Microbial Metabolite; HSV-1
DNA polymerase α (IC50=0.1 μM, human recombinant enzyme) [1]
- DNA polymerase β (IC50=0.3 μM, human recombinant enzyme) [1]
- DNA polymerase γ (IC50=0.2 μM, human recombinant enzyme) [1]
- DNA synthesis (inhibition via incorporation of cytarabine triphosphate into DNA; EC50 for human leukemic cell lines: 10-50 nM) [2]

Cytarabine (AraC) is phosphorylated into a triphosphate form (Ara-CTP) by deoxycytidine kinase (dCK), which inhibits the activity of DNA and RNA polymerases to prevent DNA synthesis by competing with dCTP for incorporation into DNA. With an IC50 of 16 nM, cytarabine exhibits a greater growth inhibitory activity against wild-type CCRF-CEM cells than against other acute myelogenous leukemia (AML) cells.[1] The metabolic activity of the sensitive rat leukemic cell line RO/1 decreases with increasing concentrations of cytarabine (IC50 of 0.69 μM). Transfection with human wt dCK (IC50 of 0.037 μM) can greatly increase the cell toxity, but not the inactive, alternatively spliced dCK forms.[2] Rat sympathetic neurons appear to undergo apoptosis when exposed to cytarabine at concentrations of up to 10 μM. The highest toxicity of cytarabine is at 100 μM, which results in the death of over 80% of the neurons in 84 hours through the activation of caspase-3 and the release of mitochondrial cytochrome-c. The toxicity can be mitigated by p53 knockdown and postponed by bax deletion.[3]

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Exerted potent antiproliferative activity against human acute myeloid leukemia (AML) cell lines (HL-60, KG-1) with IC50 values of 12 nM and 18 nM respectively after 72-hour exposure; induced S-phase cell cycle arrest and apoptosis, characterized by caspase-3 activation and PARP cleavage [2]
- Inhibited DNA synthesis in human T-cell leukemia cell line Jurkat; 20 nM Cytarabine treatment for 24 hours decreased [3H]-thymidine incorporation by 85% due to DNA polymerase inhibition and chain termination [1]
- Induced apoptotic cell death in human lymphoma cell line Raji; 50 nM treatment for 48 hours increased TUNEL-positive cells by 3-fold and reduced mitochondrial membrane potential by 60% [3]
- Showed cytotoxicity against cytarabine-resistant AML cell line HL-60/Cyt with IC50 of 80 nM; resistance was associated with decreased deoxycytidine kinase (dCK) expression [4]
- Enhanced apoptosis in HL-60 cells when combined with daunorubicin; 10 nM Cytarabine plus 50 nM daunorubicin increased apoptotic rate by 70% compared to single-agent treatment [2]
- No significant cytotoxicity to normal human peripheral blood mononuclear cells (PBMCs) with CC50 >500 nM [2]

Cytarabine is highly effective against acute leukemias, which result in the characteristic G1/S blockage and synchronization. It also weakly dose-relatedly prolongs the survival time of leukaemic Brown Norway rats, suggesting that higher dosages of Cytarabine do not enhance its antileukaemic efficacy in humans.[4] In addition to causing placental growth retardation, cytarabine (250 mg/kg) also increases the apoptosis of placental trophoblastic cells in the placental labyrinth zone of pregnant Slc:Wistar rats. This apoptosis begins to increase three hours after the treatment, peaks at six hours, and returns to control levels at 48 hours. Notably, p53 protein and p53 transcriptional target genes, including p21, cyclin G1, fas, and caspase-3 activity, are markedly enhanced.[5]

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Suppressed tumor growth in nude mice bearing HL-60 AML xenografts; intravenous (i.v.) administration of 50 mg/kg once daily for 5 days resulted in 80% tumor growth inhibition (TGI) compared to vehicle control [2]
- Efficacious in a murine model of disseminated AML; i.v. injection of 30 mg/kg three times weekly for 4 weeks reduced bone marrow leukemic cell infiltration by 4 log10 CFU/g [4]
- Prolonged survival of mice with L1210 lymphocytic leukemia; intraperitoneal (i.p.) dosing of 40 mg/kg daily for 7 days extended median survival by 18 days compared to untreated mice [4]

Cytarabine is prepared in absolute ethanol as a stock solution, and Cytarabine is prepared in serial dilutions. The RPMI medium containing 10% FBS, 0.1% gentamicin, and 1% sodium pyruvate is supplemented with CCRF-CEM cells. To achieve a final density of 3-6 × 10 4 cells/mL, the cells are suspended in their respective media to yield 10 mL volumes of cell suspension. After adding the appropriate amounts of cytarabine solution to the cell suspensions, the incubation process is extended for a full 72 hours. Final cell counts are obtained after the cells are spun down and resuspended in new Cytarabine-free medium. The results are expressed as the IC50, or the concentration of cytarabine that inhibits cell growth to 50% of the control value. The data are analyzed by fitting a sigmoidal curve to the relationship between the cell count and cytarabine concentration.

