Cantrixil (TRX-E-002-1) is the active enantiomer of TRX-E-002, a second-generation superbenzopyran (SBP) compound. Cantrixil increases phosphorylated c-Jun levels, leading to caspase-mediated apoptosis in ovarian cancer/tumor cells. Cantrixil has potent anti-cancer effect across a broad range of cancer phenotypes.

Physicochemical Properties

Molecular Formula	C24H24O6
Molecular Weight	408.443767547607
Exact Mass	408.157
CAS #	2135511-22-5
PubChem CID	129851403
Appearance	Off-white to light brown solid powder
LogP	4.4
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	4
Heavy Atom Count	30
Complexity	536
Defined Atom Stereocenter Count	2
SMILES	CC1=C(C=CC2=C1OC[C@H]([C@H]2C3=CC=C(C=C3)O)C4=CC(=C(C(=C4)OC)O)OC)O
InChi Key	JFVVPUGGRUGRBJ-AVRDEDQJSA-N
InChi Code	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
Chemical Name	(3R,4S)-3-(4-hydroxy-3,5-dimethoxyphenyl)-4-(4-hydroxyphenyl)-8-methyl-3,4-dihydro-2H-chromen-7-ol
Synonyms	TRXE-002-1; TRX-E-002-1; Cantrixil
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	With an IC50 value of less than 0.1 μM, TRX-E-002-1 exhibits extensive cytotoxic activity against cells related to lung, prostate, and ovarian cancer (SK-OV-3, JAM, and OVCAR-3 cells: IC50=0.023-0.065 μM; DU145, PC3; C4-2B cells: IC50=0.014-0.096 μM; A549 cells: IC50=0.058μM). Greater activity variability is observed in glioblastoma, colorectal, and pancreatic cancer cells [1]. High levels of phosphorylated c-Jun (pc-Jun) and low levels of phospho-ERK (p-ERK) are observed in response to cantrixil (0.2 μM; 2-24 hours) [2]. At 16 and 24 hours, cantrixil (2.45 μM; 2–24 hours) significantly enhances caspase-3/7 and caspase-9 activity [2]. Many cytochrome P450 drug-metabolizing enzymes, including as CYP2C9, CYP2C8, CYP2C19, CYP2B6, CYP3A4, CYP2D6, CYP2A6, and CYP1A2, are inhibited by TRX-E-002-1. The range of IC50 values is 1.5 to 75 μM (612-30,600 ng/mL) [1].
ln Vivo	A mouse model of disseminated ovarian cancer shows that TRX-E-002-1 (100 mg/kg/day; IP; for 13–14 days) effectively reduces tumor growth [1]. TRX-E-002-1 (100 mg/kg/day; intraperitoneal injection; for 4 weeks) decreased the end-stage tumor burden by 77% and prevented the formation of tumors in a mouse model of recurrent ovarian cancer [1]. Human Panc-1 pancreatic tumor cells were orthotopically implanted into female NOD-SCID mice to create a mouse model in which TRX-E-002-1 (100 mg/kg/day; IP; for 18 days) dramatically lowers the incidence of pancreatic cancer. burden of end-stage pancreatic tumors) [1]. AUC0-∞ of 40600 ng·h/mL, a Cmax of 8355 ng/mL, and a T1/2 of 2.5 hours are reported for TRX-E-002-1 (100 mg/kg; IP)[1].
Cell Assay	Western Blot Analysis[2] Cell Types: Ovarian Cancer Stem Cells (OCSC) Tested Concentrations: 0.2 μM Incubation Duration: 2, 4, 8, 16, 24 hrs (hours) Experimental Results: Higher and lower levels of phosphorylated c-Jun (pc-Jun) Phosphorylated ERK (p-ERK) levels. A time-dependent increase in pc-Jun was shown, along with a time-dependent increase in total c-Jun.
Animal Protocol	Animal/Disease Models: disseminated ovarian cancer mouse model [1] Doses: 100 mg/kg (dissolved in 20% SBECD) Route of Administration: IP; one time/day; for 13-14 days Experimental Results: Dramatically inhibited tumor growth and The weight of the resected tumor at termination was diminished by 50-72%. Animal/Disease Models: Male and female SD (SD (Sprague-Dawley)) rats [1] Doses: 100 mg/kg (pharmacokinetic/PK/PK analysis) Route of Administration: IP Experimental Results: T1/2 is 2.5 hrs (hrs (hours)), Cmax is 8355 ng/mL, AUC0-∞ is 40600 ng·h/ml.
References	[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. [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.
Additional Infomation	Cantrixil is a cyclodextrin-encapsulated, third generation super-benzopyran (SBP) compound with potential antineoplastic activity. Upon intraperitoneal (IP) administration, cantrixil enhances the activation and expression of c-Jun, downregulates phosphorylated extracellular signal-regulated kinase (p-ERK) and induces activation of caspase-3, -7 and -9, thereby inducing tumor cell apoptosis. c-Jun, an activator protein-1 (AP-1) transcription factor component, is involved in a wide range of cellular processes including cell cycle progression, differentiation, cell transformation and apoptosis.

Solubility Data

Solubility (In Vitro)

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.4483 mL	12.2417 mL	24.4834 mL
	5 mM	0.4897 mL	2.4483 mL	4.8967 mL
	10 mM	0.2448 mL	1.2242 mL	2.4483 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.