AGX51

AGX51 is a first-in-class pan- Id (inhibitors of DNA-binding/differentiation proteins) antagonist and degrader. AGX51 inhibits the Id1-E47 interaction, leading to ubiquitin-mediated degradation of Ids, cell growth arrest, and reduces viability. AGX51 inhibits the TNBC cell lines with IC 50 s of nearly 25 μM. AGX51 can be used for the research of cancer

In Vitro

AGX51 (0-80 μM; 24 h) decreases ID1 protein levels in 4T1 cells. ?\nAGX51 (40 μM; 0-72 h) decreases ID1 levels protein with a 40 μM concentratio in 4T1 cells. ?\nAGX51 (40 μM; 24 h) influences 4T1 cells , ER+, HER2+, TNBC and three breast cancer PDX cell ines. ?\nAGX51 (0-80 μM; 24-48 h) influences cell cycle of 4T1 cells. ?\nAGX51 (40 μM; 4-24 h) influences phospho-histone H3 levels in 4T1 cells. ?\nAGX51 (40 μM; 24 h) influences ROS levels in 4T1 cells. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot AnalysisCell Line: 4T1 cells Concentration: 0, 5, 10, 20, 40 and 80 μM Incubation Time: 24 hours Result: Decreased ID1 protein levels starting at a concentration of 40 μM in 4T1 cells. Western Blot AnalysisCell Line: 4T1 cells Concentration: 40 μM Incubation Time: 0, 2, 4, 8 , 12, 24, 48 and 72 hours Result: Decreased ID1 protein levels starting at 4 h, while until 24 h ID1 protein completely loss. Cell Viability AssayCell Line: 4T1 cells, HMLE RAS Twist , MDA-MB-157, MDA-MB-436, MDA-MB-231, MDA-MB-453, BT-474, MDA-MB-361, SK-BR-3, MCF-7, T47-D, PDX-BR7, PDX-IBT and PDX-BR11 Concentration: 40 μM Incubation Time: 24 hours Result: Inhibited 4T1, HMLE RAS Twist , MDA-MB-157, MDA-MB-436, SK-BR-3, MCF-7, PDX-BR7, PDX-IBT and PDX-BR11 cell lines with IC 50 s of 26.66, 8.7, 22.28, 30.91, 36.55, 60, 10.89, 11.97 and 18.56 μM, respectively. Cell Cycle AnalysisCell Line: 4T1 cells Concentration: 40 μM Incubation Time: 24 and 48 hours Result: Affected cell cycle of 4T1 cells with a G0/G1 phase accumulation. Cell Viability AssayCell Line: 4T1 cells Concentration: 40 μM Incubation Time: 4 and 24 hours Result: Reduced phospho-histone H3 levels in 4T1 cells. Cell Viability AssayCell Line: 4T1 cells Concentration: 40 μM Incubation Time: 24 hours Result: Increased ROS level of 4T1 cells and indicated ROS production is a main mechanism of cell killing.

In Vivo

AGX51 (50 mg/kg; i.p. twice a day for 4 weeks) inhibits lung metastasis . ?\nAGX51 (15 mg/kg; i.p. twice a day for 3 weeks) exibits anti-tumor activity with autochronous cancer . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Balb/c mice with luciferase-labeled 4T1 cells Dosage: 50 mg/kg Administration: Intraperitoneal injection; 60 mg/kg twice a day; for 4 weeks Result: Inhibited lung metastasis development. Animal Model: A/J mice with AOM colon tumor model Dosage: 15 mg/kg Administration: Intraperitoneal injection; 15 mg/kg twice a day; for 3 weeks Result: Dreased the colon tumors and exhibited anti-tumor activity in AOM colon tumor mice.

IC50& Target:IC50: 26.66 μM (4T1), 8.7 μM (HMLE RAS Twist), 22.28 μM (MDA-MB-157), 30.91 μM (MDA-MB-436), 36.55 μM (SK-BR-3), 60 μM (MCF-7), 10.89 μM (PDX-BR7), 11.97 μM (PDX-IBT) , 18.56 μM (PDX-BR11)