| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
Ethynylcytidine targets RNA polymerase, the enzyme responsible for RNA synthesis. After intracellular phosphorylation to its active triphosphate form, Ethynylcytidine inhibits RNA polymerase activity, blocking the synthesis of RNA. This leads to the inhibition of protein synthesis and induction of apoptosis in cancer cells. The compound shows selectivity for cancer cells over normal cells.
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| ln Vitro |
At 4, 24, and 72 hours of exposure, the cytidine ethinyl IC50 values in five human cancers were 0.114 to 1.032 μM, 0.015 to 0.067 μM, and 0.008 to 0.058 μM, respectively. These findings suggest that cytidine ethinyl's cytotoxicity tends to rise with longer exposure times. At the 24-hour exposure time, cytidine ethinyl seemed to demonstrate adequately strong cytotoxicity against all five human cancers, and the difference in IC50 values between the 24- and 72-hour exposure times was not significant. Cytidine ethinyl exhibits strong cytotoxicity even after four hours of treatment, as evidenced by IC50 values in four out of five human malignancies at submicromolar doses [1].
In vitro, Ethynylcytidine acts as a potent inhibitor of RNA synthesis. It is phosphorylated intracellularly to its active triphosphate form, which inhibits RNA polymerase. The compound demonstrates antiproliferative activity against various cancer cell lines. Ethynylcytidine induces apoptosis in cancer cells by inhibiting RNA and protein synthesis. Specific IC50 values for antiproliferative activity are available from cell-based assays. |
| ln Vivo |
Tumor growth inhibition ratio (IR) on day 15 of approximately OCUM-2MD3 and LX-1 xenografts showed tumor regression and a strong antitumor effect at the lowest toxic dose of cytidine ethinyl. 90% or higher. TAS-106 in each of the three management schemes. Specifically, once-weekly treatment with 6 mg/kg cytidine ethinyl resulted in a 98% internal rate of decay (IR) for LX-1 tumors. While once-weekly cytidine ethinyl treatment has an IR of less than 60% and a very weak anti-tumor effect, treatment with cytidine ethinyl three or five times a week has an effective anti-tumor effect with an IR of about 85%[1].
In vivo, Ethynylcytidine has been investigated as an anticancer agent in preclinical and clinical studies. The compound has shown antitumor efficacy in various xenograft models. Ethynylcytidine's mechanism of action, involving inhibition of RNA synthesis, makes it effective against rapidly proliferating tumor cells. The compound has been evaluated in clinical trials for the treatment of solid tumors. |
| Enzyme Assay |
The in vitro enzyme activity assay for Ethynylcytidine involves measuring its inhibitory effect on RNA polymerase activity after phosphorylation to its active triphosphate form. RNA polymerase is incubated with varying concentrations of Ethynylcytidine triphosphate and a DNA template with radiolabeled nucleotides. RNA synthesis is measured by scintillation counting. The IC50 for RNA polymerase inhibition is determined from dose-response curves.
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| Cell Assay |
In vitro cellular assays for Ethynylcytidine involve treating cancer cell lines with varying concentrations of the compound. The compound is phosphorylated intracellularly to its active triphosphate form. RNA synthesis is assessed by measuring incorporation of radiolabeled uridine. Cell proliferation is assessed using MTT or colony formation assays. Apoptosis is detected by flow cytometry using Annexin V/PI staining.
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| Animal Protocol |
In vivo animal experiments for Ethynylcytidine typically use mouse xenograft models of human cancers. Tumor-bearing mice are administered Ethynylcytidine via intravenous or oral routes at various doses. Tumor volume is measured regularly. RNA synthesis inhibition and apoptosis are assessed in tumor tissues. The compound's antitumor efficacy is evaluated by comparing tumor growth delay in treated versus control groups.
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| ADME/Pharmacokinetics |
Ethynylcytidine is a nucleoside analog with a molecular weight of 267.24 (C11H13N3O5). It is administered intravenously and is phosphorylated intracellularly to its active triphosphate form. The compound is cleared primarily via renal excretion. Specific PK parameters including half-life, volume of distribution, and clearance are available from clinical pharmacology studies.
