Targeting the minor pocket of C5aR for the rational design of an oral allosteric inhibitor for inflammatory and neuropathic pain relief

Moriconi, A.; Cunha, T.; Souza, G.; Lopes, A.; Cunha, F.; Carneiro, V.; Pinto, L.; Brandolini, L.; Aramini, A.; Bizzarri, C.; Bianchini, G.; Beccari, A.; Fanton, M.; Bruno, A.; Costantino, G.; Bertini, R.; Galliera, E.; Locati, M.; Ferreira, S.; Teixeira, M.; Allegretti, M.

doi:10.1073/pnas.1417365111

Chronic pain resulting from inflammatory and neuropathic disorders causes considerable economic and social burden. In particular in the orthopaedic field, musculoskeletal pain is one of the most predominant kinds of chronic pain and its prevalence is increasing. Pharmacological therapies currently available for certain types of pain are only partially effective and may cause severe adverse side effects. Pharmacological results of this study support that the allosteric blockade of the C5aR represents a highly promising therapeutic approach to control chronic inflammatory and neuropathic pain.

Targeting the minor pocket of C5aR for the rational design of an oral allosteric inhibitor for inflammatory and neuropathic pain relief / Moriconi, A.; Cunha, T.; Souza, G.; Lopes, A.; Cunha, F.; Carneiro, V.; Pinto, L.; Brandolini, L.; Aramini, A.; Bizzarri, C.; Bianchini, G.; Beccari, A.; Fanton, M.; Bruno, A.; Costantino, G.; Bertini, R.; Galliera, E.; Locati, M.; Ferreira, S.; Teixeira, M.; Allegretti, M.. - In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. - ISSN 0027-8424. - 111:47(2014), pp. 16937-16942. [10.1073/pnas.1417365111]