Fig. 8.

The apelin receptor structure from PDBID 5VBL (Ma et al., 2017) with docked poses of five series of apelin agonists. The apelin receptor residues, W²⁴, W⁸⁵, Y⁹³, K²⁶⁸, and Y²⁷¹ are labeled and displayed as gray space filling. The structure of the four C-terminal residues of the apelin analog from PDBID 5VBL are displayed as gray sticks. The receptor and peptide are overlaid with docked poses of an Amgen (violet balls and sticks), a Bristol-Myers Squibb (yellow balls and sticks), an RTI International (orange balls and sticks), a Sanford-Burnham (magenta balls and sticks), and a Sanofi (cyan balls and sticks) small molecule apelin agonist. Only polar hydrogens are shown. Structures were derived from the following patents: Amgen (Chen et al., 2017), Bristol-Myers Squibb (Myers et al., 2017), RTI International (Narayanan et al., 2016), Sanford-Burnham (Pinkerton and Smith, 2015), and Sanofi (Hachtel et al., 2014). Pinkerton and Smith (2015) confirmed the Sanford-Burnham apelin compounds were selective vs. the angiotensin II receptor (AT₁), the most closely related GPCR, with no significant off target binding.