Bay 11-7085 is an inhibitor of NF-κB activation and phosphorylation of IκBα with an IC50 value of 10μM for IκBα[1]. Bay 11-7085 inactivates protein tyrosine phosphatases (PTPs) by forming a covalent adduct with the active-site cysteine and inhibits the signal-induced nuclear translocation of NFκB through inhibiting IKK activity and the phosphorylation of IκB in response to the signal [2]. Bay 11-7085 has been widely used to inhibit and eradicate the formation of biofilms by various pathogens, and to prevent the growth of various pathogenic microorganisms[3].
In vitro, Bay 11-7085 treatment for 24 hours significantly inhibited the viability of Nalm6 cells and Raji cells, with IC50 values of 0.5μM and 3.1μM, respectively[4]. Treatment with 10μM Bay 11-7085 for 2 hours induces an increase in LC3B-II in human synovial fibroblasts, phosphorylation of the glucocorticoid receptor (GR) at serine 211, and promotes autophagy of the cells[5]. Treatment with 4μM Bay 11-7085 for 24 hours promoted apoptosis in L1210 cells, accompanied by an increase in caspase-3 activity[6].
In vivo, Bay 11-7085 treatment via intraperitoneal injection (5mg/kg) every three days for a total of 9 days significantly reduced the tumor burden in the Su.86 xenograft mouse model [7]. Weekly intraperitoneal injection of Bay 11-7085 (5mg/kg) twice for 28 days significantly reduced the tumor volume and liver metastasis in the HT-29 xenograft mouse model[8].
References:
[1] Pierce J W, Schoenleber R, Jesmok G, et al. Novel inhibitors of cytokine-induced IκBα phosphorylation and endothelial cell adhesion molecule expression show anti-inflammatory effects in vivo[J]. Journal of Biological Chemistry, 1997, 272(34): 21096-21103.
[2] Krishnan N, Bencze G, Cohen P, et al. The anti‐inflammatory compound BAY‐11‐7082 is a potent inhibitor of protein tyrosine phosphatases[J]. The FEBS journal, 2013, 280(12): 2830-2841.
[3] Escobar I E, Possamai Rossatto F C, Kim S M, et al. Repurposing kinase Inhibitor Bay 11-7085 to combat Staphylococcus aureus and Candida albicans biofilms[J]. Frontiers in Pharmacology, 2021, 12: 675300.
[4] Berger N, Bassat H B, Klein B Y, et al. Cytotoxicity of NF-κB inhibitors Bay 11-7085 and caffeic acid phenethyl ester to Ramos and other human B-lymphoma cell lines[J]. Experimental hematology, 2007, 35(10): 1495-1509.
[5] Relic B, Charlier E, Deroyer C, et al. BAY 11-7085 induces glucocorticoid receptor activation and autophagy that collaborate with apoptosis to induce human synovial fibroblast cell death[J]. Oncotarget, 2016, 7(17): 23370.
[6] Cory A H, Cory J G. Induction of apoptosis in p53-deficient L1210 cells by an I-κ-B-α-inhibitor (Bay 11-7085) via a NF-κ-B-independent mechanism[J]. Advances in enzyme regulation, 2005, 45(1): 85-93.
[7] Shen Y, Herde R, Doxey B W, et al. Pharmacologic downregulation of c‐FLIPL restores juxtacrine death receptor‐mediated apoptosis in cancer cells in a peritoneal carcinomatosis model[J]. International journal of cancer, 2012, 130(7): 1494-1503.
[8] Scaife C L, Kuang J, Wills J C, et al. Nuclear factor κB inhibitors induce adhesion-dependent colon cancer apoptosis: implications for metastasis[J]. Cancer research, 2002, 62(23): 6870-6878.
Bay 11-7085是一种NF-κB活化和IκBα磷酸化的抑制剂，对IκBα的IC50值为10μM [1]。Bay 11-7085通过与活性位点半胱氨酸形成共价加合物来灭活蛋白酪氨酸磷酸酶(PTPs)，并通过抑制IKK活性以及响应信号时IκB的磷酸化来抑制信号诱导的NFκB核转位[2]。Bay 11-7085已被广泛用于抑制和根除多种病原体形成的生物膜，并预防多种病原微生物的生长[3]。
在体外，Bay 11-7085处理24小时显著抑制了Nalm6细胞和Raji细胞的活力，IC50值分别为0.5μM和3.1μM[4]。10μM的Bay 11-7085处理人滑膜成纤维细胞2小时，可诱导LC3B-II增加、糖皮质激素受体(GR)在丝氨酸211位点磷酸化，并促进细胞自噬[5]。4μM的Bay 11-7085处理L1210细胞24小时，促进了细胞凋亡，同时伴随caspase-3活性升高[6]。
在体内，每隔三天腹腔注射5mg/kg剂量的Bay 11-7085，共9天，显著降低了Su.86异种移植小鼠模型中的肿瘤负荷[7]。每周腹腔注射5mg/kg的Bay 11-7085两次，持续28天，显著降低了HT-29异种移植小鼠模型中的肿瘤体积和肝转移[8]。