Temporary Cell Cycle Arrest in Human Scalp Hair Follicles and Their Epithelial Stem Cells by ALRN-6924: A Novel Strategy to Selectively Protect p53-Wildtype Cells Against Paclitaxel-Induced Alopecia

ALRN-6924, a dual inhibitor of MDM2/MDMX, was found to protect human scalp hair follicles (HFs) and their epithelial stem cells (SCs) from paclitaxel (PTX)-induced damage by inducing transient cell cycle arrest in p53-wild-type cells. This protection was evidenced by increased p21+ cells, reduced melanin clumps, apoptosis, pathological mitosis, and DNA damage in treated HFs. ALRN-6924 did not promote catagen development, suggesting it may prevent or reduce both acute and permanent chemotherapy-induced alopecia (CIA) without affecting cancer cells.