Cantrixil

• CAT Number: I024009
• CAS Number: 2135511-22-5
• Molecular Formula: C24H24O6
• Molecular Weight: 408.44
• Purity: ≥95%
• Synonyms: (3R,4S)-3-(4-hydroxy-3,5-dimethoxyphenyl)-4-(4-hydroxyphenyl)-8-methyl-3,4-dihydro-2H-chromen-7-ol
• InChI: InChI=1S/C24H24O6/c1-13-19(26)9-8-17-22(14-4-6-16(25)7-5-14)18(12-30-24(13)17)15-10-20(28-2)23(27)21(11-15)29-3/h4-11,18,22,25-27H,12H2,1-3H3/t18-,22-/m0/s1
• InChIKey: JFVVPUGGRUGRBJ-AVRDEDQJSA-N
• SMILES: CC1=C(C=CC2=C1OCC(C2C3=CC=C(C=C3)O)C4=CC(=C(C(=C4)OC)O)OC)O

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].
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].
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 T1/2 of 2.5 hours, a Cmax of 8355 ng/mL and an AUC0-∞ of 40600 ng•h/mL[1].

Reference

[1]. Muhammad Wasif Saif, et al. Pharmacology and toxicology of the novel investigational agent Cantrixil (TRX-E-002-1). Cancer Chemother Pharmacol. 2017 Feb;79(2):303-314.
 [Content Brief]

[2]. Ayesha B Alvero, et al. TRX-E-002-1 Induces c-Jun-Dependent Apoptosis in Ovarian Cancer Stem Cells and Prevents Recurrence In Vivo. Mol Cancer Ther. 2016 Jun;15(6):1279-90.
 [Content Brief]