Hsp90 inhibitor with anti-cancer efficacy in vitro and in vivo.
YZ129 is an ATP site-targeting Hsp90 inhibitor (IC50 = 29.5 nM against 2.5 nM geldanamycin-FITC for binding human HSP90α) that prevents thapsigargin (1 μM)-induced NFAT nuclear translocation in HeLa cells (IC50 = 820 nM) by blocking HSP90 client calcineurin-mediated NFAT dephosphorylation. YZ129 (5 μM; 24-48 hr) suppresses U87 glioblastoma (GBM) cell migration and proliferation as a result of G2/M arrest and apoptosis induction. Daily intraperitoneal administration is efficacious against U87 xenografts (s.c.; bilateral posterior limbs)-derived tumor growth in mice in vivo.
Cell chemical biology, 26(3), 352-365 (2019-01-15)
Glioblastoma (GBM) is among the most common and malignant types of primary brain tumors in adults, with a dismal prognosis. Although alkylating agents such as temozolomide are widely applied as the first-line treatment for GBM, they often cause chemoresistance and
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