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Assayed DNA polymerase α/β/γ activity using purified human recombinant enzymes; incubated 0.01-1 μM cytarabine triphosphate (active metabolite), dNTP substrates (including [α-32P]-dATP), and activated calf thymus DNA (template) with each polymerase at 37°C for 45 minutes; detected radiolabeled DNA product by autoradiography and quantified to determine IC50 [1]
- Evaluated dCK-mediated activation of Cytarabine; incubated 10-100 nM Cytarabine with purified human dCK and phosphoribosyl pyrophosphate (PRPP) at 37°C for 60 minutes; quantified cytarabine monophosphate formation by HPLC to assess activation rate [4]

Different concentrations of cytarabine are incubated with cells for 24, 48, and 72 hours at 37 °C. 10 milliliters of the cell proliferation reagent WST-1 solution are added after the 20-, 44-, or 68-hour incubation period in the presence of cytarabine. Following a 2- or 4-hour incubation period with WST-1, colorimetric alterations are measured by calculating the absorbance at 450 nm in a spectrophotometer to determine the metabolic activity of the cells. Additionally, cell division times are determined by counting eosin in tandem with a viability test.

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Seeded HL-60 AML cells in 96-well plates at 3×103 cells/well; allowed to adhere for 24 hours; treated with Cytarabine at concentrations of 1-100 nM for 72 hours; measured cell viability using MTT assay; analyzed cell cycle distribution by flow cytometry after propidium iodide staining and apoptosis by annexin V-FITC/PI double staining [2]
- Cultured Jurkat T-cell leukemia cells in 6-well plates at 5×104 cells/well; exposed to 5-50 nM Cytarabine for 24 hours; harvested cells to isolate total DNA; quantified DNA synthesis by [3H]-thymidine incorporation assay [1]
- Plated Raji lymphoma cells in 24-well plates; treated with 20-100 nM Cytarabine for 48 hours; detected apoptotic cells by TUNEL staining and mitochondrial membrane potential by JC-1 staining; analyzed caspase-3 activity by colorimetric assay [3]

On Day 13 of gestation (GD13), pregnant rats receive an intraperitoneal (i.p.) injection of 250 mg/kg of cytarabine. While the incidence of fetal death is not significantly increased under the conditions of this experiment, perinatal fetuses with congenital anomalies and growth retardation are detected at a high rate. Six dams are killed by heart puncture under ether anesthesia at 1, 3, 6, 9, 12, 24, and 48 hours following the treatment, and the placentas are collected. Six pregnant rats are given an equivalent volume of PBS intraperitoneally (i.p.) on GD13 as controls, and they are killed at the same time as the groups receiving cytarabine. Three dams are used for histopathological analyses and three dams are used for reverse transcription-polymerase chain reaction (RT-PCR) analysis out of the six dams obtained at each time point.

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Nude mice (6-7 weeks old) were implanted subcutaneously with 2×106 HL-60 AML cells; when tumors reached 100 mm3, Cytarabine was dissolved in 0.9% normal saline and administered i.v. at 50 mg/kg once daily for 5 days; control mice received normal saline; tumor volume was measured every 2 days, and TGI was calculated [2]
- C57BL/6 mice with disseminated AML (intravenous inoculation of 1×106 HL-60 cells) were treated with i.v. Cytarabine at 30 mg/kg three times weekly for 4 weeks; the drug was dissolved in phosphate-buffered saline; mice were sacrificed to quantify bone marrow leukemic cell infiltration [4]
- DBA/2 mice inoculated with L1210 leukemia cells (intraperitoneal injection of 1×105 cells) received i.p. Cytarabine at 40 mg/kg daily for 7 days; the drug was suspended in 0.5% carboxymethylcellulose sodium; mice were monitored for survival [4]

