?
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Q: Which therapeutic modalities do you support?
A: Our services cover small molecule discovery, biologic therapeutics (e.g., monoclonal antibodies), gene therapies (CRISPR/Cas9, AAV vectors), and RNA-based modalities (siRNA, mRNA) targeting rare liver disease pathways.
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Q: What is your screening throughput capacity?
A: Primary screening workflows process up to 100,000 compounds weekly using automated liquid handling systems, followed by secondary validation for hit confirmation and prioritization.
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Q: What is the typical project timeline?
A: Standard high-throughput screening projects require 1-3 months, depending on scope (e.g., single-target vs. multi-omics analysis) and validation depth (IC50 determination, selectivity profiling).
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Q: Do you conduct drug metabolism studies?
A: Yes. We perform ADME (absorption, distribution, metabolism, excretion) assessments using hepatocyte models and LC-MS/MS analysis to optimize pharmacokinetic properties and dosing regimens.
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Q: Which technologies are central to your workflows?
A: Our pipelines integrate robotic screening platforms, high-content imaging, mass spectrometry (LC-MS/MS), and CRISPR-engineered disease models. All workflows adhere to standardized quality control protocols for reproducible, high-confidence data generation.
Reference
- Shinozawa T.; et al. High-Fidelity Drug-Induced Liver Injury Screen Using Human Pluripotent Stem Cell-Derived Organoids. Gastroenterology. 2021;160(3):831-846.e10.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.