生物活性

• 靶点	HSP IC50:1.2μM

• 描述HSF1 (heat shock factor 1) is the master switch for heat shock protein (HSP) expression in eukaryotes. KRIBB11 is an HSF1 inhibitor with IC₅₀ value of 1.2 μM for abolishing the heat shock-induced luciferase activity. Exposure to KRIBB11 at concentration < 50 μM 30min prior to heat shock at 43℃ for 1 h and further incubation at 37℃ for 1 h could dose-dependently inhibit the heat shock-induced transcription of hsp70, hsp47, and hsp27 in HCT116 cells. And this concentration-dependent inhibition of hsp70 and hsp27 can be also observed on protein level at concentration < 10 μM. Treatment with KRIBB11 for 48h at concentration ranging in 1-30 μM could inhibit proliferation of HCT116 cells by arresting the cell cycle at the G2/M phase, and apoptosis can be induced in both dose (1-20 μM, for 48 h)- and time (10 μM, 3-48 h)-dependent manner. Intraperitoneal injection with KRIBB11 at 50 mg/kg for 18 days could inhibit tumor growth in HCT-116 cells xenograft mice, with much lower expression of HSP70 observed in tumor tissue^[1].
• 作用机制KRIBB11 can bind to HSF-1 and inhibit heat shock-induced recruitment of p-TEFb to the hsp70 promoter and phosphorylation of RNA pol II CTD Ser-2.^[1]

• 动物研究
  剂量	Mice (i.p.): 5 mg/kg[2], 50 mg/kg[3], 65 mg/kg[4]
  给药途径	i.p.