Nav1.7 inhibitors for the treatment of chronic pain

Steven J McKerrall; Daniel P Sutherlin

doi:10.1016/j.bmcl.2018.08.007

Na_v1.7 inhibitors for the treatment of chronic pain

Bioorg Med Chem Lett. 2018 Oct 15;28(19):3141-3149. doi: 10.1016/j.bmcl.2018.08.007. Epub 2018 Aug 12.

Authors

Steven J McKerrall¹, Daniel P Sutherlin²

Affiliations

¹ Discovery Chemistry, Genentech Inc, 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: mckerrall.steven@gene.com.
² Discovery Chemistry, Genentech Inc, 1 DNA Way, South San Francisco, CA 94080, USA.

PMID: 30139550
DOI: 10.1016/j.bmcl.2018.08.007

Abstract

The voltage gated sodium channel Na_v1.7 plays an essential role in the transmission of pain signals. Strong human genetic validation has motivated extensive efforts to discover potent, selective, and efficacious Na_v1.7 inhibitors for the treatment of chronic pain. This digest will introduce the structure and function of Na_v1.7 and highlight the wealth of recent developments on a diverse array of Na_v1.7 inhibitors, including optimization of their potency, selectivity, and PK/PD relationships.

Keywords: Na(v)1.7; Pain; SCN9A; Voltage gated sodium channel.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Analgesics / chemistry
Analgesics / pharmacokinetics
Analgesics / pharmacology*
Analgesics / therapeutic use*
Chronic Pain / drug therapy*
Humans
NAV1.7 Voltage-Gated Sodium Channel / drug effects*
Structure-Activity Relationship
Voltage-Gated Sodium Channel Blockers / chemistry
Voltage-Gated Sodium Channel Blockers / pharmacokinetics
Voltage-Gated Sodium Channel Blockers / pharmacology*
Voltage-Gated Sodium Channel Blockers / therapeutic use*

Substances

Analgesics
NAV1.7 Voltage-Gated Sodium Channel
Voltage-Gated Sodium Channel Blockers