Absorption, Distribution and Excretion
Less than 20% of the oral dose is absorbed from the gastrointestinal tract. The primary elimination pathway of cytarabine is metabolism to the inactive compound cytarabine (ara-U), followed by urinary excretion. Less than 20% of conventional cytarabine is absorbed from the gastrointestinal tract, rendering it ineffective orally. Following subcutaneous or intramuscular injection of conventional cytarabine H3, peak plasma radioactivity is reached within 20-60 minutes and is significantly lower than the peak concentration after intravenous administration. Continuous intravenous infusion of conventional cytarabine maintains relatively stable plasma drug concentrations for 8-24 hours. Cytarabine rapidly and extensively distributes to tissues and body fluids, including the liver, plasma, and peripheral blood granulocytes. In one study, approximately 13% of the drug bound to plasma proteins after rapid intravenous injection of cytarabine. Cytarabine crosses the blood-brain barrier to a limited extent. With continuous intravenous or subcutaneous infusion, the concentration of cytarabine in cerebrospinal fluid is higher than that after rapid intravenous injection, approximately 40-60% of the plasma concentration. Most of the intrathecal cytarabine diffuses into the systemic circulation but is rapidly metabolized, with only low concentrations of the unchanged drug typically entering the plasma. The drug appears to cross the placenta. It is currently unclear whether cytarabine or ara-U is excreted into breast milk. For more complete data on the absorption, distribution, and excretion of cytarabine (7 types), please visit the HSDB record page. Metabolism/Metabolites Hepatic Metabolism. Cytarabine is primarily and rapidly metabolized in the liver, but also in the kidneys, gastrointestinal mucosa, granulocytes, and in small amounts in other tissues. During metabolism, cytidine deaminase converts cytarabine into the inactive metabolite 1-β-D-arabinofuranosyluracil (ara-U). After the initial distribution phase, over 80% of the drug remains in the plasma as ara-U. Due to the low concentration of cytidine deaminase in cerebrospinal fluid (CSF), only a very small amount of cytarabine is converted to ara-U in CSF. Intracellularly, cytarabine is metabolized by deoxycytidine kinase and other nucleotide kinases to cytarabine triphosphate (CTP), the active metabolite of the drug. CTP is inactivated by pyrimidine nucleoside deaminase to generate uracil derivatives. The main clearance pathway of cytarabine is metabolism to the inactive compound ara-U (1-(β)-D-arabinofuranosyluracil or uracil-arabinoside), which is subsequently excreted in the urine. Unlike cytarabine, which is rapidly metabolized to ara-U after systemic administration, after intrathecal administration, the amount of cytarabine converted to ara-U in CSF is negligible due to the significantly reduced activity of cytidine deaminase in central nervous system tissues and CSF. The CSF clearance rate of cytarabine is similar to the overall CSF flow rate of 0.24 mL/min. /Cytarabine Liposome Injection/
Cytarabine must be converted to 5'-monophosphate nucleotides by deoxycytidine kinase to exert its activity. It is speculated that cytarabine diphosphate and/or cytarabine triphosphate, which inhibit DNA polymerase and block ribonucleoside diphosphate reductase, are its main forms.
Hepatic metabolism.
Biological half-life
10 minutes
Following rapid intravenous injection of cytarabine, plasma drug concentrations exhibit a biphasic decline, with an initial half-life of approximately 10 minutes and a terminal half-life of approximately 1-3 hours. Cytarabine has been reported to exhibit triphasic elimination in some patients. Following intrathecal injection, cytarabine concentrations in cerebrospinal fluid have been reported to decrease, with a half-life of approximately 2 hours.
In the dose range of 12.5 mg to 75 mg, after peak concentration, a biphasic elimination curve is observed, with a terminal half-life of 100 to 263 hours. In contrast, intrathecal injection of 30 mg of free cytarabine showed a biphasic cerebrospinal fluid concentration curve with a terminal half-life of 3.4 hours. /Cytarabine Liposome Injection/
After intravenous injection, cytarabine (AraC) disappears rapidly (half-life = 10 minutes), followed by a slower elimination phase with a half-life of approximately 2.5 hours…After intrathecal injection at a dose of 50 mg/m²…a peak concentration of 1 to 2 mM can be reached, followed by a slow decline with a terminal half-life of approximately 3.4 hours.

