Novel lipidated cgrp peptide antagonists for the treatment of migraine and pain

There is high interest in blocking the actions of the neuropeptide calcitonin gene-related peptide (CGRP) for the treatment of migraine, other headache disorders, and distinct classes of pain. Small molecule antagonists and antibodies that target either CGRP itself or a CGRP receptor have been developed for clinical use. However, there are also opportunities to develop CGRP peptide antagonists. Peptide-based drugs often face difficulties with rapid degradation and clearance in circulation. However, attachment of fatty acyl residues can be a successful strategy to extend peptide half-life in vivo. Here, we developed a small library of lipidated analogues of CGRP peptide fragments and determined their pharmacology in vitro.