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In Vitro ADME Assays and Services

Welcome to ICE Bioscience, where our cutting-edge ADME (Absorption, Distribution, Metabolism, and Excretion) services pave the way for optimized drug discovery and development. With a deep understanding of the critical role ADME properties play in pharmaceutical success, we offer comprehensive in vitro ADME studies tailored to meet the unique demands of diverse drug development projects.

Our in vitro ADME service portfolio spans a wide range of small molecule drugs, and we have accumulated extensive experience and strategies in this domain. From bioavailability assessments in the Lead Finding stage to intricate metabolic stability and transporters related to drug interaction studies in the Lead Optimization and Pre-Clinical Candidate stages, we offer a comprehensive suite of services.

We recognize the importance of early ADME assessment in mitigating risks and expediting the drug development process. Our services are designed to support your project at every stage, increasing the probability of successful drug candidates.


Features of Our DMPK Services

✅ Comprehensive Molecular Type Detection: Detection of various biomarkers such as small molecules, peptides, PDCs, ADCs, small nucleic acids, neurotransmitters, nucleotides, and other endogenous substances.

✅ Customized Services: Flexible experiment design with customized plans based on specific requirements.

✅ Systematic data interpretation: Metabolite Identification with professional interpretation and strong information confidentiality.

✅ SLC Transporter Platform: Compliance with FDA-recommended SLC and special transporter requirements.

Collaborative exploration of new targets based on mass spectrometry platform: Integrated services with diverse options (FTE or FFS).

Support for regulatory filings.


Our Tier 1 and Tier 2 ADME Panels offer in vitro assays for quick and comprehensive analysis. The Tier 1 Panel swiftly profiles essential properties for selecting candidates with favorable pharmacokinetic profiles. The Tier 2 Panel provides detailed ADME data to enhance the characterization of metabolism and excretion pathways for lead candidates.


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Tier 1 ADME panel

▪ Solubility

            LC-MS/MS, PBS, SGF, SIF

▪ Permeability: Caco-2, pH 6.5/7.4

▪ Protein binding: Plasma, human

▪ Intrinsic clearance

            Liver microsomes, human

▪ Lipophilicity

            Log D or Log P

Tier 2 ADME panel

▪ CYP Inhibition

▪ CYP time-dependent inhibition

▪ CYP Phenotyping

▪ CYP Induction (upcoming)

            human hepatocytes

▪ P-gp substrate assessment (Caco-2)

▪ BCRP substrate assessment (Caco-2)

▪ Transporter Inhibition


Below is a list of our in vitro ADME screening services.


Solubility

- Kinetic solubility: The maximum concentration of a compound that dissolves in a solvent under a specific timeframe, providing insights into its dissolution behavior.

- Thermodynamic solubility: The equilibrium concentration of a compound in a solution, offering information about its long-term solubility characteristics.

Lipophilicity

- LogP (Partition Coefficient): A logarithmic ratio of the concentration of a compound in octanol to its concentration in water at equilibrium.

- LogD Extending the concept of LogP by considering the ionization of acidic or basic functional groups.

Stability

- Chemical stability in buffer: Ensuring the maintenance of a drug's potency, safety, and efficacy over time. Factors such as pH, temperature, and the presence of reactive impurities can influence the chemical stability of a compound in a buffer.

- Liver microsomes, S9, hepatocytes Stability: Assessing the compound's resilience in the presence of hepatic enzymes, mimicking conditions encountered in the liver during drug metabolism.

- Biological Matrix Stability (Plasma, Blood, Tissue Homogenates): Evaluating the robustness of a compound in biological fluids or tissue homogenates, reflecting its stability in physiological environments.

- Glutathione (GSH) Stability: Focusing on the compound's integrity in the presence of glutathione, a key cellular antioxidant, providing insights into potential interactions and susceptibility to degradation.

Permeability

- Parallel Artificial Membrane Permeability Assay (PAMPA):  Measuring a compound's permeability across an artificial lipid membrane, serving as a predictive tool for oral absorption.

- Caco-2: Evaluating a compound's ability to traverse human intestinal epithelial cells, helping predict its absorption potential in the gastrointestinal tract.

- MDCK-MDR1, MDCK-BCRP: Cells expressing the P-glycoprotein (MDR1) and the breast cancer resistance protein (BCRP), assessing the impact of efflux transporters on a compound's permeability.

Transporter

- ABC Transporter Assay: Employing both cell and vesicle assays, our comprehensive ABC transporter evaluation includes essential transporters such as P-glycoprotein (P-gp), Breast Cancer Resistance Protein (BCRP), Multidrug Resistance-Associated Proteins (MRPs) 1-4, and Bile Salt Export Pump (BSEP).

- SLC Transporter Assay: Leveraging stable transfected HEK293 cells, our SLC transporter assessment covers key transporters including OATP1B1, OATP1B3, OAT1, OAT3, OCT1, OCT2, MATE1, and MATE2K.

CYP Phenotyping

- CYP phenotyping Identifying the specific cytochrome P450 (CYP) isoforms involved in the metabolism of a compound, aiding in understanding its biotransformation pathways.

- CYP isoforms: 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 3A4, specific isoforms of cytochrome P450 enzymes responsible for drug metabolism in the liver, and their identification helps predict potential drug interactions.

Drug Drug Interaction

- DDI (Drug-Drug Interaction): DDI studies assess how a drug may affect the pharmacokinetics of another drug, providing valuable information to avoid adverse interactions in co-administration scenarios.

- TDI (Time-Dependent Inhibition): TDI studies focus on the potential of a drug to inhibit enzymes in a time-dependent manner, affecting its own metabolism and potentially leading to drug-drug interactions.

Protein Binding

- Plasma binding: Investigating the extent to which a drug binds to proteins in the blood plasma, influencing its distribution and pharmacokinetic profile.

- Tissue homogenates: Evaluating the binding of a drug to proteins in tissue homogenates, providing information on its distribution within tissues.

- BSA or target protein: Assessing the interaction between a drug and specific proteins, impacting its distribution and efficacy.

Blood Plasma Ratio

- Blood Plasma Ratio: A measure of the distribution of a substance between the blood plasma and the whole blood. This ratio provides valuable information about the extent to which a compound binds to blood cells versus remaining in the liquid plasma component. Aid in understanding the pharmacokinetics and pharmacodynamics of the compound and predicting potential hematotoxicity or other adverse effects.

Metabolite Profiling and Identification

- MetID In Vitro: Using liver microsomes and hepatocytes to identify and characterize metabolites produced during drug metabolism.

- MetID In Vivo: Analyzing metabolites in biological fluids such as plasma, urine, feces, and bile, providing a comprehensive understanding of drug metabolism in living organisms.

Cytotoxicity

- HepG2: Cytotoxicity studies using HepG2 cells assess the potential toxic effects of a compound on liver cells, impacting its safety profile.

- Primary Human Hepatocytes: Cytotoxicity studies with primary human hepatocytes evaluate the impact of a compound on the viability of human liver cells, crucial for assessing safety in drug development.


Contact Us

We value your inquiries and are here to provide you with tailored solutions for your drug discovery and development needs. Whether you have questions, require more information, or are interested in discussing potential collaborations, our team of experts is just a message away.
Feel free to reach out to us.

We are a CRO service organization, not a hospital