Transient receptor potential cation channel subfamily V member 1 (TRPV1), also known as the capsaicin receptor has raised enormous interest as a novel drug target against pain. Activation of TRPV1 induces an initial burning effect, but prolonged administration of TRPV1 agonists show analgesic effects due to desensitization of the receptor. TRPV1 antagonists, however, provides another promising approach for pain relief by effectively blocking TRPV1 opening.The recently discovered crystal structure of the ankyrin repeat domain (ARD) of TRPV1 has revealed an allosteric modulatory site. It was suggested that ATP and calmodulin modulates TRPV1 activity by binding to this cavity. Thus, this allosteric site provides an interesting target for developing novel TRPV1 modulators that can provide an alternative treatment strategy compared to traditional TRPV1 agonist/antagonist therapies. Furthermore, such modulators might serve as enhancers of orthosteric TRPV1 ligands.We performed a structure-based virtual screen targeting the ARD of TRPV1. Several interesting virtual hits have been selected for further investigations. In vitro testing of these compounds is underway.Virtual screening was conducted at mcule.com. The screening workflow and the applied tools are accessible at mcule.com for everyone who is interested. Mcule provides several other virtual screening tools and customizable screening workflows on the web.

Identifying TRPV1 modulators by structure-based virtual screening: A case study of using drug discovery tools at mcule.com

244th National Meeting (2012)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.