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| Toxicity/Toxicokinetics |
Ethynylcytidine has been evaluated in clinical trials for the treatment of solid tumors. As an RNA synthesis inhibitor, potential adverse effects may include myelosuppression, gastrointestinal toxicity, and hepatotoxicity. The compound's selectivity for cancer cells may reduce some toxicities. Complete toxicology data including acute, repeated-dose, and genotoxicity studies are available from the compound's clinical development program.
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| References | |
| Additional Infomation |
3'-C-ethynylcytidine is a pyrimidine nucleoside. TAS-106 is a novel nucleoside antimetabolite. In nude mouse models carrying human tumors, TAS-106 has shown potent antitumor activity without serious toxicity. 3'-C-ethynylcytidine is a synthetic cytidine nucleoside containing a covalently linked ethynyl group, possessing potential antitumor and radiosensitizing activities. In tumor cells, 3'-C-ethynylcytidine is metabolized to etynylcytidine triphosphate (ECTP), which competitively inhibits RNA synthesis by inhibiting RNA polymerases I, II, and III; subsequently, RNase L is activated, leading to apoptosis. RNase L is a potent antiviral and antiproliferative endoribonuclease that cleaves single-stranded RNA, leading to 28S rRNA fragmentation and activation of Janus kinase (JAK), a mitochondrial-dependent apoptosis signaling molecule. Drug Indications Investigated for the treatment of solid tumors and cancer/tumor (not specified). Mechanism of Action 3'-C-ethynylcytidine is metabolized in tumor cells to ethynylcytidine triphosphate (ECTP). ECTP inhibits RNA synthesis by competitively inhibiting RNA polymerases I, II, and III; subsequently, RNase L is activated, leading to apoptosis. RNase L is a potent antiviral and antiproliferative endoribonuclease that cleaves single-stranded RNA, resulting in 28S rRNA fragmentation and activation of Janus kinase (JAK), a mitochondrial-dependent apoptosis signaling molecule.
Ethynylcytidine (CAS#: 180300-43-0) is a nucleoside analog that acts as a potent inhibitor of RNA synthesis, also known as TAS-106. It is phosphorylated intracellularly to its active triphosphate form, which inhibits RNA polymerase, leading to inhibition of RNA synthesis and induction of apoptosis. Ethynylcytidine has been investigated as an anticancer agent in preclinical and clinical studies. The compound is not approved for clinical use. |
| Molecular Formula |
C11H13N3O5
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| Molecular Weight |
267.23802
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| Exact Mass |
267.086
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| Elemental Analysis |
C, 49.44; H, 4.90; N, 15.72; O, 29.93
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| CAS # |
180300-43-0
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| PubChem CID |
176885
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| Appearance |
White to yellow solid powder
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| Density |
1.61g/cm3
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| Boiling Point |
536.4ºC at 760 mmHg
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| Flash Point |
278.2ºC
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| Vapour Pressure |
9.56E-14mmHg at 25°C
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| Index of Refraction |
1.677
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| LogP |
-2.7
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
19
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| Complexity |
508
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| Defined Atom Stereocenter Count |
4
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| SMILES |
C#C[C@]1([C@H](O[C@H]([C@@H]1O)N2C=CC(=NC2=O)N)CO)O
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| InChi Key |
JFIWEPHGRUDAJN-DYUFWOLASA-N
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| InChi Code |
InChI=1S/C11H13N3O5/c1-2-11(18)6(5-15)19-9(8(11)16)14-4-3-7(12)13-10(14)17/h1,3-4,6,8-9,15-16,18H,5H2,(H2,12,13,17)/t6-,8+,9-,11-/m1/s1
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| Chemical Name |
4-amino-1-[(2R,3R,4S,5R)-4-ethynyl-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one
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| Synonyms |
SB596168; 3 Ethynylcytidine; ECyd; TAS106; NSC 722662; TAS 106; 3CEthynylcytidine; AIDS241582; AIDS241582; 3'-ethynylcytidine; ECyd; TAS-106; NSC722662; NSC-722662
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~250 mg/mL (~935.49 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (7.78 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (7.78 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (7.78 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.7420 mL | 18.7098 mL | 37.4195 mL | |
| 5 mM | 0.7484 mL | 3.7420 mL | 7.4839 mL | |
| 10 mM | 0.3742 mL | 1.8710 mL | 3.7420 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.
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