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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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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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Site-targeted drug delivery systems enhance therapeutic efficacy while minimizing systemic toxicity and treatment costs. Unlike conventional methods, these systems ensure precise drug delivery, improving bioavailability and reducing side effects. Targeted drug delivery is classified into three levels. First-order targeting directs drugs to the capillary beds of specific organs or tissues. Second-order targets specific cell types, such as tumor cells, using receptor-mediated interactions.
Site-Targeted Drug Delivery Systems: Polymeric Carriers01:24

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Polymeric carriers enhance targeted drug delivery by increasing efficacy while minimizing off-target effects. These carriers comprise a biodegradable polymeric backbone integrated with functional elements that enable targeting, improve physicochemical properties, and regulate drug release.Targeting MechanismsThe targeting ability of polymeric carriers is mediated by a homing device, which is a molecular recognition component designed to selectively bind to specific tissues or cells. Monoclonal...
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Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
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Modulating drug impact by wrapping target proteins.

Ariel Fernández1, L Ridgway Scott

  • 1Karl F. Hasselman Chair in Engineering, Professor of BioEngineering, Rice University, Department of Bioengineering, Houston, TX 77005, USA. arifer@rice.edu.

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Area of Science:

  • Biochemistry and Molecular Biology
  • Pharmacology
  • Drug Design

Background:

  • Molecular therapies demand precise control over drug specificity.
  • Ligand-target interactions are key to therapeutic efficacy.
  • Novel markers are needed to guide drug design for enhanced selectivity.

Purpose of the Study:

  • To review advances in molecular therapy specificity.
  • To highlight the role of solvent-exposed hydrogen bonds (dehydrons) as markers for ligand-target interactions.
  • To discuss the application of wrapping technology for improving drug specificity.

Main Methods:

  • Analysis of interfacial dehydrons in target-ligand complexes.
  • Assessment of microenvironmental changes upon molecular association.
  • Exploitation of dehydron differences across protein targets for drug redesign.
  • Application of wrapping modifications to existing drugs, including cancer therapeutics.

Main Results:

  • Dehydrons are not conserved across homologous proteins, indicating their role in specificity.
  • Wrapping technology, by analyzing interfacial dehydrons, enhances drug specificity.
  • Redesigned drugs using wrapping technology show improved selectivity.
  • Distance matrices based on dehydron patterns strongly correlate with pharmacologic distances.

Conclusions:

  • Dehydron analysis and wrapping technology offer a broadly applicable strategy for enhancing drug specificity.
  • This approach can lead to molecular therapies with improved efficacy and reduced side effects.
  • The findings suggest a significant advancement in the rational design of targeted therapeutics.