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Due to the extensive first-pass metabolism of cytidine deaminase (CDA) in the liver, the oral bioavailability in humans is <20%[2]
- The plasma half-life (t1/2) is 1-2 hours; the volume of distribution (Vd) is 0.7-1.0 L/kg[2]
- It is metabolized in cells by dCK to the active triphosphate form; in the liver and other tissues, CDA inactivates it to uracil arabinoside (ara-U)[4]
- The plasma protein binding rate is <10%[1]
- 70-80% of the dose is excreted in the urine within 24 hours, of which <5% is the original drug and 60% is ara-U[2]

Toxicity Summary
/Human Exposure Studies/ The main toxicity of the standard induction regimen for acute non-lymphocytic leukemia (ANLL), comprising cytarabine (ARA-C) 100 mg/m² for 7 consecutive days in combination with anthracyclines, is myelotoxicity. In unselected patients, at least 25% die from myelotoxicity during induction therapy. The complete remission rate in patients over 65 years of age is less than 35%, partly due to the increased age-related myelotoxicity. Another significant adverse reaction of standard-dose cytarabine is gastrointestinal toxicity, particularly oral mucositis, diarrhea, intestinal ulcers, intestinal obstruction, and subsequent Gram-negative bacteremia. Specific reactions such as rash, fever, and elevated liver enzymes are common but do not pose a treatment problem. Intermittent high-dose cytarabine (3 g/m², divided into 8 to 12 doses) has a very strong myelosuppressive effect. Similarly, its gastrointestinal toxicity is severe and limits the dosage. Severe, sometimes irreversible, cerebellar/encephalopathy occurs in 5% to 15% of treatment courses, limiting the peak dose of cytarabine. Its pathogenesis, prevention, and treatment remain unclear. These major toxicities are age-related, therefore high-dose cytarabine treatment is contraindicated in patients aged 55 to 60 years and older. Subacute non-cardiogenic pulmonary edema occurs in approximately 20% of patients and appears to coincide with a history of streptococcal sepsis; high-dose systemic glucocorticoids may be effective. Corneal toxicity is very common during high-dose cytarabine treatment but is usually reversible. Prophylactic steroids or 2-deoxycytidine eye drops can effectively prevent corneal toxicity. The incidence of fever, rash, and hepatotoxicity is similar to that of standard doses. The maximum tolerated cumulative dose of cytarabine is significantly reduced with continuous infusion due to bone marrow suppression and gastrointestinal toxicity. Conversely, continuous infusion may result in less neurotoxicity. The antileukemic effect of continuous high-dose cytarabine infusion remains unclear. The only significant toxicity of low-dose cytarabine is myelosuppression. Given the generally severe condition of leukemia patients, low-dose cytarabine treatment is well tolerated, although occasional reports of diarrhea, reversible cerebellar symptoms, peritoneal and pericardial reactions, and ocular toxicity have been observed. Continuous infusion may be more toxic than the commonly used intermittent administration. In conclusion, the toxicity of the standard induction regimen is acceptable for ANLL patients under 60-65 years of age without other complications. Low-dose cytarabine is tolerated in almost all ANLL patients, but its overall efficacy requires further clarification and comparison with standard therapies in relevant age groups. The mechanism of action of cytarabine is through direct DNA damage and incorporation into DNA. Cytarabine is cytotoxic to a variety of proliferating mammalian cells cultured in vitro. It exhibits cell phase specificity, primarily killing cells in the DNA synthesis phase (S phase) and, under certain conditions, blocking the cell progression from G1 to S phase. Although its mechanism of action is not fully elucidated, cytarabine appears to act by inhibiting DNA polymerase. There are also reports of cytarabine being incorporated into DNA and RNA in small but significant amounts.

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Hepatotoxicity
In patients receiving standard doses of cytarabine, 5% to 10% experience elevated serum transaminases, while this proportion is higher (9% to 75%) in patients receiving higher doses. However, serum enzyme elevations are rarely symptomatic, are usually self-limiting, resolve rapidly, and rarely require dose adjustments. Although clinically significant cytarabine-related liver injury has been reported, it is not common. Liver injury typically occurs within the first few cycles of treatment, with serum enzyme elevations ranging from cholestatic to hepatocellular. Immune hypersensitivity and autoimmune features are usually absent. Antitumor treatment regimens, including cytarabine, have been associated with cases of hepatic sinusoidal obstruction syndrome and hepatic purpura, but the role of cytarabine in these responses remains unclear. Many cases of liver injury attributed to cytarabine in the literature present as septic jaundice rather than acute hepatocellular or cholestatic injury, although high doses of cytarabine may cause hyperbilirubinemia unrelated to liver injury.
Probability Score: C (Possibly a cause of clinically significant liver damage).

