Drug-drug interactions (DDIs) occur when the pharmacokinetic (PK) or pharmacodynamic properties of a drug are altered by the co-administration of another therapeutic agent. These interactions can lead to diminished efficacy or increased toxicity, significantly impacting the success rate of drug discovery. Therefore, early-stage DDI analysis is essential to predict potential risks involving absorption, distribution, metabolism, and excretion (ADME). BOC Sciences offers a comprehensive suite of in vitro DDI assessment services, focusing on enzyme inhibition/induction and transporter interactions. We utilize high-quality biological systems, including liver microsomes and hepatocytes, to deliver precise data that helps researchers optimize lead compounds, delineate metabolic pathways, and mitigate liability risks in the drug development pipeline.
We evaluate the potential of test compounds to inhibit or induce major Cytochrome P450 (CYP) isoforms. Our services include IC50 determination, time-dependent inhibition (TDI) assessment, and mRNA expression analysis in hepatocytes, helping you predict metabolic bottlenecks early in R&D.
Our team assesses substrate and inhibition profiles against key drug transporters (e.g., P-gp, BCRP, OATP, OCT, OAT). By utilizing polarized cell monolayers and vesicle systems, we clarify drug absorption mechanisms and potential transporter-mediated interactions affecting tissue distribution.
We identify the specific enzymes responsible for the metabolism of your drug candidate. Using recombinant enzymes and specific chemical inhibitors, we determine the fractional contribution of each pathway, enabling a clear understanding of metabolic clearance mechanisms.
BOC Sciences delivers high-throughput DDI screening and mechanistic studies to accelerate your lead optimization and candidate selection process.
BOC Sciences supports the evaluation of diverse therapeutic modalities, tailoring assay conditions to the physicochemical properties of your molecules.
Submit your compound details, and our ADME experts will design a targeted DDI testing strategy to support your lead selection and optimization.
We review your compound's properties and intended therapeutic area to recommend relevant CYP isoforms and transporters for screening.
Selection of appropriate test systems (microsomes, hepatocytes, cell lines), concentration ranges, and control inhibitors to ensure robust data.
High-precision liquid handling and LC-MS/MS bioanalysis are performed to measure parent drug depletion or metabolite formation accurately.
Calculation of kinetic parameters (IC50, Ki, Km, Vmax). We deliver a detailed scientific report with actionable insights for your R&D team.
For discovery teams needing to rank large compound libraries rapidly, we provide high-throughput CYP inhibition and metabolic stability screening. Our simplified protocols (e.g., single-point % inhibition or abbreviated IC50) offer fast turnaround times, enabling you to identify DDI liabilities and "fail fast" before investing in extensive characterization.
We support medicinal chemistry teams by establishing robust Structure-Activity Relationships (SAR) regarding metabolic interactions. By providing precise IC50 shifts (TDI) and transporter substrate data, we help chemists identify metabolic soft spots and design analogs with improved safety profiles and reduced interaction potential.
Beyond small molecules, we offer specialized DDI strategies for Antibody-Drug Conjugates (ADCs) and PROTACs. We assess the interaction potential of released cytotoxic payloads, linkers, and unique degraders, tailoring assay conditions to account for stability, solubility, and non-standard metabolic pathways involved in these novel modalities.
When routine assays flag a risk, our expert team conducts deep-dive mechanistic studies to contextualize the data. Whether determining Kinact/KI for time-dependent inhibition or distinguishing between transporter substrates and inhibitors, we provide the detailed kinetic parameters needed to build accurate prediction models.
Partner with BOC Sciences to uncover the metabolic profile of your candidates. Our reliable in vitro data empowers you to make informed decisions, minimize attrition, and accelerate your path through the drug development pipeline.
We cover the full spectrum of ADME targets, including major CYP isoforms, Phase II enzymes (UGTs), and a wide array of uptake and efflux transporters, providing a holistic view of interaction potential.
Equipped with advanced LC-MS/MS systems, we achieve superior sensitivity and selectivity, allowing for the accurate quantification of trace metabolites and parent compounds even in complex biological matrices.
Unlike rigid standard panels, we offer customizable assay conditions (incubation times, protein concentrations, probe substrates) tailored to the specific metabolic stability and properties of your molecule.
Our team consists of biochemists with deep expertise in enzyme kinetics. We don't just provide raw numbers; we offer interpretation of Ki, Kinact, and fm values to help contextually evaluate DDI risks.
Client Needs: A biotech client identified a promising heterocyclic compound but observed non-linear pharmacokinetics in preliminary rodent studies. They suspected mechanism-based inhibition (MBI) of CYP3A4.
Challenges: Standard reversible inhibition assays (IC50 shift) were inconclusive due to high non-specific binding. The client needed a definitive assessment of time-dependent inhibition to decide whether to proceed with the scaffold.
