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Related Concept Videos

Targets for Drug Action: Overview01:26

Targets for Drug Action: Overview

Drugs target macromolecules to modify ongoing cellular processes. Primary drug targets include receptors, ion channels, transporters, and enzymes.
Receptors are either membrane-spanning or intracellular proteins, which upon binding a ligand, get activated and transmit the signal downstream to elicit a response. Drugs bind receptors, either mimicking the action of endogenous ligands or blocking the receptor activity to bring about a modified response. Nearly 35% of approved drugs target the G...
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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:
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Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
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Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
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Direct-acting cholinergic agonists have many therapeutic uses in various medical fields. Choline esters, including acetylcholine, have limited clinical utility due to their non-selectivity and short duration of action. Still, acetylcholine and carbachol are applied topically during ophthalmologic surgery to induce miosis. Pilocarpine, a muscarinic and ganglionic stimulator, effectively treats open-angle glaucoma and alleviates xerostomia and dry mouth caused by radiotherapy or Sjögren syndrome.

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Bromodomains as therapeutic targets.

Susanne Muller1, Panagis Filippakopoulos, Stefan Knapp

  • 1Department of Clinical Medicine, Structural Genomics Consortium, University of Oxford, Oxford, UK.

Expert Reviews in Molecular Medicine
|September 22, 2011
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Summary

Bromodomains (BRDs) are key protein readers of lysine acetylation. Targeting BRDs offers a promising new avenue for drug development in various diseases linked to aberrant acetylation.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Drug Discovery

Background:

  • Lysine acetylation is a crucial post-translational modification regulating cellular signaling and disease.
  • Histone acetyltransferases (HATs) and histone deacetylases (HDACs) are well-studied drug targets, but modulators of the acetylation 'reading process' are scarce.
  • Bromodomains (BRDs) are protein modules that recognize and bind to acetylated lysine residues (K(ac)).

Purpose of the Study:

  • To highlight the therapeutic potential of targeting bromodomains (BRDs) as a novel drug development strategy.
  • To emphasize the role of BRDs in mediating the biological effects of lysine acetylation.
  • To discuss the implications of BRD inhibition in disease contexts.

Main Methods:

  • Review of existing literature on bromodomains, lysine acetylation, and drug development.
  • Analysis of the structural features of BRDs, particularly their acetyl lysine binding sites.
  • Examination of recent studies on BET family BRD inhibitors in disease models.

Main Results:

  • Bromodomains (BRDs) possess druggable binding pockets for small molecules.
  • Targeting BRDs, particularly the BET family, has shown efficacy in preclinical models of inflammation and cancer.
  • Inhibitors of BRDs represent a new class of therapeutics for diseases driven by aberrant acetylation.

Conclusions:

  • Bromodomains (BRDs) are emerging as critical therapeutic targets alongside HATs and HDACs.
  • Targeting BRDs offers a novel approach for treating a wide range of diseases associated with dysregulated lysine acetylation.
  • Further development of BRD inhibitors holds significant promise for pharmaceutical intervention.