In Vitro Safety Pharmacology Profiling

Binding assays (radioligand displacement, fluorescence polarization) measure whether a compound occupies a target. Functional assays (FLIPR calcium flux, patch clamp electrophysiology, reporter gene) measure cellular response—distinguishing agonists from antagonists. InVEST panels use binding for most targets and functional assays where mechanism of action changes clinical interpretation, such as ion channels and select GPCRs.

The industry-standard 44-target panel (Bowes et al., 2012) includes 24 GPCRs (serotonin, dopamine, adrenergic, opioid, muscarinic, histamine receptors), 8 ion channels (hERG, Nav1.5, Cav1.2, KCNQ1/KCNE1, GABA(A), nAChR), 7 enzymes (AChE, COX1/2, MAO-A, PDE3A, PDE4D, LCK), 3 transporters (NET, DAT, SERT), and 2 nuclear receptors (androgen, glucocorticoid). Extended panels (59–77 targets) add kinases, additional GPCRs, and transporters.

hERG (KCNH2) encodes the cardiac potassium channel responsible for ventricular repolarization. hERG inhibition prolongs QT interval and increases risk of torsades de pointes arrhythmia—a leading cause of drug withdrawals. ICH S7B guidelines require hERG assessment. InVEST panels include hERG binding (fluorescence polarization) with functional patch clamp confirmation available for hits.

InVEST panels deliver data in 10 business days regardless of panel size (18, 44, 59, or 77 targets). This compares to 3–6 week turnaround at many providers. Monthly screening runs enable predictable scheduling; expedited timelines available for urgent programs.

Single-concentration screening (typically 10 µM, custom concentration can be requested) is cost-effective for early-stage profiling across many targets. Dose-response IC50/EC50 determination is appropriate for confirmed hits requiring quantitative potency data. InVEST offers both formats for all targets—screen broadly first, then generate curves on flagged interactions.

Most kinase inhibitors are ATP-competitive. Assays run at low ATP (Km conditions) overestimate potency because less ATP competes for the binding site. Physiological intracellular ATP is 1–5 mM. Running kinase assays at 1mM ATP provides translationally relevant IC50 values and reduces false positives that lack activity under cellular conditions. All InVEST kinase targets are profiled at 1mM ATP.

Both cover the same 44 consensus targets derived from Bowes et al. (2012). InVEST44 delivers in 10 business days from a single US facility (Malvern, PA), includes functional assays for ion channels and select GPCRs, and offers dose-response for any target. Panel selection is straightforward with no overlapping legacy nomenclature.

FDA guidance recommends screening CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4 for inhibition. CYP3A4 metabolizes >50% of marketed drugs. Time-dependent inhibition (TDI) screening identifies mechanism-based inhibitors with elevated DDI risk. CYP induction assessment (1A2, 2B6, 3A4) is required when inhibition or structural alerts are present. InVEST CYP covers 14 isoforms with reversible, TDI, and induction options.

The Comprehensive in vitro Proarrhythmia Assay (CiPA) paradigm evaluates hERG (IKr), Nav1.5 (INa), and Cav1.2 (ICa,L) as core channels, with KCNQ1/KCNE1 (IKs), Kir2.1 (IK1), and others for expanded assessment. InVEST includes hERG, Nav1.5, Cav1.2, and KCNQ1 via manual patch clamp. Automated patch clamp (IonFlux Mercury 16) available for higher-throughput screening.

Yes. Over 100 individual targets are available beyond standard panels. Contact with your target list to confirm availability and pricing. Custom panels can combine standard InVEST targets with additional receptors, enzymes, or kinases specific to your therapeutic area.