Metabolic Stability & CYP Prediction

Home ServicesADMET & Drug-Likeness PredictionMetabolic Stability & CYP Prediction

Overview

Metabolism decides how long a compound survives and whether it can be dosed alongside other drugs. We predict microsomal and hepatocyte stability, identify the sites of metabolism that drive clearance, assess inhibition across the major cytochrome P450 isoforms, and flag structures likely to generate reactive metabolites. The practically useful part is the soft-spot map: it tells the chemistry team exactly which position to block, fluorinate or replace.

Schematic: properties are predicted across the series and each liability is attributed to the substructure responsible, so the result points to a modification.

Key Advantages

Soft Spots Mapped To Atoms

Sites of metabolism are predicted at atom level and ranked by likelihood, converting a stability problem into a specific, actionable structural modification.

Isoform-Resolved CYP Assessment

Inhibition is predicted per isoform across 1A2, 2C9, 2C19, 2D6 and 3A4, since drug–drug interaction risk depends on which enzyme is involved and on the co-medication landscape.

Reactive Metabolite Alerts

Structural alerts and predicted bioactivation pathways are reported with the mechanism, which matters for idiosyncratic toxicity risk and for regulatory discussion.

Metabolite Structures Proposed

Likely metabolite structures are generated, helping analytical teams design the identification study rather than search blind.

Where This Service Is Used

Diagnosing rapid clearance observed in microsomal or hepatocyte assays

Guiding structural blocking of a metabolic soft spot in a lead series

Assessing drug–drug interaction risk ahead of candidate selection

Screening for reactive metabolite liabilities in a series carrying structural alerts

Supporting metabolite identification studies by predicting what to look for

Methods and Techniques Applied

Site-of-metabolism prediction for major P450 isoforms with atom-level ranking

Intrinsic clearance and half-life prediction for microsomal and hepatocyte systems

CYP inhibition prediction per isoform, with reversible and time-dependent inhibition distinguished where models permit

Metabolite structure generation for the most probable transformation pathways

Structural alert screening for bioactivation and reactive intermediate formation

Series-level interpretation relating predicted stability to the structural changes across the SAR

What We Need From You

Compounds as SMILES or SDF with stereochemistry defined

Any measured stability, clearance or CYP inhibition data available for calibration

Species of interest, since human, rat, mouse and dog metabolism differ substantially

Known metabolites or metabolite identification data if a study has already been run

What You Receive

Predicted stability and clearance values per compound with confidence indicators

Soft-spot maps highlighting predicted sites of metabolism on each structure

CYP inhibition profile by isoform with interaction risk commentary

Proposed metabolite structures for the dominant predicted pathways

Structural modification recommendations targeted at the specific liabilities identified

What We Compute and Report

Predicted intrinsic clearance and half-life for microsomal and hepatocyte systems, by species

Atom-level site-of-metabolism ranking showing exactly which positions are vulnerable

Inhibition likelihood for each major cytochrome P450 isoform

Proposed metabolite structures for the dominant predicted transformation pathways

Bioactivation and reactive metabolite alerts with the mechanism identified

Interpretation and Limitations

Computational predictions prioritise hypotheses; they do not independently establish binding, biological activity, therapeutic efficacy, safety or clinical validity. Performance depends on input quality, target class, the structural evidence available and the applicability domain of the selected methods. Scores used for ranking are comparative devices and should not be read as measured quantities. All deliverables are for research use only and are not intended for diagnostic or therapeutic use.

Specifications

Item	Specification	Notes
Compounds per run	1–20,000	Soft-spot mapping is delivered per compound
Typical turnaround	5–10 working days	Including metabolite proposals and interpretation
CYP isoforms	1A2, 2C9, 2C19, 2D6, 3A4	Additional isoforms on request where models exist
Species	Human, rat, mouse, dog	Species-specific models applied where available

Service Workflow

Step 01

Scientific Consultation

We discuss the objective, the decision it supports and the data you hold. Nothing is quoted before we understand what the result has to answer.

Step 02

Feasibility Review

We check that the data, target class and available structural evidence can support the proposed approach, and say plainly where they cannot.

Step 03

Technical Proposal

Scope, methods, deliverables, timeline and price are confirmed in writing, together with the limitations we expect to report.

Step 04

Computation and QC

The analysis runs on pinned tool versions in a containerised environment, with quality checkpoints and method comparison where that is informative.

Step 05

Report and Follow-Up

You receive the ranked results, the documented methods, the limitations and a proposed validation plan, plus support in interpreting them.

Is This the Right Service for You?

Choose this service when

Microsomal or hepatocyte clearance is too high and the cause is unclear

Drug–drug interaction risk needs assessing ahead of candidate selection

An analytical team needs structural hypotheses for unidentified metabolite peaks

Consider another service when

Exposure is limited by absorption rather than by metabolism

Absorption & Permeability Prediction

The concern is reactive metabolite toxicity rather than clearance

Toxicity & Safety Profiling

What Goes Wrong, and How We Handle It

The failure modes that produce confident-looking results which do not survive the next experiment. Each one is designed against rather than discovered afterwards.

The full ranked list of labile positions is delivered, so the likely consequence of blocking each one is visible in advance.

Case Studies

The situation

Half-life in human microsomes was under five minutes across every analogue tested.

What the work involved

Atom-level sites of metabolism were predicted for each compound, metabolite structures were proposed for the dominant pathways, and predicted stability was compared against the measured values for calibration.

What came back

A benzylic position was the primary site in every analogue. Fluorination and ring-contraction options were proposed, with the next most labile position identified so the team knew what would surface afterwards.

Illustrative of the shape this work takes. Details are generalised, no client or target is identified, and scope and outcome vary with the system in question.

Questions We Are Asked Before Scoping

Note: ICDMO delivers computational (in silico) services. Results prioritise hypotheses for testing; they do not by themselves establish binding, biological activity, efficacy or safety. All deliverables are for research use only and are not intended for diagnostic or therapeutic use. Downstream experimental work is scoped separately and executed through qualified partners.

Get in Touch
about Metabolic Stability & CYP Prediction

Tell us about the target, the data you hold and the decision the result needs to support. A scientist reviews every enquiry and replies within one business day.

Feasibility reviewed before any scope or price is fixed

Methods, parameters, confidence and limitations in every report

Confidentiality agreement available before data is shared