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, cell reporter) measure the cellular response and distinguish agonists from antagonists. InVEST panels use binding for most targets and functional assays where mechanism changes clinical interpretation, such as ion channels and select GPCRs and nuclear receptors.

InVEST33 is a bridge panel for compounds already screened in InVEST44. It contains the 33 InVEST77 targets that InVEST44 does not cover: 19 kinases at 1 mM ATP, 6 GPCRs, 3 nuclear receptors, 2 proteases, BRD4, nAChR α1 and GAT1. Together, InVEST44 and InVEST33 deliver the full InVEST77 profile plus neuronal nAChR α4β2, without re-screening any target.

Match the panel to your stage. Core: InVEST18 for hit triage, or InVEST44 for the Bowes industry standard at hit-to-lead. Extended: InVEST59 for kinase-weighted selectivity during lead optimization. Comprehensive: InVEST77, aligned with Brennan et al. (2024), for candidate selection. If you have already run InVEST18 or InVEST44, add InVEST59 or InVEST33 to reach InVEST77 without repeating targets.

InVEST44 is the 44-target panel defined by AstraZeneca, GSK, Novartis and Pfizer (Bowes et al., 2012). InVEST18, InVEST59 and InVEST77 are built on the target sets in the IQ DruSafe survey of 18 companies (Brennan et al., 2024), which proposed a 77-target panel as the modern standard. InVEST33 is the set of InVEST77 targets not covered by InVEST44.

The industry-standard 44-target panel (Bowes et al., 2012) includes 24 GPCRs (including serotonin, dopamine, adrenergic, opioid, muscarinic and histamine receptors), 8 ion channels (hERG, Nav1.5, Cav1.2, KCNQ1/KCNE1, GABA-A, 5-HT3, NMDA and nAChR α4/β2), 6 enzymes (AChE, COX1, COX2, MAO-A, PDE3A and PDE4D2), 3 transporters (NET, DAT and SERT), 2 nuclear receptors (androgen and glucocorticoid) and 1 kinase (LCK). Extended panels add kinases, nuclear receptors, proteases, BRD4 and additional GPCRs and transporters.

hERG (KCNH2) encodes the cardiac potassium channel responsible for ventricular repolarization. hERG inhibition prolongs the QT interval and increases the 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 at every tier, from 18 targets to 77. Comprehensive profiling takes no longer than a core screen. Monthly screening runs enable predictable scheduling; expedited timelines are available for urgent programs.

Single-concentration screening (typically 10 µM; custom concentrations on request) is cost-effective for early-stage profiling across many targets. Dose-response IC50/EC50 determination is appropriate for confirmed hits that need 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 to 5 mM. Running kinase assays at 1 mM ATP provides translationally relevant IC50 values and reduces false positives that lack activity under cellular conditions. All InVEST kinase targets are profiled at 1 mM ATP.

Both cover the same 44 consensus targets from Bowes et al. (2012). While SafetyScreen44 primarily uses biochemical radioligand binding and enzymatic assays, InVEST44 delivers in 10 business days from a single US facility (Malvern, PA) and provides 7 functional cell-based assays for GPCRs, nuclear receptors and ion channels in addition to biochemical and enzymatic assays. Ion channel data comes from whole-cell patch clamp electrophysiology for Cav1.2, KCNQ1/minK and Nav1.5, in contrast to the biochemical assays SafetyScreen44 uses for Cav1.2, pan Nav and pan Kv channels. Concentration-response curves are offered for any target. Extending to the 77-target standard takes one bridge panel, InVEST33.

FDA guidance recommends screening CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4 for inhibition. CYP3A4 metabolizes more than 50% of marketed drugs. Time-dependent inhibition (TDI) screening identifies mechanism-based inhibitors with elevated DDI risk. InVEST CYP covers 14 isoforms with reversible inhibition and TDI 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/minK (IKs) and others for expanded assessment. InVEST includes hERG (fluorescence polarization assay, with patch clamp follow-up as needed) and Nav1.5, Cav1.2 and KCNQ1 via manual patch clamp, the regulatory gold standard for studying ion channel inhibition.

Yes. Over 100 individual targets are available across the InVEST, CYP and PDE panels. Send 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.