Hope everyone had a fantastic Christmas weekend. Last month there were quite a few large small molecules, including three macrocycles. Quite a few of these molecules would’ve made for a decent synthesis PhD project! Some highlights include a cryo-EM structure for Chugai/Lilly’s GLP-1R agonist, a Ra Pharma mRNA display screen yielding a PCSK9 PPI inhibitor, and a crystal structure of a BTK-degrader-cIAP ternary complex from Pfizer. Enjoy!