APX2014

APX2014 is a Ref-1/APE1 inhibitor that inhibits Ref-1-induced transcription factor-DNA binding, thereby reducing the activation level of NF-κB and the expression of downstream pro-angiogenic targets. APX2014 blocks endothelial cell proliferation, lumen formation, migration and choroidal sprouting to exert anti-angiogenic activity. APX2014 activates the ISR pathway, promotes the death of pancreatic cancer cells and cancer-associated fibroblasts, and induces apoptosis in the absence of PRDX1. APX2014 inhibits the growth of pancreatic cancer spheroids, reduces the volume/weight of xenograft tumors, and decreases Ki-67 levels by targeting PRDX1. APX2014 can be used in research related to macular degeneration, retinopathy and pancreatic ductal adenocarcinoma^[1][2][3]. In Vitro:APX2014 (0.3-4 μM; 30 min) potently inhibits Ref-1-induced AP-1 DNA binding in cell-free EMSA assays, with an IC₅₀ of 0.2 μM^[1].
APX2014 binds directly to a small surface pocket on purified Ref-1 and targets the redox regulatory function of Ref-1 without affecting its DNA repair activity^[2].
APX2014 (24-48 h) inhibits the proliferation of human retinal microvascular endothelial cells in vitro with a GI₅₀ of 110 nM; it also inhibits the proliferation of rhesus monkey choroidal endothelial cells (Rf/6a) in vitro with a GI₅₀ value of 5.0 μM^[1].
APX2014 (0.5-10 μM; 8-16 h) dose-dependently inhibits the migration of human retinal microvascular endothelial cells (HRECs) and rhesus monkey choroidal endothelial cells (Rf/6a) in vitro scratch assays^[1].
APX2014 (0.03-0.3 μM) dose-dependently inhibits tube formation by human retinal microvascular endothelial cells (HRECs) and rhesus monkey choroidal endothelial cells (Rf/6a) in in vitro Matrigel assays^[1].
APX2014 (0.03-0.3 μM; 17 h) dose-dependently blocks human retinal microvascular endothelial cells (HRECs) from entering the S phase and reduces their proliferative capacity^[1].
APX2014 (0.03-0.3 μM; 17 h) dose-dependently inhibits TNF-α-mediated nuclear translocation of NF-κB p65 and reduces the mRNA expression of pro-angiogenic genes (VEGFA, VCAM1, CCL20) in human retinal microvascular endothelial cells (HRECs)^[1].
APX2014 (0.63‑12.5 μM; 48 h) exhibited enhanced cellular sensitivity upon PRDX1 knockdown in Pa03C, Panc‑1 pancreatic ductal adenocarcinoma (PDAC) cells and CAF19 fibroblasts; knockdown of other peroxiredoxins did not alter cellular sensitivity to this agent^[2].
APX2014 (5-10 μM; 24 h) inhibits the transcriptional activities of HIF-1α and NF-κB in Pa03C pancreatic ductal adenocarcinoma (PDAC) cells, and enhanced inhibition is observed in PRDX1-knockdown or PRDX1-knockout cells^[2].
APX2014 (2.5-10 μM; administered on days 4-12 of spheroid culture) exerts stronger growth inhibitory effects on Pa03C PRDX1KO PDAC spheroids than on Cas9 control spheroids, both in monoculture and CAF co-culture systems; when co-cultured with PRDX1KD CAFs, it also induces significant CAF death at multiple concentrations^[2].
APX2014 (5-10 μM; 24-48 h) induces dose- and time-dependent late apoptosis/necrosis in Pa03C PRDX1KO 1A2 pancreatic ductal adenocarcinoma (PDAC) cells^[2].
APX2014 (5-20 μM; 6 h) activates the integrated stress response (ISR) pathway in Pa03C human pancreatic ductal adenocarcinoma (Pa02C, Panc10.05) cells via dose-dependent induction of p-PERK, p-eIF2α and ATF4^[3].
APX2014 (0.0001-100 μM; 6 h) potently activates the transcriptional activity of ATF4 in HEK293 cells, and its efficacy is superior to that of APX2009 (HY-120069) and APX3330 (HY-19357)^[3]. In Vivo:APX2014 (50 mg/kg; i.t.; once daily; 5 days of treatment followed by 2 days of rest) significantly reduces tumor volume, tumor weight, and tumor cell proliferation, and improves survival in NSG mice bearing PRDX1-knockout pancreatic ductal adenocarcinoma xenografts^[2].