RX-3117 (TV-1360; RX3117; fluorocyclopentenylcytosine), a cytidine analog, is an orally bioavailable and potent DNA synthesis inhibitor with potential anticanceractivity. It is possible that RX-3117 will be utilized to treat tumors that are resistant to gemcitabine.
Physicochemical Properties
| Molecular Formula | C10H12FN3O4 |
| Molecular Weight | 257.22 |
| Exact Mass | 257.081 |
| Elemental Analysis | C, 46.69; H, 4.70; F, 7.39; N, 16.34; O, 24.88 |
| CAS # | 865838-26-2 |
| Related CAS # | 865838-26-2 |
| PubChem CID | 11242315 |
| Appearance | White solid powder |
| Density | 1.8±0.1 g/cm3 |
| Boiling Point | 516.3±60.0 °C at 760 mmHg |
| Flash Point | 266.1±32.9 °C |
| Vapour Pressure | 0.0±3.0 mmHg at 25°C |
| Index of Refraction | 1.721 |
| LogP | -0.72 |
| Hydrogen Bond Donor Count | 4 |
| Hydrogen Bond Acceptor Count | 5 |
| Rotatable Bond Count | 2 |
| Heavy Atom Count | 18 |
| Complexity | 474 |
| Defined Atom Stereocenter Count | 3 |
| SMILES | FC1=C(CO)[C@@H](O)[C@@H](O)[C@@H]1N1C=CC(N)=NC1=O |
| InChi Key | QLLGKCJUPWYJON-HLTSFMKQSA-N |
| InChi Code | InChI=1S/C10H12FN3O4/c11-6-4(3-15)8(16)9(17)7(6)14-2-1-5(12)13-10(14)18/h1-2,7-9,15-17H,3H2,(H2,12,13,18)/t7-,8-,9+/m1/s1 |
| Chemical Name | 4-amino-1-[(1S,4R,5S)-2-fluoro-4,5-dihydroxy-3-(hydroxymethyl)cyclopent-2-en-1-yl]pyrimidin-2-one |
| Synonyms | RX3117; TV1360; RX3117; TV1360; RX 3117; TV 1360; fluorocyclopentenylcytosine |
| 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 | A549 and SW1573 cells demonstrate anti-proliferative activity in response to RX-3117 (11.7, 21 μM; 48 hours) [1]. Urinary cytochrome pump 2 (RX-3117; 1–25 μM; 72 h) inhibits the growth of RX-3117 in HCT-116, MDA-MB-231, PANC-1, Caki-1, MCF7, A549, MKN45, and U251 cells. The corresponding values are 0.39, 0.18, 0.62 and 0.84, 0.34, 0.34, 0.50, 0.83 μM, respectively [2]. In S phase and intercellular space, RX-3117 (5, 10 μM; 4 days) causes cell cycle inference [2]. In MDA-MB-231, RX-3117 (1–5 μM; 24 hours) decreases DNMT1 cell mass in a dose-dependent manner [3]. |
| ln Vivo | In mice that were left naked, RX-3117 (2, 10 mg/kg; intraperitoneal injection; three times a week for five weeks) demonstrated anti-tumor activity [3]. |
| Cell Assay |
Cell Viability Assay[1] Cell Types: A549, SW1573 cells Tested Concentrations: 11.7 . , 21 µM Incubation Duration: 48 hrs (hours) Experimental Results: Displayed anti-proliferative activity in A549 (63.7% cell growth), SW1573 cells (59% cell growth). Apoptosis analysis [2] Cell Types: A549, SW1573 NSCLC cell Tested Concentrations: 5 µM for A549 cells, 10 µM for SW1573 cells Incubation Duration: 4 days Experimental Results: Induced cell cycle arrest in S phase and apoptosis. |
| Animal Protocol |
Animal/Disease Models: Nude mice (human colon cancer HCT116 xenograft model) [3] Doses: 2, 10 mg/kg Route of Administration: IP; 3 times a week for five weeks Experimental Results: Doses of 2 and 10 mg/kg It has a significant inhibitory effect on tumor growth. |
| References |
[1]. The Cytidine Analog Fluorocyclopentenylcytosine (RX-3117) Is Activated by Uridine-Cytidine Kinase 2. PLoS One. 2016 Sep 9;11(9):e0162901. [2]. RX-3117 (fluorocyclopentenyl cytosine): a novel specific antimetabolite for selective cancer treatment. Expert Opin Investig Drugs. 2019 Apr;28(4):311-322. [3]. DNA methyltransferase inhibitors in cancer: a chemical and therapeutic patent overview and selected clinical studies. Expert Opin Ther Pat. 2012 Dec;22(12):1427-42. |
| Additional Infomation |
Roducitabine is a triol that is (1S,2R)-4-fluoro-3-(hydroxymethyl)cyclopent-3-ene-1,2-diol which is substituted by a 4-amino-2-oxopyrimidin-1(2H)-yl group at position 5. It is a cytidine analog which exhibits anticancer activity in several cancers, including gemcitabine-resistant tumours. It has a role as an antimetabolite, an antineoplastic agent, a prodrug, a DNA synthesis inhibitor and an apoptosis inducer. It is an organofluorine compound, a primary allylic alcohol and a triol. Fluorocyclopentenylcytosine is under investigation in clinical trial NCT03189914 (RX-3117 in Combination With Abraxane® in Subjects With Metastatic Pancreatic Cancer). Roducitabine is an orally available small molecule and nucleoside antimetabolite with potential antineoplastic activity. Upon administration, roducitabine is taken up by cells through a carrier-mediated transporter, phosphorylated by uridine cytidine kinase (UCK) and then further phosphorylated to its diphosphate (RX-DP) and triphosphate forms (RX-TP). The triphosphate form is incorporated into RNA and inhibits RNA synthesis. The diphosphate RX-DP is reduced by ribonucleotide reductase (RR) to dRX-DP; its triphosphate form (dRX-TP) is incorporated into DNA. In addition, roducitabine also inhibits DNA methyltransferase 1 (DNMT1). This eventually leads to cell cycle arrest and the induction of apoptosis. UCK is the rate-limiting enzyme in the pyrimidine-nucleotide salvage pathway. |
Solubility Data
| Solubility (In Vitro) | DMSO: ≥ 50 mg/mL (~194.4 mM) |
| 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 | 3.8877 mL | 19.4386 mL | 38.8772 mL | |
| 5 mM | 0.7775 mL | 3.8877 mL | 7.7754 mL | |
| 10 mM | 0.3888 mL | 1.9439 mL | 3.8877 mL |