生物活性

• 描述HSC70 and HSP70 are the two major cytosolic isoforms of the HSP70 family. Between this two proteins, HSP70 is present at relatively low levels in normal cells but can be elevated in expression to protect cells from apoptosis in response to various stressful stimuli such as anticancer agents, especially the HSP90 inhibitors, making it become an important target for anticancer therapy due to its antiapoptotic and oncogenic functions. Apoptozole is a dual HSC70 and HSP70 inhibitor with Kd values of 0.21μM and 0.14μM (measured by SPR spectroscopy), which can potently induced apoptosis in P19 and A549 cells up to 90% at concentration of 1μM for 12h^[1]. This strong potency of Apoptozole to apoptosis induction may due to its effect on disrupting the interaction of HSP70 with APAF-1, which can be bound with by HSP70 and halt the progression of the caspase-dependent apoptotic pathway. Intraperitoneal injection with Apoptozole at dose of 4mg/kg/day every other day for 2 weeks could significantly reduce tumor growth of the A549, RKO, and HeLa xenografts up to 61%, 65% and 68%. Combined treatment of Apoptozole with Doxorubicin can enhance the potency of the agent alone^[2].
• 作用机制Apoptozole can bind to the ATPase domain of HSP70 and block its ATPase activity.^[1]

• 动物研究
  剂量	Mice[2] (i.p.): 4 mg/kg, 10 mg/kg
  给药途径	i.p.
  动物药代数据	Animal Mice[2] Dose 10 mg/kg Administration i.p. T1/2 8.04 h Tmax 1 h Cmax 2159.13 ± 278.25 mg/l AUC0→∞ 10951.73 mg·h/l MRT0→∞ 7.9 h AUC0→t 9969.93 mg·h/l