In the article 'Ion channels return to centre stage in pain drug discovery' published in Nature, Metrion and the Lieber Institute for Brain Development explore the developments behind this resurgence, the opportunities presented by other sodium channel targets, and the importance of scientific expertise and collaboration in drug discovery.
The approval of suzetrigine, an analgesic targeting the voltage-gated sodium channel NaV1.8, represents an important development in pain drug discovery.
NaV1.8 was identified in the mid-1990s and attracted considerable interest because of its expression predominantly in peripheral sensory neurons involved in pain signalling. Its potential as a therapeutic target also offered an alternative approach to opioid-based pain treatments.
However, ion channels have historically been considered difficult drug discovery targets. Achieving selectivity between closely related channel subtypes has been challenging, particularly where drug-binding sites are conserved across channel families. Earlier limitations in high-throughput screening technologies also restricted the ability to investigate ion channel pharmacology at scale.
Suzetrigine's approval demonstrates that compounds with high levels of selectivity between closely related ion channels can be developed, renewing confidence in this approach to pain drug discovery.
While interest in ion channel targets declined across parts of the pharmaceutical industry, technologies for studying their pharmacology continued to develop.
Advances in automated electrophysiology have improved the ability to investigate ion channel activity at scale, creating new opportunities for drug discovery programmes.
High-throughput electrophysiology is increasingly being used earlier in the discovery process to characterise how compounds affect ion channel function. These functional measurements can provide information to support medicinal chemistry decisions and guide further compound development.
However, the significance of these advances extends beyond the availability of screening technologies. Appropriate experimental design and specialist scientific expertise remain important for investigating ion channel pharmacology and interpreting the resulting data.
Although suzetrigine has been approved for acute pain, its efficacy in chronic pain remains under investigation.
Chronic pain represents a substantial clinical need and can persist as a disease state in its own right. Demonstrating efficacy in this setting remains an important question for ion channel-targeted pain therapeutics.
Researchers are also continuing to investigate other peripheral ion channel targets and the potential of different therapeutic approaches, including combinations of compounds targeting distinct channels.
The success of NaV1.8 inhibition has therefore renewed interest in a broader range of ion channel targets, although further research is needed to establish their therapeutic potential.
Beyond NaV1.8, other voltage-gated sodium channels are attracting renewed attention, particularly NaV1.7 and NaV1.9.
NaV1.9 is expressed in pain-sensing neurons and contributes to the regulation of neuronal firing. Historically, difficulties expressing this channel in heterologous systems have limited research opportunities. Improvements in cellular reagents are now helping researchers investigate its pharmacology more extensively.
NaV1.7 also remains an important area of interest in pain drug discovery. Researchers are exploring whether combining blockers of different sodium channel subtypes could produce additive effects.
These approaches offer further avenues for investigation, although their potential benefits will need to be established through continued research.
In the Nature article, Metrion's Chief Scientific Officer, Eddy Stevens PhD, and Mike Poslusney PhD, Medicinal Chemist at the Lieber Institute for Brain Development, share their perspectives on the renewed interest in ion channel drug discovery.
Mike Poslusney, who has collaborated with Metrion since 2018, highlights the value of a collaborative approach in which scientists work together to address research questions rather than simply delivering experimental data.
This approach is also central to Metrion's philosophy. Combining electrophysiology expertise with carefully designed experiments enables research teams to investigate specific scientific questions and generate data that can inform drug discovery decisions.
The approval of a selective NaV1.8 inhibitor has renewed confidence in ion channels as targets for pain therapeutics. Alongside continued advances in electrophysiology and cellular reagents, this is encouraging further investigation of targets that have presented difficulties for drug discovery in the past.
However, important questions remain, particularly around demonstrating efficacy in chronic pain and establishing the therapeutic potential of other ion channel targets.
As research progresses, specialist scientific expertise, robust experimental approaches and collaboration will remain important in investigating how promising ion channel biology might translate into effective therapeutics.
Read about unlocking ion channel opportunities in drug discovery through electrophysiology.
