LY345899 exhibited potent antitumoractivity in colorectal cancer in vivo7 butwas poorly selective among MTHFD isozymes and an even more potentinhibitor of MTHFD1 (IC50 = 96 nM).14 Raze Therapeutics reported a new class of MTHFD2 inhibitorsbased on a caffeine scaffold (Figure 1).15,16 Kawai et al. disclosed a seriesof sulfonamide derivatives incorporating a coumarin skeleton (Figure 1). The gene discussed is MTHFD1; the disease is colorectal cancer.