Most Cited Article: Daclatasvir: The First of a New Class of Drugs Targeted Against Hepatitis C Virus NS5A

Daclatasvir: The First of a New Class of Drugs Targeted Against Hepatitis C Virus NS5A

Author(s):

I. Gentile, F. Borgia, N. Coppola, A.R. Buonomo, G. Castaldo and G. Borgia   Pages 1391-1404 (14)

Abstract:

Hepatitis C virus (HCV) infection affects about 160 million people worldwide. It is treated with pegylatedinterferon (peg-IFN) and ribavirin, and in the case of patients affected by genotype 1, also with a protease inhibitor (telaprevir or boceprevir). Despite a good success rate, IFN-based combinations are contraindicated in several patients (e.g. decompensated cirrhosis, patients with psychiatric disorders, severe heart diseases or autoimmune disorders) and are associated with frequent adverse events that ultimately reduce their use. Numerous oral drugs are in an advanced phase of clinical development, and in some cases, in IFN-free combinations. This review focuses on preclinical and clinical data regarding daclatasvir (BMS-790052), which is a highly selective HCV NS5A replication complex inhibitor effective against HCV genotypes 1, 2, 3 and 4. In vitro data show that daclatasvir exerts a very potent antiviral effect against several HCV genotypes. Its pharmacokinetics is optimal and allows once-a-day oral administration. Its adverse event profile is good. Clinical data regarding its efficacy in combination with peg-IFN, ribavirin or other direct antiviral agents are impressive (rates of sustained virological response range between 60% and 100% in treatment-naïve patients). The only drawback of this drug appears to be a relatively low genetic barrier to resistance. In conclusion, daclatasvir, especially in combinations with other antiviral agents, is a very promising drug for the treatment of chronic hepatitis C.

Keywords:

Combination therapy, daclatasvir, hepatitis C virus, Interferon-free, pegylated-interferon, polymerase inhibitors, resistance, ribavirin.

Affiliation:

Department of Clinical Medicine and Surgery (Ed. 18) – University of Naples “Federico II”, via S. Pansini, 5 I-80131 Naples, Italy.

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Recent Trends in the Discovery of Small Molecule Blockers of Sodium Channels Volume 23, Issue 22

Article Details

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Recent Trends in the Discovery of Small Molecule Blockers of Sodium Channels

[ Vol. 23 , Issue. 22 ]

Author(s):

Roberta Gualdani, Maria Maddalena Cavalluzzi and Giovanni LentiniPages 2289-2332 (44)

Abstract:

Voltage-gated sodium channels (VGSC) are responsible for the selective influx of sodium ions in excitable cells. A number of physiological phenomena such as muscle contraction, pain sensation, processing of neuronal information in the brain as well as neuronal regulation of peripheral tissues rely on the activity of these channels. On the other hand, abnormal activity of VGSC are implicated in several pathological processes (e.g., cardiac arrhythmias, epilepsy, and chronic pain) which in some cases (e.g., channelopathies such as myotonias) are linked to specific gene mutations. As a result, VGSC have never stopped attracting the attention of medicinal chemists and the quest for novel drugs to treat these ion channels-associated diseases continues. In this review, VGSC blocking agents reported in the last lustrum are scrutinised with the aim to give a medicinal chemistry perspective on the most interesting compounds classified on the basis of (i) potential therapeutic application, (ii) targeted VGSC isoforms, and (iii) chemical scaffolds. Finally, the clinical potential of selected drug candidates from each chemotype is evaluated by comparing their ligand efficiency metrics. Possible routes for improvement of these preclinical candidates are also discussed.

Keywords:

Biophysics, Channelopathies, Chemotype, Drug discovery, Efficiency metrics, Electrophysiology, Lead compound, Scaffold.

Affiliation:

Università degli Studi di Bari Aldo Moro Dipartimento di Farmacia - Scienze del Farmaco Via E. Orabona 4 70125, Bari, Italy.

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Current Medicinal Chemistry , 23 Issue 21

Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews and guest edited thematic issues written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

Articles from the journal Current Medicinal Chemistry , 23 Issue 21

• Update on Therapeutic Approaches for Rheumatoid Arthritis
• Current Trends on Antipsychotics: Focus on Asenapine
• Biosimilar Filgrastim in Autologous Peripheral Blood Hematopoietic Stem Cell Mobilization and Post-Transplant Hematologic Recovery
• G-Quadruplex Aptamers to Human Thrombin Versus Other Direct Thrombin Inhibitors: The Focus on Mechanism of Action and Drug Efficiency as Anticoagulants
• Human Tuberculosis. III. Current and Prospective Approaches in Anti-Tubercular Therapy
• Pompe Disease and Autophagy: Partners in Crime, or Cause and Consequence?

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Current Medicinal Chemistry, 23 Issue 15

Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews and guest edited thematic issues written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.

Articles from the journal in Current Medicinal Chemistry, 23 Issue 15

• Role of the Receptor Tyrosine Kinase Axl and its Targeting in Cancer Cells
• New Insight into 2-Methoxyestradiol- a Possible Physiological Link between Neurodegeneration and Cancer Cell Death
• Diaryl Urea: A Privileged Structure in Anticancer Agents
• Abscisic Acid: A Phytohormone and Mammalian Cytokine as Novel Pharmacon with Potential for Future Development into Clinical Applications
• Identifying S100B as a Biomarker and a Therapeutic Target For Brain Injury and Multiple Diseases

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