In the article 'Ion channels return to centre stage in pain drug discovery' published in Nature, Metrion and the Lieber Institute for Brain Development explore the developments behind this resurgence, the opportunities presented by other sodium channel targets, and the importance of scientific expertise and collaboration in drug discovery.
The approval of suzetrigine, an analgesic targeting the voltage-gated sodium channel NaV1.8, represents an important development in pain drug discovery.
NaV1.8 was identified in the mid-1990s and attracted considerable interest because of its expression predominantly in peripheral sensory neurons involved in pain signalling. Its potential as a therapeutic target also offered an alternative approach to opioid-based pain treatments.
However, ion channels have historically been considered difficult drug discovery targets. Achieving selectivity between closely related channel subtypes has been challenging, particularly where drug-binding sites are conserved across channel families. Earlier limitations in high-throughput screening technologies also restricted the ability to investigate ion channel pharmacology at scale.
Suzetrigine's approval demonstrates that compounds with high levels of selectivity between closely related ion channels can be developed, renewing confidence in this approach to pain drug discovery.
While interest in ion channel targets declined across parts of the pharmaceutical industry, technologies for studying their pharmacology continued to develop.
Advances in automated electrophysiology have improved the ability to investigate ion channel activity at scale, creating new opportunities for drug discovery programmes.
High-throughput electrophysiology is increasingly being used earlier in the discovery process to characterise how compounds affect ion channel function. These functional measurements can provide information to support medicinal chemistry decisions and guide further compound development.
However, the significance of these advances extends beyond the availability of screening technologies. Appropriate experimental design and specialist scientific expertise remain important for investigating ion channel pharmacology and interpreting the resulting data.
Although suzetrigine has been approved for acute pain, its efficacy in chronic pain remains under investigation.
Chronic pain represents a substantial clinical need and can persist as a disease state in its own right. Demonstrating efficacy in this setting remains an important question for ion channel-targeted pain therapeutics.
Researchers are also continuing to investigate other peripheral ion channel targets and the potential of different therapeutic approaches, including combinations of compounds targeting distinct channels.
The success of NaV1.8 inhibition has therefore renewed interest in a broader range of ion channel targets, although further research is needed to establish their therapeutic potential.
Beyond NaV1.8, other voltage-gated sodium channels are attracting renewed attention, particularly NaV1.7 and NaV1.9.
NaV1.9 is expressed in pain-sensing neurons and contributes to the regulation of neuronal firing. Historically, difficulties expressing this channel in heterologous systems have limited research opportunities. Improvements in cellular reagents are now helping researchers investigate its pharmacology more extensively.
NaV1.7 also remains an important area of interest in pain drug discovery. Researchers are exploring whether combining blockers of different sodium channel subtypes could produce additive effects.
These approaches offer further avenues for investigation, although their potential benefits will need to be established through continued research.
In the Nature article, Metrion's Chief Scientific Officer, Eddy Stevens PhD, and Mike Poslusney PhD, Medicinal Chemist at the Lieber Institute for Brain Development, share their perspectives on the renewed interest in ion channel drug discovery.
Mike Poslusney, who has collaborated with Metrion since 2018, highlights the value of a collaborative approach in which scientists work together to address research questions rather than simply delivering experimental data.
This approach is also central to Metrion's philosophy. Combining electrophysiology expertise with carefully designed experiments enables research teams to investigate specific scientific questions and generate data that can inform drug discovery decisions.
The approval of a selective NaV1.8 inhibitor has renewed confidence in ion channels as targets for pain therapeutics. Alongside continued advances in electrophysiology and cellular reagents, this is encouraging further investigation of targets that have presented difficulties for drug discovery in the past.
However, important questions remain, particularly around demonstrating efficacy in chronic pain and establishing the therapeutic potential of other ion channel targets.
As research progresses, specialist scientific expertise, robust experimental approaches and collaboration will remain important in investigating how promising ion channel biology might translate into effective therapeutics.
Read about unlocking ion channel opportunities in drug discovery through electrophysiology.
