KRIBB11 is a potent heat shock factor 1 (HSF1) inhibitor, with an IC50 value of 1.2µM[1]. KRIBB11 promotes the proteasomal degradation of Mcl-1 by mediating the ubiquitination increase through the E3 ubiquitin ligase Mule, thereby exerting an apoptotic effect[2]. KRIBB11 has been widely used to promote microglial process elongation and suppress neuroinflammation[3].
In vitro, KRIBB11 treatment for 48 hours significantly inhibited the viability of MCF-7, BT-474, and BT-20 cells, with IC50 values of 3µM, 25µM, and 16µM, respectively [4]. Treatment with 12.5µM KRIBB11 for 24h induced DNA damage, upregulated p53 and p21, and reduced the expression of cyclin D2/E, CDK2/4, c-Myc, MDM2, and β-catenin in human T-cell leukemia virus type 1 (HTLV-1)-infected T cells[5]. 5µM of KRIBB11 incubation for 48 hours significantly promoted apoptosis of A172 cells, accompanied by accumulation of p53 and decrease in p27 levels[6].
In vivo, a single intraperitoneal injection of KRIBB11 (5mg/kg) 1 hour before lipopolysaccharide (LPS) injection suppressed the expression of iNOS protein and mRNA in the brain tissue of endotoxemic mice[7]. Intraperitoneal injection of KRIBB11 at a dose of 50mg/kg/day for 8 consecutive days, combined with 4 sessions of Modulated electro-hyperthermia (mEHT), inhibited tumor growth in the 4T1 xenograft mouse model[8]. Continuous intraperitoneal injection of KRIBB11 (50mg/kg/day) for 30 consecutive days delayed the occurrence of pancreatic cancer in LSL-KrasG12D/+; Pdx1-Cre mice and inhibited the formation of pancreatic cancer precancerous lesions induced by pancreatitis[9].
References:[1]Yoon Y J, Kim J A, Shin K D, et al. KRIBB11 inhibits HSP70 synthesis through inhibition of heat shock factor 1 function by impairing the recruitment of positive transcription elongation factor b to the hsp70 promoter[J]. Journal of Biological Chemistry, 2011, 286(3): 1737-1747.
[2] Kang M J, Yun H H, Lee J H. KRIBB11 accelerates Mcl-1 degradation through an HSF1-independent, Mule-dependent pathway in A549 non-small cell lung cancer cells[J]. Biochemical and biophysical research communications, 2017, 492(3): 304-309.
[3] Su J, Dou Z, Hong H, et al. KRIBB11: A promising drug that promotes microglial process elongation and suppresses neuroinflammation[J]. Frontiers in Pharmacology, 2022, 13: 857081.
[4] Carpenter R L, Sirkisoon S, Zhu D, et al. Combined inhibition of AKT and HSF1 suppresses breast cancer stem cells and tumor growth[J]. Oncotarget, 2017, 8(43): 73947.
[5] Ishikawa C, Mori N. Heat shock factor 1 is a promising therapeutic target against adult T-cell leukemia[J]. Medical Oncology, 2023, 40(6): 172.
[6] Yoo K, Yun H H, Jung S Y, et al. KRIBB11 Exerts Anticancer Effects on A172 Glioblastoma Cells via the Cdh1/SKP2/p27 and HSF1/p53/p21 Pathways[J]. Cancer Genomics-Proteomics, 2025, 22(3): 467-477.
[7] Huang C, Lu X, Tong L, et al. Requirement for endogenous heat shock factor 1 in inducible nitric oxide synthase induction in murine microglia[J]. Journal of Neuroinflammation, 2015, 12(1): 189.
[8] Viana P H L, Schvarcz C A, Danics L O, et al. Heat shock factor 1 inhibition enhances the effects of modulated electro hyperthermia in a triple negative breast cancer mouse model[J]. Scientific Reports, 2024, 14(1): 8241.
[9] Qian W, Chen K, Qin T, et al. The EGFR-HSF1 axis accelerates the tumorigenesis of pancreatic cancer[J]. Journal of Experimental & Clinical Cancer Research, 2021, 40(1): 25.