In Vitro ADME & Physicochemical Profiling

In vitro ADME studies provide critical insights into a compound’s absorption, distribution, metabolism and excretion (ADME) properties. Data obtained from Sygnature Discovery’s robust ADME services are utilized to predict a drug candidates potential for success by assessing its bioavailability, stability and metabolic fate in vivo. By identifying potential liabilities early, our assays support informed decision-making, improving the likelihood of clinical success.

Comprehensive ADME & Physicochemical Profiling

Sygnature Discovery offers a broad range of in vitro pharmacokinetic assays designed to predict clinical drug concentrations in the body and tissues. Our ADME and physicochemical profiling services allow researchers to:

• Profile compounds efficiently for optimal ADME properties
• Optimize drug candidates for better absorption and bioavailability

Our services support preclinical drug screening for lipophilicity, solubility, stability and permeability – key factors in successful drug development.

Lipophilicity Profiling

Lipophilicity, or a molecule’s affinity for lipid environments, is a fundamental property influencing ligand efficiency, membrane permeability, and pharmacokinetics. It play a crucial role in determining a drug’s ability to cross lipid membranes, its GI absorption, and its interaction with biological targets.

Balancing lipophilicity is critical: excessive lipophilicity can lead to low solubility, high metabolism, tissue accumulation and potential toxicity, while excessive hydrophilicity can reduce permeability and target binding.

Lipophilicity Services

• LogD
• ChromLogD
• EPSA

Solubility Screening

Solubility is a key determinant of a drug’s success. Poor solubility can be detrimental to the performance of in vitro assays, and in vivo affects GI absorption and bioavailability, ultimately influencing therapeutic exposure. Sygnature Discovery provides comprehensive solubility profiling to support drug delivery strategies.

Solubility Screening Services

Our solubility screening services assess a compound’s behaviour in different aqueous environments, enabling optimized drug absorption. We offer:

• Kinetic Solubility Assay – Screening to estimate solubility at an early stage to aid study design and assist in the interpretation of in vitro data.
• Thermodynamic Solubility Assay – The gold standard for solubility assessment, evaluating solid-form dissolution across buffer systems.

Our Form & Formulation team also provides tailored solubility enhancement strategies using approaches such as solubilizers, nanoparticles and salt forms.

Permeability Assessment

For an orally administered drug to be effective, it must be absorbed by the gastrointestinal tract. Permeability is a crucial determinant of drug absorption and blood-brain barrier (BBB) penetration.

Permeability Services

Sygnature Discovery’s in vitro permeability assays include:

• Caco-2 Permeability Assay – Predicts intestinal absorption using human colorectal epithelial cells.
• MDCK Assay – Evaluates BBB permeability using MDR1-transfected kidney cells. BCRP transfected MDCK cells are are also available for assessment and is responsible for the distribution and elimination of substrates to many organs such as the brain and GI tract.
• PAMPA Assay – High-throughput screening for passive permeability across lipid membranes.

By assessing apparent permeability and efflux liability, our services support drug absorption predictions in preclinical studies.

Binding Studies

The fraction unbound (Fu) of a drug determines its pharmacologically active concentration. Sygnature Discovery offers binding assays to support PK and pharmacology data interpretation.

Binding Services

• Plasma Protein Binding Assay – Determines the Fu using Rapid Equilibrium Dialysis (RED), supporting in vivo pharmacokinetic data interpretation and understandings.
• Tissue Binding Assay – Evaluates drug binding in brain homogenates to assess CNS penetration. Additional assays are available for blood, organs and tumours to better understand distribution in vitro.
• Blood-Plasma Partitioning – Measuring drug distribution between whole blood and plasma, helping to predict in vivo behaviour and ensure accurate pharmacokinetic modelling.

Stability Testing

Stability is a key factor in drug development determining unbound compound exposure levels and thus affecting both therapeutic efficacy and safety.

Stability Services

Sygnature Discovery provides metabolic stability assessments to evaluate:

• Microsomal Stability Assay – Predicts in vivo metabolism using liver microsomes.
• Hepatocyte Stability Assay – Evaluates clearance rates using primary human hepatocytes.
• Plasma Stability Assay – Assesses potential compound degradation in plasma.
• Blood Stability Assay – Ensures stability in whole blood, preventing misinterpretation of pharmacokinetic results.
• Chemical Stability Assay – Tests compounds integrity in buffer solution to prevent assay interference and to assess potential for pH dependent chemical degradation in vivo.

Drug-Drug Interaction (DDI) Studies

With polypharmacy on the rise, DDI risk assessment is critical. Sygnature Discovery offers comprehensive CYP inhibition and induction assays to evaluate drug-drug interactions.

DDI Services

• CYP Inhibition
  • Reversible CYP Inhibition Assay – Evaluates potential enzyme inhibition using isoform specific substrates.
  • Time-Dependent Inhibition (TDI) Assay – Identifies inhibition caused by metabolite formation or enzyme inactivation.
  • K_inact/K_i Parameter Assessment – Measures inhibition kinetics for clinical relevance.
• CYP Reaction Phenotyping Assay – Identifies metabolic pathways of a compound, supporting prediction of drug-drug interactions and inter-individual variability.
• CYP Induction Assay – Assesses CYP enzyme induction via mRNA expression analysis using RT-qPCR, providing a sensitive measure of transcriptional activation.

Partner with Sygnature Discovery

Sygnature Discovery provides integrated DMPK services designed to optimize drug properties and support confident decision-making at every stage of discovery. Combining high-throughput ADME screening with advanced technologies, our team of ADME and physiochemical experts delivers reliable, data-rich insights to guide compound selection and accelerate project progression.