Open AccessChallenges and Opportunities for Therapeutics Targeting the Voltage-Gated Sodium Channel Isoform NaV1.7
Author(s) -
John V. Mulcahy,
Hassan Pajouhesh,
Jacob T. Beckley,
Anton Delwig,
J. Du Bois,
John C. Hunter
Publication year - 2019
Publication title -
journal of medicinal chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.01
H-Index - 261
eISSN - 1520-4804
pISSN - 0022-2623
DOI - 10.1021/acs.jmedchem.8b01906
Subject(s) - sodium channel , sodium channel blocker , chemistry , pharmacology , analgesic , ion channel , drug discovery , perspective (graphical) , gene isoform , neuroscience , computational biology , medicine , sodium , psychology , biochemistry , receptor , computer science , gene , biology , organic chemistry , artificial intelligence
Voltage-gated sodium ion channel subtype 1.7 (Na V 1.7) is a high interest target for the discovery of non-opioid analgesics. Compelling evidence from human genetic data, particularly the finding that persons lacking functional Na V 1.7 are insensitive to pain, has spurred considerable effort to develop selective inhibitors of this Na + ion channel target as analgesic medicines. Recent clinical setbacks and disappointing performance of preclinical compounds in animal pain models, however, have led to skepticism around the potential of selective Na V 1.7 inhibitors as human therapeutics. In this Perspective, we discuss the attributes and limitations of recently disclosed investigational drugs targeting Na V 1.7 and review evidence that, by better understanding the requirements for selectivity and target engagement, the opportunity to deliver effective analgesic medicines targeting Na V 1.7 endures.