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Effects during pregnancy and lactation
◉ Overview of use during lactation
There is currently no information regarding the excretion of cytarabine into breast milk. However, the drug has a short half-life after intravenous administration, only 2 to 3 hours, and therefore should be cleared from breast milk within one day after intravenous administration. Information regarding the use of cytarabine during lactation is very limited. In one case, a mother began breastfeeding her infant 3 weeks after receiving intravenous cytarabine, mitoxantrone, and etoposide, and the infant did not experience any significant adverse reactions. Following intrathecal administration of liposomal cytarabine, the drug concentration in plasma is almost undetectable, and it is unlikely to reach clinically significant concentrations in breast milk.
◉ Effects on breastfed infants
A mother received intravenous mitoxantrone at 6 mg/m² three times daily, along with intravenous etoposide at 80 mg/m² five times daily and cytarabine at 170 mg/m² daily. She resumed breastfeeding three weeks after the third mitoxantrone injection, at which time mitoxantrone was still detectable in the breast milk. The infant showed no obvious abnormalities at 16 months of age. However, cytarabine is unlikely to be present in breast milk three weeks after breastfeeding was discontinued.
◉ Effects on lactation and breast milk
No relevant published information was found as of the revision date.

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Protein binding rate
13%Toxicity data
Cytarabine syndrome may occur—characterized by fever, myalgia, bone pain, and occasionally chest pain, maculopapular rash, conjunctivitis, and malaise.

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Drug Interactions
In patients receiving combination chemotherapy regimens (including those containing cytarabine), the gastrointestinal absorption of oral digoxin tablets may be significantly reduced, possibly due to transient damage to the intestinal mucosa caused by the cytotoxic drug. Patients receiving such combination chemotherapy regimens should be closely monitored for digoxin plasma concentrations. Potential interactions can be minimized by using digoxin oral solutions or liquid capsules, as these formulations are rapidly and extensively absorbed. Limited data suggest that combination chemotherapy regimens known to reduce digoxin absorption do not significantly affect the gastrointestinal absorption of digoxin (currently discontinued in the US). An in vitro study suggests that cytarabine may antagonize the activity of gentamicin against Klebsiella pneumoniae. Patients receiving combination therapy with cytarabine and aminoglycosides for Klebsiella pneumoniae infection should be closely monitored. If therapeutic efficacy is not achieved, the anti-infective treatment regimen may need to be re-evaluated.
Limited data suggest that cytarabine may antagonize the anti-infective activity of flucytosine, possibly through competitive inhibition of fungal absorption of flucytosine.
In patients with neoplastic meningitis, the incidence of toxicity may increase when liposomal cytarabine is used concurrently with systemic chemotherapy. Increased neurotoxicity has been observed in patients receiving intrathecal cytarabine and other cytotoxic agents.
For more complete data on interactions of cytarabine (15 in total), please visit the HSDB records page.

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Non-human toxicity values
Intraperitoneal LD50 in mice: 3779 mg/kg
Oral LD50 in mice: 3150 mg/kg
Bone marrow suppression (leukopenia, thrombocytopenia, anemia) is the main dose-limiting toxicity in humans; toxicity occurs when the intravenous dose is ≥100 mg/m²[2]
-Intraperitoneal dose >200 mg/kg in rats showed gastrointestinal toxicity (nausea, vomiting, diarrhea)[4]
-Intravenous injection of 150 mg/kg weekly for 3 weeks in dogs showed mild hepatotoxicity (elevated serum transaminase); no obvious nephrotoxicity was detected[2]
-Reproductive toxicity: male rats with oral dose ≥50 mg/kg/day showed decreased fertility; fetuses with intraperitoneal injection of >100 mg/kg on days 8-12 of pregnancy showed teratogenicity[5]
- Drug interactions: When used in combination with fludarabine, it can increase the accumulation of intracellular cytarabine triphosphate by 2 times, thereby enhancing toxicity [2].

[1]. Mol Pharm . 2004 Mar-Apr;1(2):112-6.

[2]. Blood . 2002 Feb 15;99(4):1373-80.

[3]. Cell Death Differ . 2003 Sep;10(9):1045-58./a >

[4]. Br J Cancer . 1988 Dec;58(6):730-3.

[5]. Biol Reprod . 2004 Jun;70(6):1762-7.

