Cantrixil

Cantrixil (TRX-E-002-1), an active enantiomer of TRX-E-002, is a second-generation super-benzopyran (SBP) compound. Cantrixil increases phosphorylated c-Jun levels resulting in caspase-mediated apoptosis in ovarian cancer cells. Cantrixil has potent pan anti-cancer activity against a broad range of cancer phenotypes^[1][2]. In Vitro: TRX-E-002-1 shows broad cytotoxic activity against ovarian, prostate and lung cancer cells, with IC₅₀ values of ≤0.1 μM (SK-OV-3, JAM, OVCAR-3 cells: IC₅₀=0.023-0.065 μM; DU145, PC3; C4-2B cells: IC₅₀=0.014-0.096 μM; A549 cells: IC₅₀=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. IC₅₀ values ranges from 1.5 to 75 μM (612-30,600 ng/mL)^[1].
In Vivo: 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].