JX57

JX57 is a chlorpromazine derivative developed as a small molecule therapeutic with notable anticancer properties, especially against endometrial cancer. It acts by directly targeting **glucose-regulated protein 75 kD (GRP75/HSPA9/Mortalin)**, a mitochondrial chaperone protein that plays a pivotal role in endoplasmic reticulum-mitochondria calfcium signaling and bioenergetics. JX57 disrupts the structural integrity of the mitochondria-associated endoplasmic reticulum membrane (MAM) by inhibiting the GRP75–IP3R complex, leading to impaired mitochondrial calcium homeostasis, mitochondrial dysfunction, reduced ATP production, triggering a bioenergetic crisis, and activating AMP-activated protein kinase (AMPK). Pharmacologically, JX57 displays high oral bioavailability (94.3%) and a strong plasma protein binding rate (99.16%). It exhibits greater potency against endometrial cancer than its parent compound, chlorpromazine, and related derivatives, with fewer extrapyramidal side effects.