Development of ProTx-II Analogues as Highly Selective Peptide Blockers of Nav1.7 for the Treatment of Pain.
J Med Chem
; 65(1): 485-496, 2022 01 13.
Article
en En
| MEDLINE
| ID: mdl-34931831
Inhibitor cystine knot peptides, derived from venom, have evolved to block ion channel function but are often toxic when dosed at pharmacologically relevant levels in vivo. The article describes the design of analogues of ProTx-II that safely display systemic in vivo blocking of Nav1.7, resulting in a latency of response to thermal stimuli in rodents. The new designs achieve a better in vivo profile by improving ion channel selectivity and limiting the ability of the peptides to cause mast cell degranulation. The design rationale, structural modeling, in vitro profiles, and rat tail flick outcomes are disclosed and discussed.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Dolor
/
Venenos de Araña
/
Bloqueadores de los Canales de Sodio
/
Canal de Sodio Activado por Voltaje NAV1.7
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
2022
Tipo del documento:
Article