Screening
majority (25% choosing either option) would con- sider it if the cost per data point equals the current cost of primary screening (FLIPR costs), or if they see that a direct assay will increase compound spe- cific information significantly. A further 17% indicated they would consider if the target requires a technology with high data quality read- out and 16% if the timeline and throughput for such a screen would equal our current primary screening method (eg FLIPR). That left 17% who indicated there were no circumstances where they would consider it (Figure 9).
What represents quality in APC measurements?
What represents best quality in APC measurements to survey respondents is presented in Figure 10. The biggest proportion (35%) of survey respon- dents thought giga-seal resistances represents best quality in APC measurements. This was very close- ly followed by stable pharmacological responses and then stable whole-cell conditions (32% responding) and then stable whole-cell conditions (27% responding). Only a small minority (3% or 4%) of respondents thought temperature control or Rs compensation represented best quality in APC measurements (Figure 10).
Use of more relevant cell backgrounds Survey respondents most want to use primary cells or more relevant cell backgrounds for ion channel testing in hits-to-leads (lead optimisation) (50% wanting); compound profiling (47% wanting), and then safety assessment (non-compliant) (31% wanting). Survey respondents were least interested in using primary cells or more relevant cell back- grounds in primary screening/HTS (only 15% wanting) (Figure 11).
Latest developments in ion channel screening
The following snapshots provide details of how various vendors support work on ion channel screening through provision of new automated patch clamp instruments and testing services.
BioFocus (
www.biofocus.com) is a leading provider of drug discovery services. With compre- hensive capabilities, from target identification and validation to candidate drug nomination, BioFocus works in partnership with clients to deliver project milestones. BioFocus’ ion channel team and its array of core technologies provide breadth and throughput to perform high-throughput screening for voltage- and ligand-gated, multimodal and
Drug Discovery World Fall 2011
Figure 9: When respondents would use an APC system for primary screening
If we see that a direct assay will increase compound If the cost per datapoint equals the current cost
If the target requires a technology with high data quality readout
No circumstance, would never consider, or N/A
If the timeline and throughput for such a screen would equal our current primary screening method (eg FLIPR)
0% © HTStec 2011
Figure 10: What most represents best quality in APC measurements
Stable pharmacological responses Gigaseal resistances
Stable whole-cell conditions Temperature control Rs compensation 0% © HTStec 2011 3%
5% 10% 15% 20% 25% 30% 35% 40% % Responding
4% 27% 35% 32%
specific information significantly of primary screening (FLIPR costs)
17% 17%
16%
5% 10% 15% 20% 25% 30% % Responding
25% 25%
Figure 11: Where respondents most want to use primary cells or more relevant cell backgrounds in ion channel testing
Backgrounds In Ion Channel Testing Hits-to-leads (lead optimisation)
Safety assessment (compliant) Safety assessment (non-compliant) Compound profiling
Primary screening/HTS Secondary screening
22% 15%
0% 5% 10% 15% 20% 25% 30% 35% 40% 45% 50% 55% % Responding
© HTStec 2011 47% 31% 26% 50%
Table 1: Ion channel primary screening metrics over the past eight years
Table 1. Ion Channel Primary Screening Metrics Over The Past 8 Years 2004
2005 Large Pharma
MEDIAN No. Screens/Year 445443 MEDIAN No. Data Points/Screen
250K-500K 250K-500K 500K-1M 500K-1M 250K-500K 250K-500K
Small/Medium Pharma & Biotech MEDIAN No. Screens/Year 233222 MEDIAN No. Data Points/Screen
50K-100K 100K-250K 100K-250K 50K-100K 10K-50K 10K-50K 2007 2008 2009 2011
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