CRH and stress-related disorder: The antagonistic properties of M43 are attributed to its interaction with residues in the TM3, TM5, and TM6 of CRF1R. These interactions block activation-associated structural rearrangements of the CRF1R. The pharmacological properties of M43 render it an optimal lead compound in the rational design of novel non-peptide CRF antagonists, which will enrich the pharmaceutical arsenal against CAH and stress-related disorders.