GLP and non-GLP hERG IC50s
Cardiac Ion Channel Panel Profiling and IC50 Assays

Determine therapeutic safety margins and proarrhythmia potential
Profiles the most important cardiac ion channels
Compares concentration-response parameters

Benefits:
  • Quantitative profiling
  • Provides mechanisms
  • One week turnaround time

Ion Channel Assay Positive Control

hERG

HEK or CHO cell lines available

GLP Assays:
HCR GLP-PT GLP – protocol conducted at physiological temperature; recommended for IND submissions
HCR GLP-RT – GLP protocol conducted at room temperature
Non-GLP Assays:
GLP-type protocol & report, including concentration pre-testing & GLP-level compound exposure times, but without QAU inspection and auditing required by the GLP protocol 		Cisapride or Terfenadine

Na (Nav1.5)

GLP: conducted at room temperature Non-GLP: conducted at room temp. Lidocaine

L-type & T-type Ca

GLP: conducted at room or physiological temp. Non-GLP: conducted at room temp. Nifedipine

KvLQT1/minK

GLP: conducted at room or physiological temp. Non-GLP: conducted at room temp. Chromanol-293B

Kv4.3, Kv1.5

GLP: conducted at room or physiological temp. Non-GLP: conducted at room temp. Flecainide, 4-AP

IK1, KATP, KACh

GLP: conducted at room or physiological temp. Non-GLP: conducted at room temp. Various

Assay Parameters: GLP hERG IC50 & Other Channels Non-GLP hERG IC50 Channels
Number of concentrations 4 -6 3 - 6
Number of replicates per concentration 3 2 - 3
Positive control (# of measurements) 2 2
Vehicle control (1 concentration N=3) + optional
Assay temp: room (RT) or physiological (PT) RT or PT RT
Concentration pre-testing + +
Protocol & report GLP GLP-type
Cumulative curves + +
Collection of analytical samples + optional
Electronic (pdf) report provided + optional

Optional assays:
  • Dose Solution Analysis – GLP & non-GLP; verify applied concentrations with analytical sample testing of doses
  • Use-dependence analysis
  • Temperature-dependence analysis
Additional options:
  • Additional copies of final report
  • Copies of solution worksheets & data-collection forms
  • Integrated Risk Assessment Summary – dose-response, repolarization, in vivo data compiled in one report
 CRB-IC50 bulletin.pdf