Screening
Figure 1: Ion channels classes of most interest to survey respondents today
Voltage-Gated: Potassium Channels Voltage-Gated: Sodium Channels
Voltage-Gated: Calcium Channels TRP Channels
Chloride channels
Ligand-Gated: Glutamate activated: NMDA Two Pore Domain Potassium Channels Calcium-Activated Potassium Channels Ion Exchangers
Ligand-Gated: Glutamate activated: AMPA/Kainate Ligand-Gated: P2x
Store-Operated Calcium channels
Ligand-Gated: cys-loop superfamily: nAChR nward Rectifier Potassium Channels Ligand-Gated: cys-loop superfamily: GABA-AR,
Cyclic Nucleotide-Gated Channels Acid-Sensitive Channels
Hyperpolarization-Gated Channels Ligand-Gated: cys-loop superfamily: 5HT-3AR Ligand-Gated: cys-loop superfamily: GlycineR
0% 1% 3% 3%
0% 5% 10% 15% 20% 25% 30% 35% 40% 45% 50% % Responding
© HTStec 2011
10% 10%
9% 9%
8%
7% 7% 7%
6% 4%
Figure 2: Changing interest in ion channels classes (2011 versus 2008)
TRP Channels Chloride channels
Voltage-Gated: Potassium Channels Voltage-Gated: Sodium Channels
Ion Exchangers
Ligand-Gated: Glutamate activated: AMPA/Kainate Cyclic Nucleotide-Gated Channels Ligand-Gated: Glutamate activated: NMDA Ligand-Gated: cys-loop superfamily: 5HT-3AR Store-Operated Calcium channels Ligand-Gated: cys-loop superfamily: GABA-AR Calcium-Activated Potassium Channels Voltage-Gated: Calcium Channels Ligand-Gated: cys-loop superfamily: GlycineR Hyperpolarisation-Gated Channels Ligand-Gated: cys-loop superfamily: nAChR Inward Rectifier Potassium Channels
Acid-Sensitive Channels Ligand-Gated: P2x
© HTStec 2011 -33% -35%
-40% -35% -30% -25% -20% -15% -10% -5% 0% 5% 10% % Change In Normalised Interest (2011 minus 2008)
-7% -11% -13%
-15% -15% -15%
-17% -18% -20%
-25% -24%
-4% -3%
6%
0% 1% 3%
Ion channel classes of greatest interest The class of ion channels of greatest interest to sur- vey respondents today was voltage-gated sodium channels (47% interested). This was very closely followed by voltage-gated potassium channels (47% interested); TRP channels (36% interested), and then voltage-gated calcium channels (34% interested). These classes were distantly followed by chloride channels (14% interested). All other classes including all ligand-gated channels had less than 12% interest to respondents (Figure 1). Figure 2 charts the changing interest in ion chan- nel classes today relative to 2008. This shows that interest had only increased since 2008 with respect to three ion channels classes, ie chloride channels, TRP channels and voltage-gated potassium chan- nels. Interest in voltage-gated sodium channels was unchanged. Interest in all other ion channel classes had decreased since 2008, with the decreases most marked with respect to ligand-gated P2x and acid- sensitive channels (Figure 2).
Ion channel screening activities undertaken in-house
Of the ion channel screening activities undertaken in-house today (2011), the majority of survey respondents were carrying out screening of lead compounds against other specific ion channel tar- gets (59% undertaking), followed by primary screening of ion channels with diversity libraries (53% undertaking) and then safety assessment of lead compounds against specific ion channel liabil- ities (50% undertaking). The least percentage (36%) of survey respondents were carrying out selectivity profiling against a panel of ion channel targets using membrane potential dyes (Figure 3). Figure 4 charts the changing focus of ion channel
46 Drug Discovery World Fall 2011 14% 12% 36% 34% 47% 47%
In March 2011, HTStec undertook the latest update of its Ion Channel Screening Trends 2011 report3. The main objectives of this year’s study were to better understand respondents’ interest and experience of: 1) Ion channels screened, assay technology used and screening metrics generated; 2) the use and purchase of automated patch clamp (APC) systems for ion channel screening; 3) cell requirements for ion channel assays; and 4) the use of outsourced ion channel testing services. In this article we report on the current status of ion channel screening as found in this year’s report, and where consistent report data permits show how the landscape has changed over the past eight years. We also review the latest developments in APC devices and some of the options for out- sourced testing today.
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