na v 1 8  (Alomone Labs)

Journal: The Journal of Comparative Neurology

Article Title: Distribution of Voltage‐Gated Sodium Channels and Scaffolding Proteins on Vestibular Calyx Ending Delineates the Axon Initial Segment

doi: 10.1002/cne.70127

Figure Lengend Snippet: Na V 1.8 antibody labels vestibular afferents and has three different patterns. (A) The heminodes of calyx‐only afferents ( green , color conventions are the same in all panels) are densely labeled with Na V 1.8‐like immunoreactivity ( red ), as seen in both longitudinal section (A) and (B) cross‐section of calyces labeled with calretinin. (C) Occasionally, the inner membrane of a calyx surrounding a type I hair cell, most likely belonging to a dimorphic afferent since these were found in the periphery, is labeled with Na V 1.8. However, because confocal lacks the resolution of electron microscopy, this could also be a type I hair cell membrane. In (D) Na V 1.8 is seen to label the calyx endings of calyces ( arrows ) with relatively light calretinin label (D’). Scale bars: A, C, D = 5 µm, B = 10 µm.

Article Snippet: Na V 1.8 , NeuroMab , 75‐166 RRID:AB_2183861 , , , , X , , Datasheet.

Techniques: Labeling, Membrane, Electron Microscopy

Journal: International Journal of Molecular Sciences

Article Title: Targeting Na v Channels for Pain Relief: Structural Insights and Therapeutic Opportunities

doi: 10.3390/ijms27031180

Figure Lengend Snippet: Topology, gating, and classification of human Na v channels. ( A ) Schematic illustration showing the transmembrane topology of human Na v channels. ( B ) Gating of Na v channels. ( C ) Classification of the nine human Na v isoforms. Top: Phylogenetic tree of human Na v channels, with the three TTX-resistant subtypes (Na v 1.5, Na v 1.8, and Na v 1.9) highlighted in orange. Bottom: Tissue distribution of human Na v channels and representative channelopathies caused by functional disorders of these channels. Na v 1.1 is associated with GEFS+2, EIEE6, ICEGTC, FHM3, and FEB3A; Na v 1.2 with BFIS3, EIEE11, and DS; Na v 1.3 with CPE; Na v 1.4 with multiple neuromuscular disorders including PMC, HOKPP2, HYPP, NKPP, MYOSCN4A, and CMS16; Na v 1.5 with PFHB1A, LQT3, BRGDA1, SSS1, VF1, SIDS, ATRST1, CMD1E, ATFB10, and MEPPC; Na v 1.6 with EIEE13; Na v 1.7 with IEM, PEPD, CIP, DS, SFN, and FEB; Na v 1.8 with SFN; and Na v 1.9 with FEPS3 and HSAN7. See the Abbreviations section for full disease names.

Article Snippet: VX-993 , Vertex Pharmaceuticals , Na v 1.8 , Next-gen Na v 1.8 selective blocker , Phase 2 failed , Vertex is developing additional Na v 1.8 candidates (e.g., VX-993) as follow-ons to VX-548 , [ ] .

Techniques: Functional Assay

Journal: International Journal of Molecular Sciences

Article Title: Targeting Na v Channels for Pain Relief: Structural Insights and Therapeutic Opportunities

doi: 10.3390/ijms27031180

Figure Lengend Snippet: Structural and functional features of Na v 1.8 and its inhibitors. ( A ) Overall structure of Na v 1.8 in complex with the selective inhibitor A-803467 (PDB: 7WE4). ( B ) A-803467 clenches S6 IV of Na v 1.8 beneath the selectivity filter. Inset: Coordination of A-803467. Direct and water-mediated hydrogen bonds (H-bonds) are indicated by red and black dashed lines, respectively. ( C ) ProTxI binds above VSD II of Na v 1.8, with VSD II colored in cyan and ProTxI shown in light-coral surface representation. Inset: Detailed coordination between Na v 1.8 and ProTxI (PDB: 9DBN). ( D ) Predicted binding pose of the clinical inhibitor VX-548, derived from Glide docking in Maestro using the Na v 1.8 structure (PDB: 7WE4). Residues in the S3-4 loop adjacent to VX-548 are highlighted as blue sticks. ( E ) Sequence alignment of the VSD II S3-4 linker. Residues highlighted by the red dashed box are experimentally verified to influence the inhibitory potency of VX-548 on Na v 1.8. ( F ) Top left: Chemical structures of VX-150 and VX-548. Bottom left: Schematic representation of action potentials in DRG neurons before and after VX-548 inhibition, showing that VX-548 markedly decreases both the peak amplitude and the shoulder of action potentials. Right: IC values of VX-548 across human Na v isoforms, measured by patch-clamp recordings. IC values were determined based on inhibition of the peak currents (Ref. ).

Article Snippet: VX-993 , Vertex Pharmaceuticals , Na v 1.8 , Next-gen Na v 1.8 selective blocker , Phase 2 failed , Vertex is developing additional Na v 1.8 candidates (e.g., VX-993) as follow-ons to VX-548 , [ ] .

Techniques: Functional Assay, Binding Assay, Derivative Assay, Sequencing, Inhibition, Patch Clamp

Journal: Molecules

Article Title: Suzetrigine, a Na V 1.8 Inhibitor as a Novel Approach for Pain Therapy—A Medicinal and Chemical Drug Profile

doi: 10.3390/molecules31020358

Figure Lengend Snippet: Chemical structures of selected Na V 1.8 inhibitors.

Article Snippet: In 2014, Vertex Pharmaceuticals introduced the first generation of selective Na V 1.8 blockers with >400-fold greater potency compared to other Na V subtypes [ , ].

Techniques:

Journal: Molecules

Article Title: Suzetrigine, a Na V 1.8 Inhibitor as a Novel Approach for Pain Therapy—A Medicinal and Chemical Drug Profile

doi: 10.3390/molecules31020358

Figure Lengend Snippet: The predicted binding site of LTGO-33 in the extracellular cavity of VSD2 in Na V 1.8, showing key interacting residues (PDB ID: 7WE4). Visualization was performed using Discovery Studio Visualizer 24.1.0.23298 (Dassault Systèmes BIOVIA, San Diego, CA, USA).

Article Snippet: In 2014, Vertex Pharmaceuticals introduced the first generation of selective Na V 1.8 blockers with >400-fold greater potency compared to other Na V subtypes [ , ].

Techniques: Binding Assay