NOTCH1 and adrenal cortex carcinoma: Notably, PRMT5 inactivation by either PRT543 or PRT811 (another highly selective, brain penetrant PRMT5 inhibitor) resulted in a comparable inhibitory profile in organoid models with wild-type or mutated NOTCH1. This was supported by our in vivo analysis (demonstrating that PRT543 induced anti-tumor activity in PDXs irrespective of NOTCH1 alteration status), and further confirmed by the recent phase-I clinical trial that assessed safety and efficacy of PRT543 in patients with recurrent/metastatic ACC [45].