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Related Concept Videos

The Proteasome02:18

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
The Proteasome01:13

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 (ubiquitin...
The Proteasome02:18

The Proteasome

Eukaryotic cells can degrade proteins through several pathways. One of the most important amongst these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. A series of enzymes carry out the ubiquitination of the target proteins - E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
The Proteasome Structure01:17

The Proteasome Structure

The ubiquitin-proteasome pathway is a well-known mechanism utilized by eukaryotic cells to remove cytoplasmic proteins that are misfolded, damaged, or no longer needed. In this pathway, the protein that needs to be eliminated undergoes a process called ubiquitination, where a chain of ubiquitin molecules is attached to the 48th lysine residue of the target protein. This ubiquitin modification helps the proteasome distinguish between a target protein and a healthy protein.
The proteasome is an...
Microorganisms in Medicine and Therapeutics01:29

Microorganisms in Medicine and Therapeutics

Microorganisms play a fundamental role in vaccine development, gene therapy, and therapeutic production. Their biological properties are harnessed to advance medicine and public health. Beyond immunization, microorganisms contribute to gut health, antibiotic synthesis, and genetic disease treatment.Live Attenuated and Inactivated VaccinesLive attenuated vaccines, such as the measles, mumps, and rubella (MMR) vaccine, utilize weakened forms of pathogens to closely resemble natural infections.

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High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines
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High-Throughput Cellular Profiling of Targeted Protein Degradation Compounds Using HiBiT CRISPR Cell Lines

Published on: November 9, 2020

Proteases as therapeutics.

Charles S Craik1, Michael J Page, Edwin L Madison

  • 1Department of Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA 94131, USA. craik@cgl.ucsf.edu

The Biochemical Journal
|March 17, 2011
PubMed
Summary
This summary is machine-generated.

Proteases are a promising drug class, with 12 therapies approved by the U.S. Food and Drug Administration (FDA). Their therapeutic applications are expanding beyond cardiovascular disease to include sepsis, inflammation, and more.

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Characterizing Modulators of Protease-Activated Receptors with a Calcium Mobilization Assay Using a Plate Reader
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Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
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Published on: May 15, 2019

Area of Science:

  • Enzymology
  • Pharmacology
  • Drug Development

Background:

  • Proteases are increasingly recognized as a distinct therapeutic class.
  • While historically used for cardiovascular disease, their applications are broadening.
  • The U.S. Food and Drug Administration (FDA) has approved 12 protease therapies, with more in development.

Purpose of the Study:

  • To review the history of proteases as therapeutics.
  • To provide an overview of current clinical applications.
  • To explore strategies for improving and expanding protease-based treatments.

Main Methods:

  • Literature review of proteases in clinical use.
  • Analysis of historical and current therapeutic applications.
  • Discussion of emerging technologies for protease engineering and delivery.

Main Results:

  • Proteases have evolved from plasma fractions to purified products.
  • Established uses include cardiovascular disease; emerging uses include sepsis, digestive disorders, and inflammatory conditions.
  • Ongoing research focuses on understanding protease biology and engineering enzymes for enhanced efficacy.

Conclusions:

  • Proteases represent an established, safe, and effective drug class.
  • Advancements in understanding protease biology and technology will expand their therapeutic potential.
  • Proteases are poised for significant growth as a diverse therapeutic class.