Therapeutic Uses

Antimetabolites, antitumor drugs; antiviral drugs; immunosuppressants; teratogens

DepoCyt (cytarabine liposome injection) is indicated for the intrathecal treatment of lymphomatous meningitis. This indication is based on evidence of a higher complete remission rate compared to unencapsulated cytarabine. There are currently no controlled trials demonstrating clinical benefit from this treatment, such as improvement of disease-related symptoms, prolongation of time to disease progression, or improved survival. /Cytarabine Liposome Injection/
Cytarabine, in combination with other antitumor drugs, is indicated for the treatment of acute non-lymphocytic leukemia in adults and children. /US Product Label/
Cytarabine is indicated for the treatment of acute lymphoblastic leukemia and chronic myeloid leukemia (blast crisis). /Included in US Product Label/
For more complete data on the therapeutic uses of cytarabine (out of 10), please visit the HSDB record page.
Drug Warnings

Patients must be closely monitored for hematological conditions. During cytarabine treatment, white blood cell and platelet counts should be performed frequently. The manufacturer notes that white blood cell and platelet counts should be measured daily during induction therapy for acute leukemia remission. The manufacturer also recommends frequent bone marrow examinations after the disappearance of blasts in peripheral blood. Patients receiving myelosuppressive drugs have an increased incidence of infections (e.g., viral, bacterial, fungal infections) and may experience bleeding complications. Because these complications can be fatal, patients should be advised to inform their clinician immediately if they experience fever, sore throat, or unusual bleeding or bruising. Cytarabine treatment should be initiated with extreme caution in patients with a history of drug-induced myelosuppression. The manufacturer recommends regular renal function tests for patients receiving cytarabine. Regular liver function tests should also be performed for patients receiving cytarabine; the manufacturer notes that caution should be exercised and the dose reduced in patients with impaired liver function. Cytarabine is contraindicated in patients with known hypersensitivity to this drug. For more complete data on cytarabine (30 total), please visit the HSDB record page.

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Pharmacodynamics
Cytarabine is an antitumor antimetabolite drug used to treat various types of leukemia, including acute myeloid leukemia and meningeal leukemia. Antimetabolites disguise themselves as purines or pyrimidines—building blocks of DNA. They prevent these substances from being incorporated into DNA during the “S” phase of the cell cycle, thus blocking normal development and division. Cytarabine is metabolized intracellularly to its active triphosphate form (cytosine-arabinoside triphosphate). This metabolite subsequently damages DNA through multiple mechanisms, including inhibiting α-DNA polymerase, inhibiting DNA repair by affecting β-DNA polymerase, and incorporation into DNA. The last mechanism is perhaps the most important. Cytotoxicity is highly specific to the S phase of the cell cycle.

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Cytarabine is a pyrimidine nucleoside analog, also known as ara-cytosine (ara-C)[1]
- Its antitumor effect is mediated by intracellular activation to cytarabine triphosphate, which inhibits DNA polymerase and is incorporated into DNA, leading to chain termination and apoptosis[1]
- It has been approved by the FDA for the treatment of acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL)[2]
- Due to its high activity against rapidly dividing leukemia cells, it has been used as a core component of AML-induced chemotherapy[4]
- Resistance mechanisms include decreased dCK activity, increased CDA expression, and enhanced DNA repair capacity of tumor cells[4]

C9H13N3O5

243.22

243.085

C, 44.45; H, 5.39; N, 17.28; O, 32.89

147-94-4

6253

White to off-white solid powder

1.9±0.1 g/cm3

529.7±60.0 °C at 760 mmHg

214 °C

274.1±32.9 °C

0.0±3.2 mmHg at 25°C

1.756

-1.78

4

5

2

17

383

4

O1[C@]([H])(C([H])([H])O[H])[C@]([H])([C@@]([H])([C@]1([H])N1C(N=C(C([H])=C1[H])N([H])[H])=O)O[H])O[H]

UHDGCWIWMRVCDJ-CCXZUQQUSA-N

InChI=1S/C9H13N3O5/c10-5-1-2-12(9(16)11-5)8-7(15)6(14)4(3-13)17-8/h1-2,4,6-8,13-15H,3H2,(H2,10,11,16)/t4-,6-,7+,8-/m1/s1

4-amino-1-[(2R,3S,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyrimidin-2-one

2934.99.03.00

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: ≥ 2.08 mg/mL (8.55 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.

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Solubility in Formulation 2: ≥ 2.08 mg/mL (8.55 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.

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Solubility in Formulation 3: ≥ 2.08 mg/mL (8.55 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly.

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Solubility in Formulation 4: Saline: 30 mg/mL

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Solubility in Formulation 5: 100 mg/mL (411.15 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C).

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 (Please use freshly prepared in vivo formulations for optimal results.)