生物活性

• 靶点	HSP90 Kd:1.2μM

• 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. Geldanamycin is the first class of HSP90 inhibitor with a Kd value of 1.2 µM and IC50<2μM for ATPase activity of Hsp90^[1]. Treatment with geldanamycin at concentration of 0.5μM or 1μM for 24h reduced the protein level of AKT, as well as Raf-1 and its downstream p-MEK1/2, but not N-Ras or MEK1/2 in SH-SY5Y cells. Geldanamycin at concentration of 1μM for 48h could induce apoptosis in several neuroblastoma cell lines, including SH-SY5Y, SK-N-SH and LAN-1 cells^[2]. Intraperitoneal administration of geldanamycin (10 mg/kg) ameliorated ICH-induced increase of brain water content significantly, improved the neurological outcome and had a neuroprotective effect after ICH^[3].
• 作用机制Geldanamycin can bind to the N-terminal ATP/ADP-binding domain of Hsp90 and minhibit the inherent ATPase activity of Hsp90.^[1]

• 动物研究
  剂量	Mice: 5 mg/kg - 20 mg/kg[4] (i.p.), 0.1 mg/kg - 1 mg/kg[5] (intraplantar)
  给药途径	i.p., intraplantar
  动物药代数据	Animal Mice[6] Dogs[6] Administration i.v. i.v. MRT 20.7 min 46.6 min Vz 4.11 L/kg Vz/F 3.81 L/kg CL 30.5 ml/min/kg 49.4 ml/min/kg Vss 0.68 L/kg 2.31 L/kg