WNK1 inhibitor

WNK1 inhibitors are a class of small molecule therapeutics designed to target With-no-Lysine (K) kinase 1 (WNK1), a serine/threonine kinase traditionally known for its role in ion homeostasis and blood pressure regulation via the SPAK/OSR1 signaling pathway. Recent research has identified WNK1 as a potential therapeutic target in oncology, particularly in Acute Myeloid Leukemia (AML) and Glioblastoma (GBM). In AML, WNK1 acts as a regulator of differentiation arrest; its inhibition promotes myeloid differentiation by releasing suppression of the MEK-ERK pathway and increasing the expression of C/EBPβ. This effect is often synergistic when combined with all-trans retinoic acid (ATRA). In glioblastoma, WNK1 signaling is linked to Connexin 43 (Cx43) and supports the survival and self-renewal of cancer stem cells (CSCs). Pharmacologic inhibition of WNK1 has demonstrated anti-leukemic activity and toxicity against glioblastoma CSCs in preclinical models.

Other names

WNK lysine-deficient protein kinase 1 inhibitorWith-no-Lysine kinase 1 inhibitor