Cytarabine
[CAS# 147-94-4]

Identification

• Classification: API >> Antineoplastic agents >> Antimetabolite antineoplastic
• Name: Cytarabine
• Synonyms: Cytosine arabinoside; 4-Amino-1-beta-D-arabinofuranosyl-2(1H)-pyrimidinone; Arabinocytidine
• Molecular Formula: C₉H₁₃N₃O₅
• Molecular Weight: 243.22
• Protein Sequence: N
• CAS Registry Number: 147-94-4
• EC Number: 205-705-9
• SMILES: C1=CN(C(=O)N=C1N)[C@H]2[C@H]([C@@H]([C@H](O2)CO)O)O

Properties

• Solubility: 1 mg/mL (DMSO), 50 mM (water) (Expl.)
• alpha: -129 ° (Expl.)
• Density: 1.9±0.1 g/cm³, Calc.^*
• Index of Refraction: 1.756, Calc.^*
• Boiling Point: 545.7±60.0 °C (760 mmHg), Calc.^*
• Flash Point: 283.8±32.9 °C, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07;GHS08 Dander
• Risk Statements: H317-H340-H360-H361
• Safety Statements: P203-P261-P272-P280-P302+P352-P318-P321-P333+P317-P362+P364-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin sensitization	Skin Sens.	1	H317
Reproductive toxicity	Repr.	2	H361
Reproductive toxicity	Repr.	1B	H360
Germ cell mutagenicity	Muta.	1B	H340
Eye irritation	Eye Irrit.	2	H319
Skin irritation	Skin Irrit.	2	H315
Carcinogenicity	Carc.	2	H351
Specific target organ toxicity - single exposure	STOT SE	3	H335
Skin sensitization	Skin Sens.	1B	H317
Specific target organ toxicity - single exposure	STOT SE	3	H336

Discovery and Applications

Cytarabine, also known as ara-C, is a chemotherapy medication used primarily in the treatment of hematological cancers, including acute leukemia and lymphoma. Its discovery can be traced back to the early 1960s, when it was synthesized by scientists at the Upjohn Company, now part of Pfizer. The compound was derived from cytosine, a naturally occurring nucleic acid base, and its unique structure allowed it to act as an effective antimetabolite, interfering with the synthesis of DNA.

Cytarabine’s mechanism of action is based on its ability to inhibit DNA synthesis. It is a nucleoside analog that is structurally similar to deoxycytidine, a natural component of DNA. After being metabolized inside the body, cytarabine is converted into its active form, ara-CTP, which competes with deoxycytidine triphosphate for incorporation into the DNA strand. Once incorporated, cytarabine disrupts DNA replication, leading to the inhibition of cell division and the eventual death of rapidly dividing cancer cells. This mechanism makes it particularly effective in targeting the cells that characterize leukemia and other cancers of the blood and bone marrow.

Cytarabine is primarily used in the treatment of acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and chronic myelogenous leukemia (CML). It is often administered in combination with other chemotherapy drugs to improve efficacy and reduce the risk of resistance. In addition to its use in leukemia, cytarabine has been employed in the treatment of non-Hodgkin lymphoma, meningeal leukemia, and some solid tumors. It can be administered intravenously or intrathecally, depending on the specific treatment protocol and the type of leukemia being targeted.

Beyond its use as an anticancer agent, cytarabine has also been investigated for potential applications in other diseases. It has shown promise as a neuroprotective agent in certain models of neurodegenerative diseases, such as Alzheimer's disease, though its clinical use in these conditions remains limited. Additionally, cytarabine's ability to cross the blood-brain barrier makes it valuable in treating central nervous system leukemias, where other chemotherapeutic agents may be less effective.

Despite its effectiveness, cytarabine therapy is associated with a number of potential side effects. Common adverse reactions include gastrointestinal disturbances, such as nausea and vomiting, as well as bone marrow suppression, which can lead to anemia, neutropenia, and thrombocytopenia. In addition, high-dose cytarabine is associated with a risk of neurologic toxicity, including cerebellar toxicity, which can cause balance and coordination issues. The use of cytarabine requires careful monitoring of blood counts and the management of side effects.

In conclusion, cytarabine remains a cornerstone in the treatment of acute leukemias and other hematological cancers. Its discovery and development have significantly improved the prognosis for patients with these diseases. Although it is not without its side effects, its effectiveness in targeting rapidly dividing cancer cells has solidified its place as an essential chemotherapeutic agent in oncology.

References

2025. n-3 polyunsaturated fatty acids enhanced efficacy of cytarabine in iron-overloaded NALM-6 cells via apoptotic and oxidative pathways. Toxicology in Vitro, 94, 105976.
DOI: 10.1016/j.tiv.2024.105976

2024. A phase 2 pilot study of umbilical cord blood infusion as an adjuvant consolidation therapy in elderly patients with acute myeloid leukemia. Signal Transduction and Targeted Therapy, 9(1), 317.
DOI: 10.1038/s41392-024-02065-y

2024. Lower-intensity CPX-351 plus venetoclax induction for adults with newly diagnosed AML unfit for intensive chemotherapy. Blood Advances, 8(24), 6729-6738.
DOI: 10.1182/bloodadvances.2024013687