Cantrixil (TRX-E-002-1) is a second-generation super-benzopyran (SBP) compound, derived from TRX-E-002. It elicits an increase in phosphorylated c-Jun levels, leading to caspase-mediated apoptosis in ovarian cancer cells. Cantrixil exhibits potent pan anti-cancer activity against various cancer phenotypes.

TRX-E-002-1 shows broad cytotoxic activity against ovarian, prostate and lung cancer cells, with IC 50 values of ≤0.1 μM (SK-OV-3, JAM, OVCAR-3 cells: IC 50 =0.023-0.065 μM; DU145, PC3; C4-2B cells: IC 50 =0.014-0.096 μM; A549 cells: IC 50 =0.058 μM). Activity in pancreatic and colorectal cancer cells and glioblastoma cells are more variable[1]. Cantrixil (0.2 μM; 2-24 hours) shows high levels of phosphorylated c-Jun (p-c-Jun) and low levels of phosphorylated-ERK (p-ERK)[2]. Cantrixil (2.45 μM; 2-24 hours) induces a significant increase in both caspase-3/7 and caspase-9 activity at 16 and 24 hours[2]. TRX-E-002-1 inhibits multiple cytochrome P450 drug-metabolizing enzymes, including CYP2C9, CYP2C8, CYP2C19, CYP2B6, CYP3A4, CYP2D6, CYP2A6 and CYP1A2. IC 50 values ranges from 1.5 to 75 μM (612-30,600 ng/mL)[1]. Western Blot Analysis[2]Cell Line: Ovarian cancer stem cells (OCSCs) Concentration: 0.2 μM Incubation Time: 2, 4, 8, 16, 24 hours Result: Showed higher levels of phosphorylated c-Jun (p-c-Jun) and lower levels of phosphorylated-ERK (p-ERK). Showed a time-dependent increase in p-c-Jun accompanied by a time-dependent increase in total c-Jun.

TRX-E-002-1 (100 mg/kg/day; IP; for 13-14 days) significantly inhibits tumour growth in disseminated ovarian cancer mouse model[1]. TRX-E-002-1 (100 mg/kg/day; IP; for 4 weeks) inhibits tumour growth and reduces terminal tumour burden by 77% in the recurrent ovarian cancer mouse model[1]. TRX-E-002-1 (100 mg/kg/day; IP; for 18 days) significantly reduces terminal pancreatic tumour burden in a mouse model of pancreatic cancer (human Panc-1 pancreatic tumour cells implanted orthotopically into female NOD-SCID mice)[1]. TRX-E-002-1 (100 mg/kg; IP) has a T 1/2 of 2.5 hours, a C max of 8355 ng/mL and an AUC 0-∞ of 40600 ng?h/mL[1]. Animal Model: Disseminated ovarian cancer mouse model[1]Dosage: 100 mg/kg (dissolved in 20% SBECD) Administration: IP; once daily; for 13-14 days Result: Significantly inhibited tumour growth and reduced excised tumour weight at termination by 50-72%. Animal Model: Male female Sprague-Dawley rats[1]Dosage: 100 mg/kg (Pharmacokinetic Analysis) Administration: IP Result: Had a T 1/2 of 2.5 hours, a C max of 8355 ng/mL and an AUC 0-∞ of 40600 ng?h/mL.