The March 2021 edition of Drug Hunter‘s Small Molecules of the Month series contains several small molecule clinical candidates as well as pre-clinical small molecules with interesting structures or mechanisms. Among the highlights are LSN3318839, a molecular glue that binds both GLP-1R receptor its endogenous GLP peptide, a P-gp inhibitor intended to induce a drug-drug interaction (DDI), and two non-traditional zinc binders including a hydantoin and a phosphinic acid. There are numerous chemistry rule-breakers here, including an oral brain penetrant compound with 5 rings, a compound with a predicted human oral dose of 15 mg with 6 hydrogen bond donors (HBDs) and 6 rings, and a venetoclax prodrug that enables a 100 mg pill.