Solution: BOC Sciences implemented a rigorous two-step dilution method to effectively distinguish between reversible binding and true inactivation. We optimized protein concentrations to minimize non-specific binding and performed kinetics experiments with multiple pre-incubation time points (0–30 min). This allowed for the precise determination of KI and Kinact values, providing a quantitative measure of the inactivation rate.
Outcome: The study confirmed significant time-dependent inhibition. Based on the kinetic parameters, the client prioritized a backup series with a modified core structure, successfully eliminating the MBI liability while retaining potency.
Client Needs: A pharmaceutical company observed poor oral bioavailability for a highly soluble peptide-mimetic and suspected it was a substrate for intestinal efflux transporters.
Challenges: The compound had low permeability and high adsorption tendencies, making it difficult to distinguish between passive diffusion limitations and active efflux. Data from their internal assay was noisy and unreproducible.
Solution: We optimized the Caco-2 monolayer assay by verifying tight junction integrity with Lucifer Yellow and conducting a mass balance assessment to account for compound loss. We utilized a specific inhibitor panel (Zosuquidar for P-gp, Ko143 for BCRP) in a bidirectional transport setup. This controlled approach allowed us to calculate a definitive Efflux Ratio (ER) and confirm the specific transporter involvement without ambiguity.
Outcome: Data revealed a high Efflux Ratio (>10) that was significantly reduced by P-gp inhibitors but not BCRP inhibitors. The client used this data to guide the design of prodrugs that bypassed P-gp recognition, improving bioavailability.
Client Needs: To support the selection of a final candidate, a client needed to understand the metabolic clearance pathway of a new molecular entity (NME) to predict potential interactions with common co-medications.
Challenges: The compound was metabolized by multiple enzymes. The client needed to quantify the fractional contribution (fm) of each CYP isoform to assess if the drug was a "victim" for strong CYP inhibitors.
Solution: BOC Sciences adopted a cross-validation strategy combining two independent methods. First, we screened a panel of cDNA-expressed recombinant human CYPs (rCYPs) to identify capable enzymes. Second, we validated these findings in Human Liver Microsomes (HLM) using isoform-selective chemical inhibitors. By applying Relative Activity Factors (RAFs) scaling, we calculated the precise contribution of each pathway.
Outcome: We established that CYP2C9 was the primary clearance pathway (fm > 80%). This crucial information allowed the client to flag potential risks with CYP2C9 inhibitors early in the development strategy.
Assessing drug interaction risk requires integrating in vitro metabolism enzyme analysis, transporter screening, and computational modeling to systematically identify potential targets and metabolic pathways. BOC Sciences offers a comprehensive in vitro DDI analysis platform, covering CYP450, UGT, and major transporters, helping clients optimize candidate design and reduce development risks.
Designing in vitro metabolism studies involves selecting appropriate enzyme systems and substrate concentrations according to metabolic pathways, considering reaction time and metabolite detection. BOC Sciences provides customized experiments and data analysis for CYP, UGT, and transporter kinetics, enabling clients to fully understand drug metabolism and potential interactions.
DDI prediction combines in vitro data with computational simulations, including enzyme inhibition/induction kinetics and pharmacokinetic modeling. BOC Sciences integrates in vitro results with pharmacokinetic modeling to deliver quantitative interaction predictions and risk assessment, supporting molecule optimization and combination strategy decisions.
Identifying high-risk drugs requires examining enzyme dependency, transporter substrate properties, and systemic exposure levels. BOC Sciences offers comprehensive drug-enzyme/transporter interaction screening, using in vitro experiments and kinetic analysis to accurately detect potential high-risk combinations, providing clients with scientific guidance for development strategy.
Drug combination optimization relies on interaction risk assessment and metabolic profile analysis, selecting low cross-metabolism pathways or adjusting doses to achieve safe and effective combinations. BOC Sciences provides systematic in vitro interaction analysis and simulation support to design optimal drug combinations and reduce potential adverse interactions.
The reaction phenotyping data provided by BOC Sciences was exceptional. Their determination of fm values was precise, and the report provided the mechanistic clarity we needed to understand our compound's clearance. A highly professional team.
— Dr. Anderson, Principal Scientist, DMPK
We used BOC Sciences for CYP inhibition screening of our library. The turnaround time was fast, and the data quality allowed us to rank our compounds confidently. Their support in interpreting borderline results was very helpful.
— Dr. Mitchell, Director of Medicinal Chemistry
When we faced complex transporter issues, BOC Sciences designed a custom assay protocol that differentiated between uptake and efflux mechanisms. Their scientific insight saved us weeks of trial and error in the lab.
— Dr. Thompson, Senior Researcher, Biotech Startup
The final reports are thorough and well-organized. Having all the experimental conditions, controls, and raw data clearly presented made it easy for us to integrate the results into our internal project reviews.
— Dr. Roberts, VP of Preclinical Development
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