KHS101

KHS101 is a synthetic, blood-brain barrier-penetrant small molecule that acts as an inhibitor of the mitochondrial chaperone heat shock protein family D member 1 (HSPD1, also known as Hsp60) and the transforming acidic coiled-coil-containing protein 3 (TACC3). Originally identified as an inducer of neuronal differentiation in neural progenitor cells, KHS101 has demonstrated significant preclinical efficacy in glioblastoma multiforme (GBM) models. By disrupting HSPD1, KHS101 impairs mitochondrial bioenergetics and aerobic glycolysis, leading to metabolic energy depletion and selective tumor cell death (lethal autophagy and apoptosis) in diverse GBM subtypes without affecting non-cancerous brain cells. It also destabilizes TACC3, suppressing cancer cell stemness, epithelial-mesenchymal transition (EMT), and migration.

Other names

N4-(2-methylpropyl)-N2-[(2-phenyl-4-thiazolyl)methyl]-2,4-pyrimidinediamine