Related Experiment Video
Updated: Aug 7, 2026
05:46
Rapid Screening of HIV Reverse Transcriptase and Integrase Inhibitors
Published on: April 9, 2014
Protease inhibitors in the clinic
Giovanni Abbenante1, David P Fairlie
1Centre for Drug Design and Development, Institute for Molecular Bioscience, University of Queensland, Brisbane, Qld 4072, Australia. d.fairlie@imb.uq.edu.au.
Medicinal Chemistry (Shariqah (United Arab Emirates))
|June 23, 2006
Summary
This review tracks the clinical progress of protease inhibitors, experimental drugs targeting key enzymes. It details 108 inhibitor structures and over 100 drugs in human trials for therapeutic potential.
Area of Science:
- Medicinal Chemistry
- Pharmacology
- Drug Discovery
Background:
- Proteases, specifically peptidases, are crucial enzymes catalyzing polypeptide hydrolysis.
- These enzymes are classified based on their active site catalytic residue (aspartic, serine, cysteine, metallo, threonine).
- Protease inhibitors represent a promising class of therapeutic agents.
Purpose of the Study:
- To review the clinical status of experimental protease inhibitors.
- To update the clinical disposition of over 100 human-trialed inhibitors.
- To assess progress, predict futures, and identify hurdles for protease inhibitor development.
Main Methods:
- Structural analysis of 108 protease inhibitors.
- Compilation and update of clinical trial data for over 100 inhibitors.
- Comparative analysis of current and past (5 years ago) clinical progress.
Main Results:
- Detailed structures for 108 enzyme inhibitors are presented.
- Clinical status updated for over 100 prospective medicines in human trials.
- Progress and challenges in bringing protease inhibitors to the clinic are assessed.
Conclusions:
- Protease inhibitors show significant promise as therapeutic agents.
- Continued research and development are essential to overcome remaining hurdles.
- The field has advanced considerably, with many inhibitors progressing through clinical trials.
Related Concept Videos
01:19Inhibitors of Virion Maturation and Assembly
As part of their replication cycle, certain viruses synthesize long precursor proteins called polyproteins within infected host cells. In human immunodeficiency virus (HIV), two major polyproteins are produced: Gag and Gag-Pol. The Gag polyprotein supplies the structural components of the virus, while Gag-Pol includes essential viral enzymes such as reverse transcriptase, integrase, and protease. After synthesis, these polyproteins move to the host cell membrane, where they assemble into an...
01:22Antiviral Nucleoside Inhibitors
Antiviral Nucleoside InhibitorsAntiviral nucleoside inhibitors are structural analogs of natural nucleosides that interfere with viral DNA or RNA synthesis. These compounds selectively target viral polymerases due to their resemblance to host nucleosides, thereby disrupting viral genome replication.Mechanism of Acyclovir ActionAcyclovir is a guanosine analog with a three-carbon acyclic side chain. It selectively targets herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2),...
01:30Inhibitors of Viral Protein Synthesis
Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
01:23Dipeptidyl Peptidase 4 Inhibitors
Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a significant...
01:21Antiprotozoal Agents
Leishmaniasis is a widespread parasitic disease caused by several Leishmania species. It affects millions of people each year and remains a major public health problem in endemic regions. First-line treatment relies on pentavalent antimonials, including meglumine antimoniate and sodium stibogluconate. Even so, how these drugs work has not been fully clear, especially their interaction with parasite-specific biochemical pathways. One key target is trypanothione reductase (TR), an enzyme that...
01:30Enzyme Inhibition
Inhibitors are molecules that reduce enzyme activity by binding to the enzyme. In a normally functioning cell, enzymes are regulated by a variety of inhibitors. Drugs and other toxins can also inhibit enzymes. Some inhibitors bind to the enzyme’s active site, while others inhibit enzymatic activity by binding to other sites on the protein structure.