| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 100mg | |||
| Other Sizes |
| Targets |
Cantrixil's mechanism of action involves the induction of apoptosis through the c-Jun N-terminal kinase (JNK) pathway. It increases phosphorylated c-Jun levels, resulting in caspase-mediated apoptosis in ovarian cancer cells. It has potent pan-anticancer activity against a broad range of cancer phenotypes. Its ability to target cancer stem cells makes it a promising agent for preventing recurrence.
|
|---|---|
| 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].
In vitro, Cantrixil has potent pan-anticancer activity against a broad range of cancer phenotypes. It increases phosphorylated c-Jun levels, leading to caspase-mediated apoptosis in ovarian cancer cells. It is a potent and selective SMETI inhibitor. Its activity is characterized by its ability to induce apoptosis in cancer cells, including those that are chemotherapy-resistant. |
| 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].
In vivo, Cantrixil has been shown to prevent recurrence in ovarian cancer models. Its ability to target cancer stem cells suggests it could be effective in preventing tumor relapse after initial treatment. Its potent antitumor activity has been demonstrated in preclinical models, supporting its development as a therapeutic agent for ovarian and potentially other cancers. |
| Enzyme Assay |
The in vitro activity of Cantrixil is assessed using cell viability and apoptosis assays. In a typical protocol, cancer cells (e.g., ovarian cancer cell lines) are seeded in multi-well plates and treated with increasing concentrations of Cantrixil for 48-72 hours. Cell viability is measured using an MTT or CellTiter-Glo assay. Apoptosis is quantified by measuring caspase activity or by staining with Annexin V and propidium iodide.
|
| 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. Cellular assays for Cantrixil involve studying its effects on the JNK signaling pathway. In a typical protocol, cells are treated with Cantrixil, and the levels of phosphorylated c-Jun are measured by Western blot. The activation of caspases is also assessed to confirm the induction of apoptosis. These assays confirm the compound's mechanism of action. |
| 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. The in vivo efficacy of Cantrixil has been evaluated in xenograft mouse models of ovarian cancer. In these studies, human ovarian tumor cells are implanted subcutaneously or orthotopically into immunodeficient mice. When tumors reach a certain size, the animals are treated with Cantrixil. Tumor growth is monitored, and the compound's ability to inhibit tumor growth and prevent recurrence is assessed. |
| ADME/Pharmacokinetics |
Cantrixil has a molecular weight of 408.44 and a molecular formula of C₂₄H₂₄O₆. It is a third-generation benzopyran-based compound. It is typically supplied as a powder for research use. As a research compound, detailed pharmacokinetic data are not typically reported in the public domain, but its properties are well-suited for use in preclinical models of cancer.
|
| Toxicity/Toxicokinetics |
Cantrixil is an investigational anticancer agent, and its toxicity profile is being evaluated in preclinical studies. As an inducer of apoptosis, it is expected to have effects on rapidly dividing cells, including normal tissues. Its safety and tolerability would be carefully assessed in toxicology studies to determine its therapeutic index.
|
| 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 third-generation hyperbenzopyran (SBP) compound encapsulated in cyclodextrin and possesses potential antitumor activity. Intraperitoneal injection of Cantrixil enhances the activation and expression of c-Jun, downregulates phosphorylated extracellular signal-regulated kinase (p-ERK), and induces the activation of caspase-3, -7, and -9, thereby inducing tumor cell apoptosis. c-Jun is a component of the activator protein-1 (AP-1) transcription factor, involved in various cellular processes, including cell cycle progression, differentiation, cell transformation, and apoptosis.
Cantrixil (TRX-E-002-1) is a third-generation benzopyran-based investigational anticancer agent designed to target chemotherapy-resistant cancer stem cells. It induces c-Jun-dependent apoptosis and has potent pan-anticancer activity. It is being investigated for the treatment of ovarian cancer and other malignancies, but it is not an approved drug. |
| 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)
|
| 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
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *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). View More
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)] 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). View More
Oral Formulation 3: Dissolved in PEG400 (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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