In the article 'Ion channels return to centre stage in pain drug discovery' published in Nature, Metrion and the Lieber Institute for Brain Development explore the developments behind this resurgence, the opportunities presented by other sodium channel targets, and the importance of scientific expertise and collaboration in drug discovery.
The approval of suzetrigine, an analgesic targeting the voltage-gated sodium channel NaV1.8, represents an important development in pain drug discovery.
NaV1.8 was identified in the mid-1990s and attracted considerable interest because of its expression predominantly in peripheral sensory neurons involved in pain signalling. Its potential as a therapeutic target also offered an alternative approach to opioid-based pain treatments.
However, ion channels have historically been considered difficult drug discovery targets. Achieving selectivity between closely related channel subtypes has been challenging, particularly where drug-binding sites are conserved across channel families. Earlier limitations in high-throughput screening technologies also restricted the ability to investigate ion channel pharmacology at scale.
Suzetrigine's approval demonstrates that compounds with high levels of selectivity between closely related ion channels can be developed, renewing confidence in this approach to pain drug discovery.
While interest in ion channel targets declined across parts of the pharmaceutical industry, technologies for studying their pharmacology continued to develop.
Advances in automated electrophysiology have improved the ability to investigate ion channel activity at scale, creating new opportunities for drug discovery programmes.
High-throughput electrophysiology is increasingly being used earlier in the discovery process to characterise how compounds affect ion channel function. These functional measurements can provide information to support medicinal chemistry decisions and guide further compound development.
However, the significance of these advances extends beyond the availability of screening technologies. Appropriate experimental design and specialist scientific expertise remain important for investigating ion channel pharmacology and interpreting the resulting data.
Although suzetrigine has been approved for acute pain, its efficacy in chronic pain remains under investigation.
Chronic pain represents a substantial clinical need and can persist as a disease state in its own right. Demonstrating efficacy in this setting remains an important question for ion channel-targeted pain therapeutics.
Researchers are also continuing to investigate other peripheral ion channel targets and the potential of different therapeutic approaches, including combinations of compounds targeting distinct channels.
The success of NaV1.8 inhibition has therefore renewed interest in a broader range of ion channel targets, although further research is needed to establish their therapeutic potential.
Beyond NaV1.8, other voltage-gated sodium channels are attracting renewed attention, particularly NaV1.7 and NaV1.9.
NaV1.9 is expressed in pain-sensing neurons and contributes to the regulation of neuronal firing. Historically, difficulties expressing this channel in heterologous systems have limited research opportunities. Improvements in cellular reagents are now helping researchers investigate its pharmacology more extensively.
NaV1.7 also remains an important area of interest in pain drug discovery. Researchers are exploring whether combining blockers of different sodium channel subtypes could produce additive effects.
These approaches offer further avenues for investigation, although their potential benefits will need to be established through continued research.
In the Nature article, Metrion's Chief Scientific Officer, Eddy Stevens PhD, and Mike Poslusney PhD, Medicinal Chemist at the Lieber Institute for Brain Development, share their perspectives on the renewed interest in ion channel drug discovery.
Mike Poslusney, who has collaborated with Metrion since 2018, highlights the value of a collaborative approach in which scientists work together to address research questions rather than simply delivering experimental data.
This approach is also central to Metrion's philosophy. Combining electrophysiology expertise with carefully designed experiments enables research teams to investigate specific scientific questions and generate data that can inform drug discovery decisions.
The approval of a selective NaV1.8 inhibitor has renewed confidence in ion channels as targets for pain therapeutics. Alongside continued advances in electrophysiology and cellular reagents, this is encouraging further investigation of targets that have presented difficulties for drug discovery in the past.
However, important questions remain, particularly around demonstrating efficacy in chronic pain and establishing the therapeutic potential of other ion channel targets.
As research progresses, specialist scientific expertise, robust experimental approaches and collaboration will remain important in investigating how promising ion channel biology might translate into effective therapeutics.
Read about unlocking ion channel opportunities in drug discovery through electrophysiology.