Aminoxyrone is a novel peptidometic C-terminal HSP90 inhibitor by targeting HSP90 dimerization via the C-terminal domain (CTD) with Kd of 27.4 uM; destabilizes BCR-ABL1 without inducing HSR in vitro and in vivo, additionally reduces pAKT-S473, pS6 expression and expression of client proteins associated with HSP90 chaperone activity, involving t-AKT, t-STAT5a, t-CRKL, cMYC, and BCL2; triggers the degradation of HSP90 client proteins without elevating the expression of HSPs (HSP70, HSP40 & HSP27); significantly inhibits cell growth and induces apoptosis of human leukemic stem cells (LSCs) with average EC50 of 20.94 uM, Aminoxyrone is effective in imatinib resistant CML and lacks heat shock response.
