Cryo-EM reveals an unprecedented binding site for Na_V1.7 inhibitors enabling rational design of potent hybrid inhibitors.

ABSTRACT: The voltage-gated sodium (Na_V) channel Na_V1.7 has been identified as a potential novel analgesic target due to its involvement in human pain syndromes. However, clinically available Na_V channel-blocking drugs are not selective among the nine Na_V channel subtypes, Na_V1.1-Na_V1.9. Moreover, the two currently known classes of Na_V1.7 subtype-selective inhibitors (aryl- and acylsulfonamides) have undesirable characteristics that may limit their development. To this point understanding of the structure-activity relationships of the acylsulfonamide class of Na_V1.7 inhibitors, exemplified by the clinical development candidate GDC-0310, has been based solely on a single co-crystal structure of an arylsulfo

SUBMITTER: Kschonsak M 

PROVIDER: S-EPMC10112885 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature