AGI-14100 is a metabolically stable and orally available mIDH1 inhibitor ( IC 50 =6 nM). The pharmacochemical optimization of AGI-14100 is aimed at eliminating hPXR activation, resulting in the final drug candidate AG-120. AG-120 can be used in the study of cancers carrying IDH1 mutations. The discovery and development of AGI-14100 can be used for further studies of mutant isocitrate dehydrogenase 1 ( mIDH1 ) inhibitors.