| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
The primary molecular target of Cytarabine 5'-monophosphate is DNA polymerase alpha. After sequential phosphorylation to the triphosphate form (ara-CTP), it competes with deoxycytidine triphosphate (dCTP) for incorporation into DNA by DNA polymerase. Once incorporated, it acts as a chain terminator, as the arabinose sugar prevents further chain elongation. This blocks DNA synthesis and repair. It also inhibits the replication of nuclear DNA and mitochondrial DNA in Saccharomyces cerevisiae at 15 mM. It induces apoptosis in rapidly dividing cells. It is an anticancer agent.
|
|---|---|
| ln Vitro |
In vitro, Cytarabine 5'-monophosphate inhibits the replication of nuclear DNA and mitochondrial DNA in Saccharomyces cerevisiae at a concentration of 15 mM. In cancer cell lines (e.g., HL-60, K562 leukemia), ara-CMP inhibits cell proliferation with IC50 values in the low micromolar range (0.1-1 uM). It is incorporated into DNA by DNA polymerase alpha, which reduces the rate of DNA synthesis. It is a potent inducer of apoptosis. It is the active metabolite of cytarabine. It is a nucleoside analog. It is used in cancer research.
|
| ln Vivo |
In vivo, Cytarabine 5'-monophosphate (3.5-75.1 mg/kg) can improve the survival rate of leukemia mice (L1210 mice). Cytarabine itself is the drug. Ara-CMP is the active intermediate. When administered systemically, cytarabine is rapidly deaminated in the plasma to the inactive uracil derivative. The success of the drug depends on its conversion to ara-CMP inside the leukemic blast cells. High doses of the drug can achieve therapeutic levels. The compound has activity against lymphoma and acute leukemia. It is a standard chemotherapy agent. It is on the WHO Model List of Essential Medicines.
|
| Enzyme Assay |
Cytarabine 5'-monophosphate is not used as a reagent in non-cellular assays. Instead, the activity is measured using DNA polymerase assays. A standard protocol: Purified DNA polymerase alpha (5 units) is incubated with a template/primer (e.g., poly(dA)-oligo(dT) or activated calf thymus DNA), [3H]-dCTP or [3H]-dTTP, and increasing concentrations of ara-CTP (the triphosphate form). The reaction buffer contains 50 mM Tris-HCl (pH 7.5), 10 mM MgCl2, 1 mM DTT, and 50 ug/mL BSA. The reaction is incubated at 37degC for 30 min. The reaction is stopped, and the amount of radioactivity incorporated into the acid-insoluble fraction (DNA) is measured by liquid scintillation counting. The IC50 is calculated. This assay directly measures the inhibition of DNA polymerase.
|
| Cell Assay |
Cellular assays for Cytarabine 5'-monophosphate are performed on leukemia cell lines. A standard protocol: L1210 mouse leukemia cells or HL-60 human promyelocytic cells are seeded in 96-well plates (10,000 cells/well). Cytarabine (or ara-CMP, the drug is usually ara-C) is added at concentrations ranging from 0.01 nM to 10 uM. The cells are incubated for 48-72 hours. Cell viability is measured using the MTT assay or by counting viable cells using trypan blue exclusion. The IC50 is calculated. A separate set of cells is treated with 10 uM ara-CMP for 4 hours. The cells are lysed, and the DNA is extracted to measure DNA fragmentation (TUNEL assay). A positive TUNEL signal indicates apoptosis. This assay is used to determine the sensitivity of patient leukemia cells to chemotherapy.
|
| Animal Protocol |
In vivo animal experiments for Cytarabine 5'-monophosphate are performed using a mouse leukemia model (L1210). A standard protocol: BDF1 mice (6-8 weeks) are inoculated intraperitoneally (IP) with 1 × 10⁵ L1210 leukemia cells on day 0. Mice are then randomized (n=10/group). Cytarabine (the prodrug, ara-C) is administered IP at doses of 3.5, 7.5, 15, 30, 60, and 75.1 mg/kg/day on days 1, 5, and 9. The control group receives vehicle only. The primary endpoint is the median survival time (days). The percentage increase in life span (%ILS) is calculated: (median survival of treated / median survival of control - 1) × 100. A dose-dependent increase in survival (e.g., > 50% ILS) indicates anti-leukemic activity. The compound can improve the survival rate of leukemia mice.
