Cladribine
[CAS# 4291-63-8]

Identification

• Classification: Biochemical >> Nucleoside drugs >> Deoxynucleotides and their analogues
• Name: Cladribine
• Synonyms: 2-Chloro-2'-deoxyadenosine
• Protein Sequence: N
• Molecular Formula: C₁₀H₁₂ClN₅O₃
• Molecular Weight: 285.69
• CAS Registry Number: 4291-63-8
• EC Number: 636-978-6
• SMILES: C1[C@@H]([C@H](O[C@H]1N2C=NC3=C(N=C(N=C32)Cl)N)CO)O

Properties

• Solubility: 60 mg/mL (DMSO), <1 mg/mL (water) (Expl.)
• Density: 2.0±0.1 g/cm³, Calc.^*
• Index of Refraction: 1.871, Calc.^*
• Boiling Point: 547.6±60.0 ºC (760 mmHg), Calc.^*
• Flash Point: 285.0±32.9 ºC, Calc.^*

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

Safety Data

• Hazard Symbols: GHS06;GHS07 Dander
• Hazard Statements: H301+H311+H331-H301-H311-H315-H319-H331-H335
• Precautionary Statements: P261-P262-P264-P264+P265-P270-P271-P280-P301+P316-P302+P352-P304+P340-P305+P351+P338-P316-P319-P321-P330-P332+P317-P337+P317-P361+P364-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Specific target organ toxicity - single exposure	STOT SE	3	H335
Acute toxicity	Acute Tox.	3	H331
Acute toxicity	Acute Tox.	3	H311
Eye irritation	Eye Irrit.	2	H319
Acute toxicity	Acute Tox.	3	H301
Skin irritation	Skin Irrit.	2	H315

Discovory and Applicatios

Cladribine is a purine analog that is primarily used as an anticancer and immunosuppressive agent. It is mainly employed in the treatment of certain types of leukemia, including hairy cell leukemia, and is also used for multiple sclerosis under specific conditions. Cladribine exerts its effects by interfering with DNA synthesis and repair, ultimately leading to the death of rapidly proliferating cells. It is classified as a nucleoside analog, which mimics purine nucleotides, leading to the incorporation of faulty molecules into DNA, causing chain termination and the inhibition of further cell division.

The discovery of cladribine dates back to the early 1980s when researchers were exploring purine analogs as potential therapeutic agents for cancer. It was developed as part of a broader effort to design drugs that could specifically target and destroy cancerous cells. The drug was initially synthesized by scientists at the Wellcome Foundation in the United Kingdom and was later evaluated for its potential to treat hematological malignancies. After successful preclinical studies, cladribine was introduced to clinical trials in the 1980s, where it showed significant promise in treating leukemia. It was first approved by the U.S. Food and Drug Administration (FDA) in 1993 for the treatment of hairy cell leukemia.

Cladribine’s application in medicine is primarily focused on the treatment of hematological cancers such as hairy cell leukemia, chronic lymphocytic leukemia (CLL), and T-cell lymphoma. Its ability to target rapidly dividing cells makes it effective against cancerous cells, which proliferate uncontrollably. Cladribine is also used as an immunosuppressive agent in the management of multiple sclerosis (MS). In this context, it is used to reduce the frequency and severity of relapses in patients with the relapsing-remitting form of multiple sclerosis. The drug is typically administered in a cyclic regimen, with courses of intravenous infusion over several days, followed by periods of rest to allow the body to recover.

Cladribine works by mimicking the nucleotides of purine bases, specifically adenosine and guanosine. When incorporated into DNA, it interferes with DNA synthesis and causes DNA strand breaks, leading to cell death. Additionally, cladribine has immunosuppressive properties, reducing the number of lymphocytes, which are key components of the immune system. In patients with multiple sclerosis, this reduction in immune cell activity helps to limit the autoimmune processes that damage the nervous system.

Despite its effectiveness, cladribine is associated with several side effects, which can include myelosuppression (a decrease in the production of blood cells), immunosuppression, and an increased risk of infections. The drug can also cause gastrointestinal symptoms, such as nausea and vomiting, and in some cases, it may result in liver toxicity. As a result, patients receiving cladribine are carefully monitored for these adverse effects. The drug is typically not recommended for use in patients with impaired kidney function due to its renal clearance and potential for accumulation in the body.

In addition to its established use in cancer treatment, ongoing research is exploring the potential of cladribine for other diseases, such as autoimmune disorders and certain viral infections. Its ability to target and reduce the activity of the immune system makes it a candidate for treating conditions that involve immune system dysfunction.

In conclusion, cladribine is a potent purine analog that plays a significant role in the treatment of leukemia, multiple sclerosis, and other immune-mediated conditions. Its discovery and development have provided effective therapeutic options for diseases that were previously difficult to treat. Although its use is associated with certain risks, the benefits of cladribine in controlling malignancies and modulating immune responses have made it an important drug in modern medicine.

References

1987. 2-Chlorodeoxyadenosine: A new nucleoside with activity in lymphoid malignancies. Leukemia Research, 11(12).
DOI: 10.1016/0145-2126(87)90179-7

1998. Cladribine in the treatment of chronic lymphocytic leukemia. Leukemia & Lymphoma, 29(3-4).
DOI: 10.3109/10428199809068561

2024. Cladribine. Reactions Weekly, 2040(1).
DOI: 10.1007/s40278-024-70898-6