Entecavir
[CAS# 142217-69-4]

Identification

• Classification: API >> Synthetic anti-infective drugs >> Antiviral drugs
• Name: Entecavir
• Synonyms: 2-Amino-1,9-dihydro-9-[(1S,3R,4S)-4-hydroxy-3-(hydroxymethyl)-2-methylenecyclopentyl]-6H-purin-6-one
• Molecular Formula: C₁₂H₁₅N₅O₃
• Molecular Weight: 277.28
• CAS Registry Number: 142217-69-4
• EC Number: 604-279-5
• SMILES: C=C1[C@H](C[C@@H]([C@H]1CO)O)N2C=NC3=C2N=C(NC3=O)N

Properties

• Solubility: 10 mM (DMSO) (Expl.)
• Density: 1.8±0.1 g/cm³, Calc.^*
• Index of Refraction: 1.837, Calc.^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H332-H335
• Safety Statements: P261-P280-P305+P351+P338

Discovery and Applications

Entecavir is an antiviral medication primarily used in the treatment of chronic hepatitis B, a viral infection that affects the liver and can lead to severe complications such as cirrhosis, liver failure, and liver cancer. It is classified as a nucleoside reverse transcriptase inhibitor (NRTI) and works by inhibiting the reverse transcriptase enzyme, which is essential for the replication of the hepatitis B virus (HBV). The discovery and application of entecavir have significantly improved the management of chronic hepatitis B, particularly for patients who have developed resistance to other antiviral therapies.

Entecavir was first developed in the late 1990s by Bristol-Myers Squibb and was subsequently approved by the U.S. Food and Drug Administration (FDA) in 2005 for the treatment of chronic hepatitis B infection. The compound was designed to have a high barrier to resistance, which distinguishes it from older antiviral medications. It is a synthetic analog of guanosine, one of the building blocks of DNA, and functions by competing with the natural nucleosides for incorporation into the viral DNA strand during replication. Once incorporated, entecavir causes chain termination, thereby halting the replication process of the hepatitis B virus.

The application of entecavir in clinical settings has proven to be highly effective in reducing HBV viral load, improving liver function, and decreasing the risk of cirrhosis and liver cancer. Studies have shown that entecavir has superior antiviral activity compared to other NRTIs, such as lamivudine, and has a lower likelihood of inducing resistance. This is particularly important in the long-term treatment of chronic hepatitis B, as resistance to antiviral drugs can render treatment less effective. Additionally, entecavir has been shown to be well-tolerated by most patients, with minimal side effects, making it an attractive option for long-term management.

In clinical practice, entecavir is typically administered as a once-daily oral tablet. It is recommended for use in adults with chronic hepatitis B who have evidence of active viral replication and elevated liver enzyme levels. The drug is also used in patients with compromised liver function, including those with cirrhosis, although dose adjustments may be required in individuals with renal impairment. Due to its efficacy and low resistance profile, entecavir is considered a first-line treatment for chronic hepatitis B and is often preferred over older therapies.

One of the key challenges in the treatment of hepatitis B is the potential for resistance to antiviral medications. Although entecavir has a high barrier to resistance, patients with long-term exposure to the drug may still develop mutations in the HBV genome that reduce its effectiveness. As a result, ongoing research is focused on optimizing treatment regimens and developing newer antiviral agents that can offer even greater efficacy and resistance profiles.

In conclusion, entecavir is a potent antiviral agent that has significantly advanced the treatment of chronic hepatitis B. Its discovery and subsequent application have provided patients with a more effective and safer treatment option compared to older antiviral drugs. With its high barrier to resistance and favorable safety profile, entecavir has become an essential tool in the management of chronic hepatitis B, improving patient outcomes and reducing the long-term risks associated with the infection.

References

2014. Optimal therapy of chronic hepatitis B: how do I treat HBeAg-positive patients?. Liver International: Official Journal of the International Association for the Study of the Liver, 35(1).
DOI: 10.1111/liv.12719

2012. Bioequivalence Evaluation of 2 Tablet Formulations of Entecavir in Healthy Chinese Volunteers: A Single-Dose, Randomized-Sequence, Open-Label Crossover Study. Arzneimittel-Forschung, 62(3).
DOI: 10.1055/s-0031-1297964

2009. Use of the Novel INNO-LiPA Line Probe Assay for Detection of Hepatitis B Virus Variants That Confer Resistance to Entecavir Therapy. Journal of Clinical Microbiology, 47(2).
DOI: 10.1128/jcm.01678-08