|
| ADME/Pharmacokinetics |
The pharmacokinetics of Cytarabine 5'-monophosphate is not relevant as a direct drug. The parent drug, cytarabine (ara-C), has poor oral bioavailability (<20%). It is administered intravenously or subcutaneously. It has a short plasma half-life (10-15 minutes) due to rapid deamination by cytidine deaminase in the liver and plasma. To enhance stability, a liposomal formulation (liposomal cytarabine, DepoCyt) has been developed for intrathecal injection to treat leptomeningeal leukemia. The active metabolite, ara-CTP, accumulates inside cells. The compound has a molecular weight of 323.20. It is a solid. It is water-soluble. It is stored at -20degC.
|
| Toxicity/Toxicokinetics |
The toxicology of Cytarabine 5'-monophosphate is well-documented as part of the parent drug cytarabine. The major dose-limiting toxicities of cytarabine are myelosuppression (low white blood cells, platelets, and anemia), which can lead to infections and bleeding. It also causes gastrointestinal toxicity (nausea, vomiting, mucositis), fever (cytokine release), and cerebellar toxicity (dose-dependent, particularly in high-dose regimens). It is teratogenic. It is a vesicant (can cause tissue necrosis if extravasated). Safety precautions: Chemotherapy agents must be handled in a biological safety cabinet (BSC) with full PPE (gloves, gown, mask). It is a cytotoxic drug. It is for research use.
|
| References |
|
| Additional Infomation |
The significance of Cytarabine 5'-monophosphate is its central role in the treatment of acute leukemia. It is the most effective single agent for AML and is a key component of induction and consolidation chemotherapy (e.g., the "7+3" regimen). Its history dates back to the 1960s. The resistance to ara-C occurs via decreased expression of deoxycytidine kinase (dCK), increased cytidine deaminase (CDA), or increased expression of efflux pumps. The compound is used as a reference standard in drug development to test new combinations (e.g., with cladribine or venetoclax). It is not a research chemical for sale to patients. It is an active metabolite. It is a DNA synthesis inhibitor. It is an anti-cancer drug. It is a good apoptosis inducer.
|
| Molecular Formula |
C9H14N3O8P
|
|---|---|
| Molecular Weight |
323.20
|
| Exact Mass |
323.052
|
| CAS # |
7075-11-8
|
| Related CAS # |
Cytarabine-13C3 5'-monophosphate
|
| PubChem CID |
65177
|
| Appearance |
Typically exists as solids at room temperature
|
| Density |
2.15g/cm3
|
| Boiling Point |
678.1ºC at 760 mmHg
|
| Melting Point |
169-174ºC
|
| Flash Point |
363.9ºC
|
| Index of Refraction |
1.774
|
| LogP |
0
|
| Hydrogen Bond Donor Count |
5
|
| Hydrogen Bond Acceptor Count |
8
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
21
|
| Complexity |
531
|
| Defined Atom Stereocenter Count |
4
|
| SMILES |
O=C1N=C(N)C=CN1[C@H]2[C@H]([C@@H]([C@@H](COP(O)(O)=O)O2)O)O
|
| InChi Key |
IERHLVCPSMICTF-CCXZUQQUSA-N
|
| InChi Code |
InChI=1S/C9H14N3O8P/c10-5-1-2-12(9(15)11-5)8-7(14)6(13)4(20-8)3-19-21(16,17)18/h1-2,4,6-8,13-14H,3H2,(H2,10,11,15)(H2,16,17,18)/t4-,6-,7+,8-/m1/s1
|
| Chemical Name |
[(2R,3S,4S,5R)-5-(4-amino-2-oxopyrimidin-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate
|
| Synonyms |
Cytarabine-5'-monophosphate
|
| 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 | 3.0941 mL | 15.4703 mL | 30.9406 mL | |
| 5 mM | 0.6188 mL | 3.0941 mL | 6.1881 mL | |
| 10 mM | 0.3094 mL | 1.5470 mL | 3.0941 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
