Cytosine β-D-arabinofuranoside

Cytosine β-D-arabinofuranoside Cytarabine, also known as cytosine β-D-arabinofuranoside (Ara-C) , is a nucleoside analog and antimetabolite chemotherapy drug. It is a cornerstone in the treatment of acute leukemias and certain lymphomas, functioning by disrupting DNA synthesis in rapidly dividing cancer cells. Chemical Properties CAS Number : 147-94-4 MDL No. : MFCD00066487 Catalog Number : A808710 EINECS : 205-705-9 Molecular Formula : C₉H₁₃N₃O₅ Molecular Weight : 243.22 g/mol Boiling Point : 386.09 °C Melting Point : 214 °C (lit.) Flash Point : 283.8 °C Appearance : White crystalline powder Optical Rotation : D²⁴ +153° (c = 0.5 in water) Refractivity : 1.5100 Storage : Store at 2–8 °C for long-term stability (months). Applications Oncology : Acute Myeloid Leukemia (AML) : Primary use in induction and consolidation therapy, often combined with anthracyclines (e.g., daunorubicin). Acute Lymphocytic Leukemia (ALL) : Integral to treatment protocols for pediatric and adult ALL. Lymphomas : Used in blast-phase chronic myelocytic leukemia and certain non-Hodgkin lymphomas. Antiviral Activity : Limited use in generalized herpesvirus infections due to severe bone marrow suppression and toxicity. Neurological Research : Controls glial cell proliferation in cultures and promotes neuronal differentiation in motor neuron-like cell lines. Mechanism of Action Antimetabolite : Mimics cytidine but substitutes arabinose for deoxyribose, leading to incorporation into DNA during the S phase. DNA Synthesis Inhibition : Converted intracellularly to cytarabine triphosphate (Ara-CTP) , which competitively inhibits DNA polymerase α and β. Causes chain termination and defective DNA repair, selectively targeting rapidly dividing cells. RNA and Enzyme Interference : Inhibits RNA polymerases and ribonucleotide reductase, further blocking DNA synthesis. Administration Intravenous (IV) : Most common route, via central line, PICC line, or cannula. Subcutaneous (SC) : For specific protocols, injected into the stomach, thigh, or arm. Intrathecal (IT) : Directly into cerebrospinal fluid for meningeal leukemia prophylaxis or treatment. Safety Profile Common Side Effects : Hematologic : Severe myelosuppression (neutropenia, thrombocytopenia, anemia). Gastrointestinal : Nausea, vomiting, mucositis, diarrhea. Neurologic : Cerebellar toxicity (ataxia, slurred speech) at high doses. Severe Toxicities : High-Dose Risks : Neurotoxicity (cerebellar dysfunction, seizures), pulmonary edema, corneal toxicity. Rare Complications : Pancreatitis, hepatic dysfunction, palmar-plantar erythrodysesthesia. Clinical Considerations Dose Dependency : Standard Dose : 100–200 mg/m² (induction therapy). High-Dose (HDAC) : 1,000–3,000 mg/m² for refractory/relapsed AML, requiring strict neurotoxicity monitoring. Combination Therapy : Synergizes with anthracyclines, fludarabine, and asparaginase 3 . Citations: https://en.wikipedia.org/wiki/Cytarabine https://pubmed.ncbi.nlm.nih.gov/2031974/ https://pubmed.ncbi.nlm.nih.gov/9218105/ https://go.drugbank.com/drugs/DB00987 https://www.cancerresearchuk.org/about-cancer/treatment/drugs/cytarabine https://www.tandfonline.com/doi/abs/10.3109/03639048909062750 https://ontosight.ai/glossary/term/Arabinoside---ara-C