5 research outputs found
Cathepsin K inhibitors increase distal femoral bone mineral density in rapidly growing rabbits
Full text linkDiscovery of Aryl Sulfonamides as Isoform-Selective Inhibitors of Na<sub>V</sub>1.7 with Efficacy in Rodent Pain Models
No full textWe report on a novel series of aryl
sulfonamides that act as nanomolar
potent, isoform-selective inhibitors of the human sodium channel hNa<sub>V</sub>1.7. The optimization of these inhibitors is described. We
aimed to improve potency against hNa<sub>V</sub>1.7 while minimizing
off-target safety concerns and generated compound <b>3</b>.
This agent displayed significant analgesic effects in rodent models
of acute and inflammatory pain and demonstrated that binding to the
voltage sensor domain 4 site of Na<sub>V</sub>1.7 leads to an analgesic
effect <i>in vivo</i>. Our findings corroborate the importance
of hNa<sub>V</sub>1.7 as a drug target for the treatment of pain
