Extended Data Fig. 2. Overview of macrocycle library hits from the CypD binding selection and JOMBt structure-activity relationships.
a, Two replicates of this selection yielded consistent enrichment of the JO** family of macrocycles. Library hits re-synthesized in DNA-free form resulted in novel CypD inhibitors JOMBt and JOBBt, the starting points of CypD inhibitors developed in this study. b, Structure JOMB, JOGA, and H*JJ macrocycles that enriched well in the DNA-templated macrocycle library selection. JOMB in the trans isomer (JOMBt) exhibits weak prolyl isomerase inhibition. c, Library hits and derivatives of JOMBt and their corresponding prolyl isomerase inhibition IC50 values for CypD. Each listed compound has the JOMBt structure except for the drawn building block substitution. Note, library encoded macrocycles that denote an ‘-A’ nomenclature (JOGBt-A, JOGBc-A, JOBBc-A) include the same primary amide tail shown in JOMBt-A. Values and error bars reflect mean ± s.e.m. of three technical replicates.