生物活性

• 靶点

  HSP90α IC50:13nM

  HSP90β IC50:21nM

• 描述HSP90 (heat shock protein 90) is a cellular ubiquitous molecular chaperone responsible for promoting the conformational mutation and stabilization of several client oncoproteins, including Met, B-Raf, p53, Akt, and Kit, function of which is required by tumor cells to maintain appropriate client protein expression necessary for proliferation and survival. Luminespib is a potent HSP90 inhibitor with IC50 value of 21nM (measured by a fluorescence polarization (FP) competitive binding assay). Treatment with luminespib dose-dependently led to decreased of protein level of its client protein Her2 and Raf-1 and increased HSP72 at 16nM or 32nM for 24h and anti-proliferation with GI50 of 16nM in HCT116 cells. In vivo study showed that luminespib had a comparatively high tumor concentration with tumor/plasma ratio of 2.3 at a dose of 4mg/kg. Intraperitoneal injection of luminespib at dose of 50mg/kg, q.d., for 12 days achieved almost 50% tumor growth inhibition in HCT116 human colon carcinoma xenografts, with decreased Raf-1, Her2 and increased HSP72 at 6h after the final dose, which showed the pharmacodynamic of it^[1].
• 作用机制Luminespib can bound to the ATP binding site of human Hsp90-alpha.^[1]

• 动物研究
  剂量	Mice: 50 mg/kg[2] (i.p., i.v.)
  给药途径	i.p., i.v.
  动物药代数据	Animal Mice Dose 4 mg/kg Administration i.p. T1/2 9.5 h Tmax 1 h AUClast 1720 h·nmol/l Cmax 385.4 nmol/l