Discovery of Clinical Candidate AZD5462, a Selective Oral Allosteric RXFP1 Agonist for Treatment of Heart Failure

Granberg, Kenneth L.; Sakamaki, Shigeki; Larsson, Niklas; Bergström, Fredrik; Fuchigami, Ryuichi; Niwa, Yasuki; Ryberg, Erik; Backmark, Anna; Kato, Harutoshi; Miyazaki, Shiki; Iguchi, Kaori; Sakamoto, Toshiaki; Persson, Mikael; Idei, Akiko; Prieto Garcia, Luna; Villar, Inmaculada C.; Gradén, Henrik; Bergonzini, Giulia; Arvidsson, Torbjörn; Fujita, Takuya; Althage, Magnus; Ulander, Johan; Kimura, Junpei; Yoneda, Hikaru; Fjellström, Ola; Mochida, Hideki; Lal, Mark

doi:10.1021/acs.jmedchem.3c02184

Discovery of Clinical Candidate AZD5462, a Selective Oral Allosteric RXFP1 Agonist for Treatment of Heart Failure

Optimization of the highly potent and selective, yet metabolically unstable and poorly soluble hRXFP1 agonist AZ7976 led to the identification of the clinical candidate, AZD5462. Assessment of RXFP1-dependent cell signaling demonstrated that AZD5462 activates a highly similar panel of downstream …